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Developmental conversion of thymocyte-attracting cells into self-antigen-displaying cells in embryonic thymus medulla epithelium
Get PDFThymus medulla epithelium establishes immune self-tolerance and comprises diverse cellular subsets. Functionally relevant medullary thymic epithelial cells (mTECs) include a self-antigen-displaying subset that exhibits genome-wide promiscuous gene expression promoted by the nuclear protein Aire and that resembles a mosaic of extrathymic cells including mucosal tuft cells. An additional mTEC subset produces the chemokine CCL21, thereby attracting positively selected thymocytes from the cortex to the medulla. Both self-antigen-displaying and thymocyte-attracting mTEC subsets are essential for self-tolerance. Here, we identify a developmental pathway by which mTECs gain their diversity in functionally distinct subsets. We show that CCL21-expressing mTECs arise early during thymus ontogeny in mice. Fate-mapping analysis reveals that self-antigen-displaying mTECs, including Aire-expressing mTECs and thymic tuft cells, are derived from CCL21-expressing cells. The differentiation capability of CCL21-expressing embryonic mTECs is verified in reaggregate thymus experiments. These results indicate that CCL21-expressing embryonic mTECs carry a developmental potential to give rise to self-antigen-displaying mTECs, revealing that the sequential conversion of thymocyte-attracting subset into self-antigen-displaying subset serves to assemble functional diversity in the thymus medulla epithelium.journal articl
大学教養教育におけるESD講義の実施と意識変容の検証 : 受講者アンケートの分析
Get PDF徳島大学教養教育院で開講中の講義「地球環境問題」では，人口問題，食料問題，資源エネルギー問題，環境問題の4 つのテーマを取り上げ，地理学的視点からグローバルな危機と対応について考察する力を身につけることを目標としている。2021 ～ 23 年度の受講者を対象とし，持続可能な開発のための教育（ESD）の成果を検証するため，授業開始前と終了後にアンケート調査を実施した。その回答データをもとに，ESD が目指す構成概念である公平性，連携性，責任性に関する意識にいかなる変化が生じたか検証する。受講者はもともと地球環境問題への関心が高い傾向にあり，授業期間中に上記の概念および将来の希望に関する肯定的な意見が増加した。因子分析の結果，授業前は問題意識が曖昧だったが，授業後は批判的考察や主体的取り組みに関する因子が明確に表れた。受講者は授業を通じ問題の複雑さや利害の対立について学び，自己の意見や主張を獲得しえたことがわかる。The course "Global Environmental Problems" offered at Tokushima University’s Institute of Liberal Arts and Sciences aims to develop the ability to consider global crises and countermeasures from a geographical perspective. It covers four topics: population problems, food problems, resource and energy problems, and environmental pollution. To verify the results of Education for Sustainable Development (ESD), a questionnaire survey was conducted before and after the course in 2021-2023. Based on the response data, we have examined the changes in awareness of equality, cooperation, and responsibility, which are the constituent concepts of ESD. The participants have had a high level of interest in global environmental issues. Their positive opinions about these concepts and future aspirations increased during the course. Factor analysis shows that their awareness of the issues was vague before the course, but critical reflection and proactive engagement became clear after the course. These changes may indicate that participants learned not only about the complexity of the issues but also about conflicts of interest and were able to develop their own opinions and arguments.departmental bulletin pape
新たなキャリアモデルの獲得が大学生の進路選択期待とキャリア・パースペクティブに及ぼす影響について
