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【目的】代謝状態の朝晩の変化を理解することは、代謝障害を管理するためには重要である。我々は、インスリン分泌とインスリン感受性の観点からこの朝晩の変化を解析し、さらに概日リズムとの関連性を含めて検討することを目的とした。 【方法】非糖尿病成人男性14人と10人に対し、それぞれ75ｇ経口ブドウ糖負荷試験(OGTT)と高インスリン正常血糖（HE）クランプ実験を行った。各被験者に対し、午前8時と午後8時にOGTTまたはHEクランプを1回ずつ行った。ただし試験時間の順序は無作為とした。各試験直前に毛根を採取し、毛包における時計遺伝子発現量をリアルタイムPCR法で解析した。また、マウスの肝臓と筋肉でもAKTリン酸化をウエスタンブロット法により解析した。 【結果】OGTTの結果から、耐糖能は午前8時の方が良好であることがわかった。これは、OGTTにおける負荷後60分までのインスリン早期分泌とHEクランプで説明される骨格筋インスリン感受性の違いに起因すると考えられた。一方、OGTTにおける肝臓のインスリン抵抗性指数によって推定される肝インスリン感受性は、午後8時の方が良好であった。60分までのインスリン分泌量と肝臓のインスリン抵抗性指数の朝晩の差は、Per2のｍRNAの相対的発現量と有意に相関していた。ΔGIR（20時の値－8時の値）は、Δ非エステル化脂肪酸（NEFA）と有意に相関したが、時計遺伝子発現との相関は認められなかった。ΔNEFAは、E4bp4のmRNA発現量およびΔコルチゾールと有意に相関していた。マウスでは、ヒトの研究から予想されるように、AKTリン酸化は活動時間の初めに肝臓で減少し、筋肉で増加していた。 【結語】各組織の糖代謝は朝と晩で大きく異なっており、脂質代謝、時計遺伝子およびコルチゾールの影響を受けていることがわかった。この関連性についてのより深い知見が代謝障害の新たな改善法の開発に寄与する可能性がある。

右心室 (RV) の機能障害とそれに関連する不整脈は、肺動脈性肺高血圧症 (PAH) の予後の重要な決定要因として認識されている。今回心臓リアノジン受容体 (RyR2) の安定剤であるダントロレン (DAN) による右室心筋への直接的な薬理学的介入が、モノクロタリン (MCT) 誘発性PAHラットモデルにおいてRV機能障害および不整脈に対する保護効果を有するかどうかを調査することを目的とした。方法として雄の8週齢のSprague-Dawleyラットに、PAHの誘発のためにMCTを腹腔内投与した。カテコールアミンによる心室頻拍 (VT) の誘発も、単離された心筋細胞におけるRyR2を介したCa^{2+}放出特性に関連して評価された。RVの形態と機能に対する慢性的な圧力過負荷の独立した影響を評価するためには、肺動脈縮窄モデルも確立した。結果、MCT誘発PHAラットモデルでは、RV肥大、拡張、および機能低下が観察され、MCT誘発2か月後の生存率は0%であった。対照的に、慢性DAN治療はこれらすべてのRVパラメータを改善し、生存率を80%に増加させた。慢性的なDAN療法はまた、RyR2からのカルモジュリンの解離を防ぎ、それによってMCTによって誘発された肥大したRV心筋細胞におけるCa^{2+}スパークと自発的なCa^{2+}トランジェストを抑制した。エピネフリンは、MCT誘発性PAHのラットの50%以上でVTを誘発したが、慢性DAN治療によってVTの完全に抑制した。以上よりDANによるRyR2の安定化は、PAHに関連するRV機能障害および致命的な不整脈の発症に対する新しい治療薬としての可能性を秘めている。

We previously discovered that SPC/Fyn/Rho-kinase (ROK) pathway mediates the Ca^{2+}-sensitization of coronary arterial smooth muscle (CASM) contraction leading to vasospasm, a major cause of sudden death. Lately, we have been trying to find and develop more natural edible compounds which can treat and/or prevent the SPC-induced abnormal CASM contraction, and finally the first to discover that tangeretin (5,6,7,8,4'-prentamethoxyflavone), a natural compound extracted from citrus plants, can inhibit the SPC-induced CASM contraction both in the pretreatment and posttreatment. In porcine CASM tissues, tangeretin showed remarkable inhibitory effects on the SPC-induced contraction with modest inhibitory effects on the high K^+-depolarization-induced Ca^{2+}-dependent contraction, both in pretreatment and posttreatment at the optimal concentrations; Regarding the mechanisms, tangeretin markedly abolished the SPC-induced cell contraction through inhibiting the SPC-induced activation and translocation of Fyn and ROK from the cytoplasm to the cell membrane in cultured CASM cells, resulting in the reduction of phosphorylation of myosin light chain. Taken together, these findings indicate that tangeretin, upon pre- or post- treatment, inhibits the SPC-induced CASM contraction through suppressing the Fyn/ROK signaling pathway, thereby suggesting that tangeretin can be a potential candidate for the treatment and/or prevention of vasospasm.

