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Critical Role of microRNA-33a/b in Cardiovascular and Metabolic Disease: Molecular Mechanisms and Therapeutic Perspectives
No full textMicroRNAs (miRNAs) serve as fundamental post-transcriptional regulators of gene expression, among which the miR-33 family, consisting of miR-33a and miR-33b, has emerged as a critical modulator in the pathogenesis of cardiovascular and metabolic diseases. These miRNAs are embedded within the intronic regions of genes and play pivotal roles in cholesterol homeostasis, fatty acid metabolism, and inflammatory regulation. Notably, miR-33a is highly conserved across various species, whereas miR-33b is found primarily in primates and some other mammals, complicating the development of relevant animal models. These miRNAs inhibit their target genes involved in cholesterol metabolism, fatty acid oxidation, and insulin signaling, consequently influencing the development and progression of cardiovascular and metabolic diseases. Inhibition or genetic ablation of miR-33 has shown therapeutic potential, improving dyslipidemia, atherosclerosis, and metabolic dysfunction-associated steatotic liver disease, through altered cholesterol metabolism, attenuation of inflammation, and increased fatty acid utilization. In addition, miR-33 suppression has been shown to promote skeletal muscle regeneration. However, systemic inhibition of miR-33 requires caution due to the role of miR-33 in hunger signaling and sympathetic nerve activity in the central nervous system, which may lead to obesity. Therefore, the development of tissue-specific strategies is essential for the safe and effective therapeutic targeting of miR-33
Numerical investigation on effect of acetone droplets injection on acetone/methane/air laminar wall-stagnant flames
No full textThe initial phase of fuel, either gaseous or as liquid droplets, is known to affect spray combustion. However, its precise impact on laminar flame speed (L) and thermo-diffusive stability under various strain rates is not fully understood. This study investigates the effect of acetone’s initial phase (gaseous vs. liquid droplets) on the behavior of acetone/methane/air laminar wall-stagnant flames. Two-dimensional numerical simulations using an Eulerian-Lagrangian framework are performed. The global equivalence ratio (Φg) is varied from 0.85 to 1.30, and the Sauter Mean diameter (SMD) of 1.0 and 4.7 μm is applied. Variations in L are analyzed with respect to the droplet’s evaporation, strain rates (K), the effective Lewis number (eff), and the flame stretch sensitivity. The results reveal distinct differences between gaseous and droplet cases, showing good qualitative and quantitative agreement with previous experiments. For liquid acetone droplet cases, L is lower than the corresponding gaseous cases under lean and stoichiometric conditions, but relatively higher under rich conditions. Moreover, in rich droplet cases, L decreases with increasing K. This indicates that the flame stretch sensitivity is negative in rich acetone droplet cases, while it is positive under lean and stoichiometric conditions. These trends are explained by the combined effects of evaporative cooling and changes in eff caused by droplet evaporation
Microcondensate-Mediated Intracellular Infusion of mRNA Across the Plasma Membrane
