Soft Crystals: Science and Photofunctions of Easy-Responsive Systems with Felxibility and Higher-Ordering

金沢大学理工研究域物質化学系蒸気などの弱いマクロ刺激で相転移を生じるソフトクリスタルの創製において、元々穴の空いた剛直な環状分子を弱い相互作用により連結した多孔性結晶の作成は有用なストラテジーとなり得る。本研究では、自由回転ができない堅い骨格を有するベルト状自己集合型金属錯体「メタロナノベルト」を合成し、これを様々な非共有結合性の相互作用で連結することで、蒸気などの外部刺激に対して応答しやすい内在性細孔を持つソフトクリスタルを創製することを目的として研究を行った。令和元年度は、平成３０年度に構築したメタロナノベルトをソフトクリスタルのビルディグブロックに用いるために、自在官能基化の手法を確立した。トリプチセンから二段階で合成可能なヘキサアミノトリプチセンを共通の前駆体とし、多様な1,2-ジケトン類と反応させることで、キノキサリン骨格形成を鍵反応とし、様々な官能基を有する屈曲型配位子を合成した。さらにこれら配位子を用いて官能基化されたメタロナノベルトを効率的に形成した。特に、金属配位部位であるピリジル基やメタロナノベルト骨格と多点水素結合を形成するトリエチレングリコール鎖などの相互作用部位を導入したメタロナノベルトの構築に成功した。今後これらの相互作用部位を足場としてソフトクリスタルを戦略的に創製できると期待される。さらに、回転運動や並進運動などの動的特性を有するロタキサンを結晶内に組み込むことによっても新たなソフトクリスタルの創製にも挑んだ。ビオロゲン誘導体を軸分子、クラウンエーテル誘導体を輪分子として様々な組み合わせを試みた結果、ジフェニルビオロゲンとDB24C8との組み合わせにおいて[3]擬ロタキサンが協同的に形成することを発見した。その相互作用の詳細について明らかにするために、現在検討を行っている。研究課題/領域番号:18H04511, 研究期間(年度):2018-04-01 – 2020-03-31出典：研究課題「内在性細孔を持つイオン性結晶を用いた格子欠陥誘起型ソフトクリスタルの創製」課題番号18H04511（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-PUBLICLY-18H04511/）を加工して作

Changes in work and life patterns associated with depressive symptoms during the COVID-19 pandemic: an observational study of health app (CALO mama) users

BACKGROUND: During the COVID-19 pandemic, many people refrained from going out, started working from home (WFH), and suspended work or lost their jobs. This study examines how such pandemic-related changes in work and life patterns were associated with depressive symptoms. METHODS: An online survey among participants who use a health app called CALO mama was conducted from 30 April to 8 May 2020 in Japan. Participants consisted of 2846 users (1150 men (mean age=50.3) and 1696 women (mean age=43.0)) who were working prior to the government declaration of a state of emergency (7 April 2020). Their daily steps from 1 January to 13 May 2020 recorded by an accelerometer in their mobile devices were linked to their responses. Depressive symptoms were assessed using the Two-Question Screen. RESULTS: On average, participants took 1143.8 (95% CI -1557.3 to -730.2) fewer weekday steps during the declaration period (from 7 April to 13 May). Depressive symptoms were positively associated with female gender (OR=1.58, 95% CI 1.34 to 1.87), decreased weekday steps (OR=1.22, 95% CI 1.03 to 1.45) and increased working hours (OR=1.73, 95% CI 1.32 to 2.26). Conversely, starting WFH was negatively associated with depressive symptoms (OR=0.83, 95% CI 0.69 to 0.99). CONCLUSIONS: Decreased weekday steps during the declaration period were associated with increased odds of depressive symptoms, but WFH may mitigate the risk in the short term. Further studies on the longitudinal effects of WFH on health are needed