Huntingtin-associated protein 1 (HAP1) is a neural huntingtin interactor and being considered as a core molecule of stigmoid body (STB). Brain or spinal cord regions with abundant STB/HAP1 expression are usually spared from neurodegeneration, whereas the regions with little STB/HAP1 expression are always neurodegenerative targets. The enteric nervous system (ENS) can act as a potential portal for pathogenesis of neurodegenerative disorders. To date, the expression of HAP1 and its neurochemical characterization have never been examined there. In the current study, we determined the expression and immunohistochemical phenotypes of HAP1 in ENS of adult rodents using Western blotting and light/fluorescence microscopy. HAP1 immunoreactivity was strongly expressed in both myenteric and submucosal plexuses of ENS. STBs were observed in the cytoplasm of most of the HAP1-immunoractive (ir) cells in ENS. In myenteric plexus, a large number of calretinin, calbindin, NOS, VIP, ChAT, SP, somatostatin, and TH-ir neurons showed HAP1 immunoreactivity. In contrast, most of the CGRP-ir neurons were devoid of HAP1-immunoreactivity. In submucosal plexus, almost all the cholinergic secretomotor neurons containing ChAT/ CGRP/ somatostatin/ calretinin, non-cholinergic secretomotor neurons containing VIP/TH/calretinin and vasodilator neurons containing VIP/calretinin express HAP1. Our current study is the first to clarify that HAP1 is highly expressed in excitatory motor neurons, inhibitory motor neurons, and interneurons but almost absent in sensory neurons in myenteric plexus. While, HAP1 is expressed in all neuronal subgroups of Meissner’s plexuses. These suggest that due to lack of putative STB/HAP1 protectivity, the sensory neurons (Dogiel type II) might be more vulnerable to neurodegeneration than STB/HAP1-expressing Dogiel type I neurons in myenteric plexus and secretomotor/vasodilator in Meissner’s plexuses. Our current results may reflect the involvement of HAP1 in modulation of excitatory and inhibitory motor neuron functions in myenteric plexus and the secretomotor and vasodilator functions of submucosal neurons. It will be of great interest to elucidate the physiological or pathological roles of HAP1 in ENS. Our current results might lay a basic foundation for future studies that seek to clarify the physiological/pathological effects of STB/HAP1 in the ENS.

Zero-determinant strategies are memory-one strategies in repeated　games which unilaterally enforce linear relations between expected payoffs of　players. Recently, the concept of zero-determinant strategies was extended　to　the class of memory-n strategies with n _ 1, which enables more compli-cated control of payoffs by one player. However, what we can do by　memory-n　zero-determinant strategies is still not clear. Here, we show that memory-n　zero-determinant strategies in repeated games can be used to control condi-tional expectations of payoffs. Equivalently, they can be used to control ex-pected payoffs in biased ensembles, where a history of action pro_les with large　value of bias function is more weighted. Controlling conditional expectations　of payoffs is useful for strengthening zero-determinant strategies, because play-ers can choose conditions in such a way that only unfavorable action pro_les　to one player are contained in the conditions. We provide several examples　of memory-n zero-determinant strategies in the repeated prisoner's dilemma　game. We also explain that a deformed version of zero-determinant strategies　is easily extended to the memory-n case.

To date, the process of implementing the global Sustainable Development Goals （SDGs） and global climate change mitigation and adaptation obligations has been largely decoupling in most countries. This creates administrative duplication, costs, and hinders the development of effective problem solving. Against this background, we show the present state of research on policy integration and integrated policymaking. Following the research results of Bauer et al. （2021） and Teebken et al. （2021）, this note briefly summarizes different understandings of policy integration and detailed criteria for evaluating policy integration from different　academic perspectives. Implementing an interactive agenda requires political　attention and institutional competence to address the interactions and complexity　of each, understand policies at a national level, and translation. In this note, we will　introduce the basic concept of what integration practice looks like, and focusing on　the interaction between the 2030 Agenda and the Paris Agreement.

The purpose of this paper is to analyze the movement of the economy when the consumption demand is fully realized after the economy achieves full employment. If the investment demand is fully realized, full employment will not be sustained. However, full employment will continue if the consumption demand is fully realized.

本稿では，中国の浙江省の消費者を対象に実施したアンケート調査をもとに，新型コロナウイルス感染症の拡大が中国の消費者の消費行動に与えた影響を探るために，OLS回帰分析を用いて定量分析を行った。分析結果から，新型コロナウイルス感染症の拡大は中国における消費者の収入や仕事の安定さに一定の影響を与えていることがわかった。多くの回答者は将来の経済発展に対し強い確信を持っていることも確認された。また，新型コロナウイルス感染症の影響が強ければ強いほど節約的消費傾向が強まり，将来に確信を持つほど積極的消費傾向が強まることがわかった。

This paper empirically examines the impacts of household debt and　leverage ratio, measured by the ratio of aggregate household debt to GDP, on consumption using provincial-level macro-data in China. Results show that household indebtedness has a positive and significant effect on consumption expenditure and this remains true for both household debt and leverage ratio, as well as long-term and short-term debts and leverage ratios, and the encouraging effects are heterogeneous across regions. When the debt-to-GDP ratio is below 100%, the consumption experiences faster growth than that when the debt-to-GDP ratio exceeds 100%. In addition, residents’ saving, per capita disposal income and the public expenditure on education, social security, as well as medical and health services are found to have significant positive effects on consumption, while CPI and child dependency ratio have depressive effects.

As income levels increase, numerous households will consider investing in risky assets. Credit availability, especially for high-income households, is playing an increasingly important role in enhancing households holdings of risky assets (HHRA). The purpose of this study is to investigate the impact of credit availability on HHRA. In this study, the data from the China Household Finance Survey in 2017 is utilized, and the approach of logit regression is employed to produce more accurate estimates. Meanwhile, this study also explores the heterogeneous roles of household income. The results show that the impact of credit availability on HHRA varies by household income. As household income increases from low to high, the effect of credit availability on HHRA transfers from negative to positive. Besides, the results also suggest that for high-income households, credit availability moderated with the attention to financial and economic information positively contributes to HHRA. Thus, it implies that policymakers and financial institutions are encouraged to expand access for households to invest in risky assets, enhance households’ availability of credit, and build more financing channels.