No full textThis study presents a strategy for developing micrometer-sized coacervates comprised of cationic intracellular delivery peptide FcB(L17E)₃ and nucleic acids (termed "microcondensates") as a lipid nanoparticle (LNP)-free platform for intracellular messenger RNA (mRNA) delivery. The feasibility of this approach is demonstrated both in vitro and in vivo. This approach is based on our previous finding that FcB(L17E)₃ forms a microcondensate through interactions with IgG labeled with a negatively charged fluorescent dye. Similarly, the negative charge of nucleic acids causes siRNAs to form microcondensates with FcB(L17E)₃, resulting in the facile infusion of the siRNAs through the plasma membrane with 40% gene knockdown efficiency. mRNAs form aggregates with FcB(L17E)₃ due to their longer chains, which prevents efficient delivery. Remarkably, adding short single-stranded DNA (ssDNA) to mRNA enables microcondensate formation with FcB(L17E)₃, facilitating protein expression. Additionally, this microcondensate system successfully facilitated the intracellular delivery of plasmid DNA (pDNA) by optimizing the charge ratio between FcB(L17E)₃ and nucleic acids. Finally, the subcutaneous injection of microcondensates into mice successfully induced protein expression in vivo. The achievement of in vivo mRNA delivery and protein expression using microcondensates may offer a strategy for nucleic acid delivery with potential applicability in cancer immunotherapy and mRNA-based vaccination
A Theoretical Study of “Unassumability” and the Continuity of Practice in Clinical Pedagogy: Reconstructing the Concepts of Ecological Conscientisation and Judgment
No full text本文ファイルを差し替え（2026-01-23）本研究は、教育実践において繰り返し生起する「理解されているにもかかわらず引き受けられない経験」および「判断が下されていないように見えながら、実践が継続されている状況」に着目し、これらを欠如や停滞としてではなく、臨床教育学的経験構造として理論化することを目的とする。従来の教育学研究、とりわけ環境教育や批判的教育学においては、意識化は批判的理解から行為へと至る過程として理解されることが多く、行動や成果に結実しない経験の位相は十分に理論化されてこなかった。また、教育実践における判断についても、意思決定や評価の枠組みの中で扱われることが多く、制度的制約下で実践を継続するための過程としては十分に検討されてこなかった。本研究は、これらの課題に対して臨床教育学的視座から応答するため、理論研究として概念再構成という方法を採用する。第一に、フレイレの意識化概念を臨床教育学的に再読し、行動や成果に回収されない関係の揺らぎとして〈エコロジカルな意識化〉概念を再構成する。第二に、教育実践における〈判断〉を、評価や意思決定とは異なる、実践を継続するための臨床的プロセスとして再定義する。第三に、これら二つの概念を統合することにより、教育実践を揺らぎ―判断―継続という循環的構造として理論的に提示する。本研究は、教育実践を成果や行動によってのみ測定する理解に対して理論的修正を加え、揺らぎや未完了性を内包したまま続く営みとして捉え直す理論的基盤を提示する点に学術的意義を有する。This study seeks to theorise educational experiences in which individuals understand an issue yet find it difficult to fully assume it as part of their own practice, as well as situations in which practice continues despite the absence of clearly articulated decisions. Rather than treating such experiences as deficiencies or stagnation, the study conceptualises them as constitutive structures of educational practice from the perspective of clinical pedagogy. In previous educational research, particularly in environmental education and critical pedagogy, conscientisation has often been understood as a process leading from critical understanding to action. Consequently, experiences that do not culminate in visible behavioural change have remained theoretically underexplored. Similarly, judgment in educational practice has typically been framed in terms of decision-making or evaluation, leaving insufficient attention to the processes through which practitioners sustain their practice under institutional constraints. To address these limitations, this study adopts a theoretical approach based on conceptual reconstruction within the framework of clinical pedagogy. First, it re-examines Paulo Freire's concept of conscientisation and reconstructs it as ecological conscientisation, understood as a process characterised by the destabilisation of relationships between the subject and the environment, rather than as a precursor to action. Second, it reconceptualises judgment as a clinical process through which practitioners continually reconfigure their mode of engagement in order to sustain practice, rather than as a discrete act of decision or evaluation. Third, by integrating these two concepts, the study presents educational practice as a cyclical structure in which relational destabilisation and judgment mediate the ongoing continuity of practice. By shifting attention away from outcomes and behavioural change towards the unfinished, relational, and processual nature of educational practice, this study provides a theoretical foundation for understanding practice as an ongoing clinical engagement that endures through uncertainty and unresolved experience