Get PDF本稿では，キャリアモデルを新たに獲得することが大学生の進路選択期待（①進路選択セルフ・エフィカシー(CDMSE) と，②進路選択に対する結果期待）と，キャリア・パースペクティブに及ぼす影響について確認した。その確認のために，大学1年生，2年生を対象にしたパネル調査を実施した。調査の結果，キャリアモデルを新たに獲得すると，（1）学生の進路選択に対する結果期待とキャリア・パースペクティブには影響しないが，（2）学生のCDMSE には影響することが分かった。This study examines the effects of finding new career role models on (1) outcome expectancy for career decision-making, (2) career perspective, and (3) career decision-making self-efficacy (CDMSE) of undergraduate students. This study analyzed data collected through a panel survey with two-way ANOVA with replication. The results clarified the following: (1) finding new career role models did not enhance undergraduate students’ outcome expectancy for career decision making and career perspective, and (2) finding new career role models enhanced undergraduate students’ CDMSE, however.departmental bulletin pape
寒川エコノミックガーデニングの事例に関する一考察
Get PDF地域経済の持続的成長における成功事例の1 つとして、アメリカのコロラド州リトルトン市で編み出された「エコノミックガーデニング」が挙げられる。リトルトン市ではエコノミックガーデニングの導入により税収の増加、雇用の創出等経済成長を促進させ、地域経済社会の危機的状況を乗り越えたといわれている。リトルトン市が策定したエコノミックガーデニング政策は、「企業家精神に溢れた地元中小企業は持続可能な富と新規雇用の創出の原動力であり、わが市の役割はこれらの中小企業が活躍できる環境を創り出すことである」というシンプルな信念に基づいている。
このようなエコノミックガーデニングは、アメリカのみならず、日本の地方自治体においても同様に導入されてきた。地方都市としては徳島県の鳴門市がいち早く導入に至ったといわれているが、導入から10 年経った現在においても著しい成果は上がっていないように見受けられる。鳴門市の他にいち早くエコノミックガーデニングを導入した地方自治体として、鳴門市と類似の人口規模や産業構造の神奈川県高座郡寒川町がある。寒川エコノミックガーデニングの特徴は、産業振興の柱として、製造業の活性化、特に中小企業に特化したものとなっている。
このように行政主導により支援対象を限定した取り組みを促進させている自治体は全国的にも類例が無いのではないかと考える。また、「地域経済コンシェルジュ」というキーパーソンが運営主体となって活躍している。地域経済コンシェルジュは、企業との信頼関係の構築を核とした企業ニーズの掘り起こしと徹底した伴走支援を促進させ、行政と企業等の連結環として機能することで、新たに地域経済を担うであろう優良な中小企業を創出している。本稿では、地域経済コンシェルジュを核とした徹底的な伴走型の企業支援の取り組みを促進させている寒川エコノミックガーデニングの取り組みについて調査した。徹底的な伴走型の企業支援の取り組みは、信頼、繋がりというソーシャル・キャピタルを背景として、寒川町に経済的便益をもたらすものであることが明らかとなった。departmental bulletin pape
Involvement of α-klotho in growth hormone (GH) signaling
Get PDFGrowth hormone (GH) exerts multiple effects on different organs directly or via its main mediator, insulin-like growth factor1 (IGF1). In this study, we focused on the novel relationship between GH action and the antiaging hormone α-klotho. Immunofluorescent staining of α-klotho was observed in the renal distal tubules and pituitary glands of somatostatin- and GH-positive cells in wild-type (WT) mice. Treatment of 4-week-old WT mice with GH increased IGF1 mRNA expression in the pituitary gland, liver, heart, kidney, and bone but increased α-klotho mRNA expression only in the pituitary gland, kidney, and bone. Increased α-klotho protein levels were observed in the kidney but not in the pituitary gland. No induction of α-klotho RNA expression by GH was observed in juvenile mice with kidney disease, indicating GH resistance. Furthermore, GH and α-klotho supplementation in HEK293 cells transfected with GHR increased Janus kinase 2 mRNA (a GH downstream signal) expression compared to supplementation with GH alone. In conclusion, we suggest that 1) the kidney is the main source of secreted α-klotho, which is detected in blood by the downstream action of GH, 2) α-klotho induction by GH is resistant in kidney disease, and 3) α-klotho might be an enhanced regulator of GH signaling.doctoral thesi
Respiratory tract barrier dysfunction in viral-bacterial co-infection cases
Get PDFA preceding viral infection of the respiratory tract predisposes the host to secondary bacterial pneumonia, known as a major cause of morbidity and mortality. However, the underlying mechanism of the viral-bacterial synergy that leads to disease progression has remained elusive, thus hampering the production of effective prophylactic and therapeutic intervention options. In addition to viral-induced airway epithelial damage, which allows dissemination of bacteria to the lower respiratory tract and increases their invasiveness, dysfunction of immune defense following a viral infection has been implicated as a factor for enhanced susceptibility to secondary bacterial infections. Given the proximity of the oral cavity to the respiratory