コンバラトキシンによる凝固亢進における単球由来組織因子陽性細胞外小胞の関与

Objectives: Convallatoxin (CNT) is a natural cardiac glycoside extracted from lily of the valley (Convallaria majalis). Although it is empirically known to cause blood coagulation disorders, the underlying mechanism remains unclear. CNT exerts cytotoxicity and increases tissue factor (TF) expression in endothelial cells. However, the direct action of CNT on blood coagulation remains unclear. Therefore, herein, we investigated the effects of CNT on whole blood coagulation system and TF expression in monocytes. Methods: Blood samples were collected from healthy volunteers to measure plasma thrombin–antithrombin complex (TAT) concentration using ELISA and to perform rotational thromboelastometry (ROTEM) and whole-blood extracellular vesicle (EV)-associated TF (EV-TF) analysis. The effects of CNT were also investigated using the monocytic human cell line THP-1. Quantitative real-time PCR and western blotting were performed, and PD98059, a mitogen-activated protein kinase (MAPK) inhibitor, was used to elucidate the action mechanism of CNT-mediated TF production. Results: CNT treatment increased EV-TF activity, shortened the whole blood clotting time in rotational thromboelastometry analysis, and increased TAT levels, which is an index of thrombin generation. Furthermore, CNT increased TF mRNA expression in THP-1 cells and EV-TF activity in the cell culture supernatant. Therefore, CNT may induce a hypercoagulable state with thrombin generation, in which elevated EV-TF activity derived from monocytes might be involved. These procoagulant effects of CNT were reversed by PD98059, suggesting that CNT-induced TF production in monocytes might be mediated by the MAPK pathway. Conclusions: The findings of the present study have further clarified the procoagulant properties of CNT.本文は発行元が定める公開猶予期間終了後に公開

Development of Benevolent Sexism Scale for working women in Japan

Even though many women continue to work after marriage or childbirth nowadays, the number of women in managerial positions is still lower in Japan than in other countries. Benevolent sexism (BS) at the workplace has been considered one of the obstacles that prevent women from being promoted. Based on ambivalent sexism theory (Glick & Fiske, 1996), we developed a new scale to measure BS toward working women in order to investigate how BS affects womenʼs promotion in Japan. After performing a series of factor analyses and examining the validity using an original BS scale and other related scales, eight items were found to adequately construct three theoretical factors of BS.本研究は広島大学大学院教育学研究科倫理審査委員会の承認を受けて行われた（承認番号2019595）。本研究の一部は日本心理学会第第82回大会で発表した。また，本研究は科研費18K03007の助成を受けた

Adult Thymic Medullary Epithelium Is Maintained and Regenerated by Lineage-Restricted Cells Rather Than Bipotent Progenitors

Medullary thymic epithelial cells (mTECs) play an essential role in establishing self-tolerance in T cells. mTECs originate from bipotent TEC progenitors that generate both mTECs and cortical TECs (cTECs), although mTEC-restricted progenitors also have been reported. Here, we report in vivo fate-mapping analysis of cells that transcribe β5t, a cTEC trait expressed in bipotent progenitors, during a given period in mice. We show that, in adult mice, most mTECs are derived from progenitors that transcribe β5t during embryogenesis and the neonatal period up to 1 week of age. The contribution of adult β5t+ progenitors was minor even during injury-triggered regeneration. Our results further demonstrate that adult mTEC-restricted progenitors are derived from perinatal β5t+ progenitors. These results indicate that the adult thymic medullary epithelium is maintained and regenerated by mTEC-lineage cells that pass beyond the bipotent stage during early ontogeny

State- and water repellency-controllable molecular glass of pillar[5]arenes with fluoroalkyl groups by guest vapors

Molecular glasses are low-molecular-weight organic compounds that are stable in the amorphous state at room temperature. Herein, we report a state- and water repellency-controllable molecular glass by n-alkane guest vapors. We observed that a macrocyclic host compound pillar[5]arene with the C₂F₅ fluoroalkyl groups changes from the crystalline to the amorphous state (molecular glass) by heating above its melting point and then cooling to room temperature. The pillar[5]arene molecular glass shows reversible transitions between amorphous and crystalline states by uptake and release of the n-alkane guest vapors, respectively. Furthermore, the n-alkane guest vapor-induced reversible changes in the water contact angle were also observed: water contact angles increased and then reverted back to the original state by the uptake and release of the n-alkane guest vapors, respectively, along with the changes in the chemical structure and roughness on the surface of the molecular glass. The water repellency of the molecular glass could be controlled by tuning the uptake ratio of the n-alkane guest vapor

