High-endothelial cell-derived s1p regulates dendritic cell localization and vascular integrity in the lymph node

While the sphingosine-1-phosphate (S1P)/sphingosine-1-phosphate receptor-1 (S1PR1) axis is critically important for lymphocyte egress from lymphoid organs, S1PR1-activation also occurs in vascular endothelial cells (ECs), including those of the high-endothelial venules (HEVs) that mediate lymphocyte immigration into lymph nodes (LNs). To understand the functional significance of the S1P/S1PR1-Gi axis in HEVs, we generated Lyve1;Spns2Δ/Δ conditional knockout mice for the S1P-transporter Spinster-homologue-2 (SPNS2), as HEVs express LYVE1 during development. In these mice HEVs appeared apoptotic and were severely impaired in function, morphology and size; leading to markedly hypotrophic peripheral LNs. Dendritic cells (DCs) were unable to interact with HEVs, which was also observed in Cdh5CRE-ERT2;S1pr1Δ/Δ mice and wildtype mice treated with S1PR1-antagonists. Wildtype HEVs treated with S1PR1-antagonists in vitro and Lyve1-deficient HEVs show severely reduced release of the DC-chemoattractant CCL21 in vivo. Together, our results reveal that EC-derived S1P warrants HEV-integrity through autocrine control of S1PR1-Gi signaling, and facilitates concomitant HEV-DC interactions.Simmons S., Sasaki N., Umemoto E., et al. High-endothelial cell-derived s1p regulates dendritic cell localization and vascular integrity in the lymph node. eLife 8, e41239 (2019); https://doi.org/10.7554/eLife.41239

ホンガク ドウソウ カイイン ノ キンム ジョウキョウ : ジョセイ イシ シエン オ メザス ヨビテキ ケンキュウ トシテ

雇用の分野における男女の均等な機会及び待遇の確保のために,「男女雇用機会均等法」が成立し,妊娠や出産を理由として職場で不利益な取り扱いをすることは禁じられている1).さらに,「男女共同参画社会基本法」が施行され,2006 年には日本医師会に男女共同参画委員会が設立している2).しかし,我が国の女性医師の就労に影響を与える因子を検討した先行研究によると,性差による就労上の不利益を経験した女性医師が多く,就労格差を女性医師は強く認識しているという結論となっている3).このことは日本ばかりではなく,海外でも同様に報告されている4,5).特に,女性医師は男性医師に比較して,非常勤パートタイムで勤務することが多いと報告されている3,4).パートタイムで働く主たる理由は,出産と子育てである5).多くの女性医師が子育てを優先するために仕方なくパートタイム勤務を選択していることは事実である.また,母性を優先させる選択は職場での昇進・キャリアアップを閉ざすという結果につながる 3).しかし,一方で女性にとって出産や育児は非常に大切な母性の獲得であり,出産を経験した女性医師は医師を職業として選択したことにより満足していると報告されている6).これが女性医師にとってのワーク・ライフ・バランスのジレンマになっている.さらに,現在,医師を養成する大学医学部では,男女は平等に入学できるが,過酷な労働を強いられる大学病院では,女性医師は常勤勤務から離職せざるを得なくなるというアンバランスが生じている.本研究は,本学の女性医師支援のあり方を考える予備的研究として,本学同窓会会員の現況報告を検討し,さらに女性医師支援に関する先行文献を考察することを目的とした

Electric Conductivity,Na+ Content and Photosynthetic Activity in Leaves of Salt-Stressed Rice Plants,and Their Cultivaral Difference

The electric conductivity of a leaf (LEC) was determined with an insulation resistance tester, and discussed its relationship with Na[+] content in a leaf (LNC) and the photosynthetic activity in salt-stressed rice cultivars. The measurements were carried out using three cultivars of O. sativa and O. glaberrima grown at the middle vegative growth stage. The plants showed a clear response to the salt treatment wothin 24 hours after its application. Both LEC and LNC in these cultivars increased with an increase in NaCl concentration in culture solution from 0 to 0.1 μmol L[-1]. LEC had a close linear relationship with LNC in each cultivar. A negative relationship was found between LEC and gross photosynthetic rate(Pg). The stomatal concuctance (Gs) and mesophyll conduntance (Gm) decreased with an increase in LNC. A clear cultivaral dofference was recognized in responces to salt treatments. LEC was regarded as a useful indicator for the estimation or diagnosis of LNC and photosynthetic activity in salt-stressed rice cultivars

Lipid droplet accumulation and adipophilin expression in follicular thyroid carcinoma

Follicular neoplasms of the thyroid include follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA). However, the differences in cytological findings between FTC and FTA remain undetermined. Here, we aimed to evaluate the accumulation of lipid droplets (LDs) and the expression of adipophilin (perilipin 2/ADRP/ADFP), a known LD marker, in cultured FTC cells. We also immunohistochemically compared adipophilin expression in the FTC and FTA of resected human thyroid tissues. Cultured FTC (FTC-133 and RO82W-1) possessed increased populations of LDs compared to thyroid follicular epithelial (Nthy-ori 3-1) cells. In vitro treatment with phosphatidylinositol-3-kinase (PI3K)/Akt/ mammalian target of rapamycin (mTOR) signaling inhibitors (LY294002, MK2206, and rapamycin) in FTC-133 cells downregulated the PI3K/Akt/mTOR/sterol regulatory element-binding protein 1 (SREBP1) signaling pathway, resulting in a significant reduction in LD accumulation. SREBP1 is a master transcription factor that controls lipid metabolism. Fluorescence immunocytochemistry revealed adipophilin expression in the LDs of FTC-133 cells. Immunohistochemical analysis of surgically resected human thyroid tissues revealed significantly increased expression of adipophilin in FTC compared with FTA and adjacent non-tumorous thyroid epithelia. Taken together, LDs and adipophilin were abundant in cultured FTC; the evaluation of adipophilin expression can help distinguish FTC from FTA in surgical specimens. (c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

High-endothelial cell-derived s1p regulates dendritic cell localization and vascular integrity in the lymph node

Simmons S., Sasaki N., Umemoto E., et al. High-endothelial cell-derived s1p regulates dendritic cell localization and vascular integrity in the lymph node. eLife 8, e41239 (2019); https://doi.org/10.7554/eLife.41239.While the sphingosine-1-phosphate (S1P)/sphingosine-1-phosphate receptor-1 (S1PR1) axis is critically important for lymphocyte egress from lymphoid organs, S1PR1-activation also occurs in vascular endothelial cells (ECs), including those of the high-endothelial venules (HEVs) that mediate lymphocyte immigration into lymph nodes (LNs). To understand the functional significance of the S1P/S1PR1-Gi axis in HEVs, we generated Lyve1;Spns2Δ/Δ conditional knockout mice for the S1P-transporter Spinster-homologue-2 (SPNS2), as HEVs express LYVE1 during development. In these mice HEVs appeared apoptotic and were severely impaired in function, morphology and size; leading to markedly hypotrophic peripheral LNs. Dendritic cells (DCs) were unable to interact with HEVs, which was also observed in Cdh5CRE-ERT2;S1pr1Δ/Δ mice and wildtype mice treated with S1PR1-antagonists. Wildtype HEVs treated with S1PR1-antagonists in vitro and Lyve1-deficient HEVs show severely reduced release of the DC-chemoattractant CCL21 in vivo. Together, our results reveal that EC-derived S1P warrants HEV-integrity through autocrine control of S1PR1-Gi signaling, and facilitates concomitant HEV-DC interactions