Efficient Penetration of Terbinafine into Brain Abscesses in a Lung Transplant Recipient with Scedosporiosis: A Short Communication
No full textBackground: spp. typically infect the lungs and can disseminate to various tissues, including the central nervous system (CNS). Voriconazole and terbinafine are both used to treat scedosporiosis. While voriconazole has been reported to have good CNS permeability, the permeability of terbinafine in humans remains unclear.Methods: The authors describe a case of infection with brain abscesses in a lung transplant recipient treated with voriconazole and terbinafine. Drug concentrations were measured in the biopsied brain abscess, the surrounding normal cerebrum, serum, and cerebrospinal fluid (CSF). Brain-to-serum and CSF-to-serum partition coefficients for each drug were calculated based on serum concentrations estimated at the time of abscess biopsy and lumbar puncture using population pharmacokinetic models.Results: Trough serum concentrations of voriconazole and terbinafine were 6.28 mcg/mL and 0.41 mcg/mL, respectively. Seven hours after administration, the concentrations in cerebrum were 5.65 mcg/mL and 0.85 mcg/mL, respectively, and those in brain abscess were 4.05 mcg/mL and 1.06 mcg/mL, respectively. The estimated brain-to-serum partition coefficients were 0.730 for voriconazole and 0.553 for terbinafine, indicating substantial penetration of both drugs into the infected tissue. The brain abscess size decreased in this case, suggesting a therapeutic antifungal effect of these agents. However, the measured CSF concentrations at 5 hours postdose were 2.69 mcg/mL for voriconazole and <0.002 mcg/mL for terbinafine. The CSF-to-serum partition coefficients were 0.365 for voriconazole and <5.64 × 10⁻⁴ for terbinafine, indicating poor CSF permeability of terbinafine.Conclusions: These findings suggest that terbinafine has the potential to treat fungal infections within the brain, but may be less effective for CSF infections. Further studies are warranted to clarify incorporation of these agents into CNS infection treatment strategies
Chimeric synthetic T cell receptor and antigen receptor receptors enable high-sensitivity T cell receptor-negative CD8αβ-CD3-positive T-cell development from human-induced pluripotent stem cells
No full textInduced pluripotent stem cell (iPSC)-derived T cells hold great promise for scalable and standardized allogeneic immunotherapies but face critical challenges in differentiation, antigen sensitivity and inaccessibility to intracellular tumor-associated antigens, particularly when engineered with chimeric antigen receptors (CARs). Here, we introduce iPSC with synthetic T cell receptor (TCR) and antigen receptor (STAR) structure, which fuses a single-chain variable fragment (scFv) to the constant regions of TCRαβ. Using a Wilms tumor 1 (WT1)-specific STAR construct, we demonstrate that STAR-iPSC-derived T cells (STAR-iT cells) restore CD3 expression to levels similar to TCR, thereby supporting efficient CD8αβ⁺ CD3⁺ iPSC-T cell development in the absence of TCR. STAR-iT cells exhibit superior antigen sensitivity compared to CAR-based counterparts. STAR-iT cells display robust cytotoxicity against WT1-expressing tumor cells, enhanced cytokine production and efficient expansion. Our findings establish STAR as a scFv-based, next-generation chimeric receptor format and advance the development of universal, off-the-shelf iT cell immunotherapies
[Book Reviews] Iwamoto Masaaki. Vann Molyvann: The Life of a Modern Cambodian Architect. Tokyo: millegraph, 2025, 333p.