Dissociation of Tau Deposits and Brain Atrophy in Early Alzheimer’s Disease: A Combined Positron Emission Tomography/Magnetic Resonance Imaging Study

The recent advent of tau-specific positron emission tomography (PET) has enabled in vivo assessment of tau pathology in Alzheimer’s disease (AD). However, because PET scanners have limited spatial resolution, the measured signals of small brain structures or atrophied areas are underestimated by partial volume effects (PVEs). The aim of this study was to determine whether partial volume correction (PVC) improves the precision of measures of tau deposits in early AD. We investigated tau deposits in 18 patients with amyloid-positive early AD and in 36 amyloid-negative healthy controls using 18F-THK5351 PET. For PVC, we applied the SPM toolbox PETPVE12. The PET images were then spatially normalized and subjected to voxel-based group analysis using SPM12 for comparison between the early AD patients and healthy controls. We also compared these two groups in terms of brain atrophy using voxel-based morphometry of MRI. We found widespread neocortical tracer retention predominantly in the posterior cingulate and precuneus areas, but also in the inferior temporal lobes, inferior parietal lobes, frontal lobes, and occipital lobes in the AD patients compared with the controls. The pattern of tracer retention was similar between before and after PVC, suggesting that PVC had little effect on the precision of tau load measures. Gray matter atrophy was detected in the medial/lateral temporal lobes and basal frontal lobes in the AD patients. Interestingly, only a few associations were found between atrophy and tau deposits, even after PVC. In conclusion, PVC did not significantly affect 18F-THK5351 PET measures of tau deposits. This discrepancy between tau deposits and atrophy suggests that tau load precedes atrophy

A diagnostic marker for superficial urothelial bladder carcinoma : lack of nuclear ATBF1 (ZFHX3) by immunohistochemistry suggests malignant progression

Background: Pathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection (TUR). AT-motif binding factor 1 (ATBF1) is a tumor suppressive transcription factor that is normally localized to the nucleus but has been detected in the cytoplasm in several cancers. Here, we examined the diagnostic value of the intracellular localization of ATBF1 as a marker for the identification of high risk urothelial bladder carcinoma. Methods: Seven anti-ATBF1 antibodies were generated to cover the entire ATBF1 sequence. Four human influenza hemagglutinin-derived amino acid sequence-tagged expression vectors with truncated ATBF1 cDNA were constructed to map the functional domains of nuclear localization signals (NLSs) with the consensus sequence KR[X10-12]K. A total of 117 samples from initial TUR of human bladder carcinomas were analyzed. None of the patients had received chemotherapy or radiotherapy before pathological evaluation. Results: ATBF1 nuclear localization was regulated synergistically by three NLSs on ATBF1. The cytoplasmic fragments of ATBF1 lacked NLSs. Patients were divided into two groups according to positive nuclear staining of ATBF1, and significant differences in overall survival (P = 0.021) and intravesical recurrence-free survival (P = 0.013) were detected between ATBF1+ (n= 110) and ATBF1− (n=7) cases. Multivariate analysis revealed that ATBF1 staining was an independent prognostic factor for intravesical recurrence-free survival after adjusting for cellular grading and pathological staging (P = 0.008). Conclusions: Cleavage of ATBF1 leads to the cytoplasmic localization of ATBF1 fragments and downregulates nuclear ATBF1. Alterations in the subcellular localization of ATBF1 due to fragmentation of the protein are related to the malignant character of urothelial carcinoma. Pathological evaluation using anti-ATBF1 antibodies enabled the identification of highly malignant cases that had been overlooked at initial TUR. Nuclear localization of ATBF1 indicates better prognosis of urothelial carcinoma