tract, where viruses enter and replicate, it is also well-established that oral health status can significantly influence the initiation, progression, and pathology of respiratory viral infections. This review was conducted to focus on the dysfunction of the respiratory barrier, which plays a crucial role in providing physical and secretory barriers as well as immune defense in the context of viral-bacterial synergy. Greater understanding of barrier response to viral-bacterial co- infections, will ultimately lead to development of effective, broad-spectrum therapeutic approaches for prevention of enhanced susceptibility to these pathogens.journal articl
Activation of Janus kinase 2 contributes to the autoimmune pathology in the salivary glands of patients with Sjögren's syndrome
Get PDFAim: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease that affects exocrine glands. CXCL10 production from salivary gland ductal cells via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway has been suggested to be involved in glandular inflammation in pSS. We aimed to investigate JAK1, JAK2, phosphorylated JAK1, and phosphorylated JAK2 expression in labial salivary gland (LSG) tissues from patients with pSS to evaluate the potential of JAK inhibitors as therapeutic agents for pSS.
Methods: Immunohistochemical analysis was performed using LSG tissues of patients with pSS (n = 10), non-SS patients (n = 5), and healthy controls (n = 5). The LSG sections were scored to determine the expression levels of JAK1, JAK2, phosphorylated JAK1, and phosphorylated JAK2 in the ductal and acinar epithelium.
Results: In acinar epithelial cells of LSG tissues, JAK1, JAK2, and phosphorylated JAK1 expression was significantly lower in patients with pSS than in the controls. Significantly high expression of phosphorylated JAK1 and phosphorylated JAK2 was observed in the ductal epithelial cells of patients with pSS. However, there was no significant association between phosphorylated JAK1 or JAK2 expression levels and inflammation degree. Furthermore, immunofluorescence analysis revealed JAK2 phosphorylation in many CD3+ T cells infiltrating the LSG tissues.
Conclusions: The results suggest JAK2 activation in both ductal epithelial cells and infiltrating CD3+ T cells in LSG tissues of patients with pSS. JAK inhibitors may be effective therapeutic agents for pSS by regulating both chemokine production from salivary gland cells and effector T cell activation.journal articl
Action of GABAB receptor on local network oscillation in somatosensory cortex of oral part : focusing on NMDA receptor
Get PDFThe balance of activity between glutamatergic and GABAergic networks is particularly important for oscillatory neural activities in the brain. Here, we investigated the roles of GABAB receptors in network oscillation in the oral somatosensory cortex (OSC), focusing on NMDA receptors. Neural oscillation at the frequency of 8–10 Hz was elicited in rat brain slices after caffeine application. Oscillations comprised a non-NMDA receptor-dependent initial phase and a later NMDA receptor-dependent oscillatory phase, with the oscillator located in the upper layer of the OSC. Baclofen was applied to investigate the actions of GABAB receptors. The later NMDA receptor-dependent oscillatory phase completely disappeared, but the initial phase did not. These results suggest that GABAB receptors mainly act on NMDA receptor, in which metabotropic actions of GABAB receptors may contribute to the attenuation of NMDA receptor activities. A regulatory system for network oscillation involving GABAB receptors may be present in the OSC.doctoral thesi