No full textWhole Mitochondrial Genome Analysis of Killer Whales Reveals the Presence of Resident and Transient Ecotypes Around Hokkaido
No full textKiller whale communities near Hokkaido: New genomic data on western North Pacific orcas illuminates habitat differences. 京都大学プレスリリース. 2025-12-26.In the North Pacific, there are at least three genetically different ecotypes of killer whales (Orcinus orca), referred to as resident, offshore, and transient. A previous study suggested that killer whales around Hokkaido belong to fish-eating (resident and/or offshore ecotypes) and mammal-eating (transient ecotype) groups. These results were supported by haplotypes based on the combination of 1193 bp of cytochrome b and 420 bp of the control region in mitochondrial genomes. However, this analysis was not sufficient to discriminate between resident and offshore ecotypes because of the short sequence lengths. In this study, we analyzed whole mitochondrial genomes of 25 killer whales sampled around Hokkaido to clarify the ecotypes and mitochondrial genome haplotypes. Phylogenetic analysis revealed the presence of resident and transient ecotypes around Hokkaido. The whales identified as residents shared an identical haplotype, which is the most common haplotype in the western North Pacific. In contrast, the transients around Hokkaido exhibited eight haplotypes, including seven novel ones among the 19 individuals, and their haplotype richness was the highest among the North Pacific populations. This result suggests that the Hokkaido coast served as a refugium for transient killer whales during the Last Glacial Maximum
Arkadien oder Dschinnistan --Wielands Geschichtsphilosophie in Pervonte und sein Bild des Orients--
No full text本論は、本論筆者による博士論文『18世紀クンスト・メルヒェンにおける想像力論の実践と展開 --ヴィーラント・ゲーテ・ノヴァーリスの三者を中心に』 (京都大学大学院、2024年) の第一部第三章「『ペルヴォンテ』における歴史哲学と『ジンニスタン』におけるアルカディアの転換」を加筆・修正したものである。Das deutsche Kunstmärchen Pervonte (1779/96) ist C. M. Wielands freie Bearbeitung des italienischen Märchens Peruonto aus Giambattista Basiles Pentamerone (1634/36). Die größte Änderung, die Wieland vornahm, betrifft den Ausgang der Geschichte. Während Peruonto wie eine Komödie schließt, ist das Ende von Pervonte eher tragisch. Resignierend sagt Vastola, die Prinzessin Salernos: „Auch du warst in Arkadia!“ Das ist nicht nur Ausdruck der Trauer über ihr verlorenes Glück, sondern spricht auch ein geschichtsphilosophisches Thema an. Arkadien, ein klassischer Topos für das goldene Zeitalter, erscheint in Pervonte als nicht mehr erreichbarer Ort und als eine nie wiederkehrende Vergangenheit. Diese pessimistische Geschichtsauffassung unterscheidet sich grundlegend von der in Dschinnistan (1786-1789), einer von Wieland herausgegebenen Märchensammlung. Dort haben viele der Geschichten ein gutes Ende, meist in einer schönen arkadischen Landschaft. Aber das ist nicht der einzige Unterschied. „Dschinnistan“ bedeutet „Land der Dschinn“, die in der Glaubenswelt des Islam Dämonen oder Naturgeister (Feen) sind. In Wielands Adys und Dahy, einem der Märchen in Dschinnistan, wird dieses Land als „Nachbild des irdischen Paradieses“ beschrieben. An die Stelle des abendländischen Arkadiens, dem idealen Ort des goldenen Zeitalters, tritt also mit Dschinnistan ein in der orientalischen Kultur angesiedelter Ort der Vollkommenheit. Daran wird deutlich, dass Wieland in Adys und Dahy den späteren Romantikern sehr nahe steht. Die Sehnsucht nach einem verklärten Bild des Orients, das so oft in den Märchen der Romantik begegnet, findet sich schon in Dschinnistan. Darüber hinaus deutet sich hier bereits die triadische Geschichtsphilosophie von Romantikern wie Novalis an
第一回バイオミメティクス・シーズ研究会要旨集2026 --生物における工学的側面の探求--
No full text第一回バイオミメティクス・シーズ研究会日時 : 2026年2月12日 (木) 13:00-17:00会場 : 京都大学総合博物館 講演室主催 : バイオミメティクス・シーズ研究会 (京都大学地球環境学堂 橘悟、京都大学生命科学研究科 西川星也)運営補助 : 中橋和甫 (京都大学農学部)チラシイラスト・デザイン : 田中花音1st Biomimetics Seeds MeetingBiomimetics Seeds Research Grou