p38 Mitogen-activated Protein Kinase Regulates Oscillation of Chick Pineal Circadian Clock

Extracellular signal-regulated kinase (ERK) and p38 are members of the mitogen-activated protein kinase (MAPK) family, and in some cases these kinases serve for closely related cellular functions within a cell. In a wide range of animal clock structures, ERK plays an important role in the circadian time-keeping mechanism. Here we found that immunoreactivity to p38 protein was uniformly distributed among cells in the chick pineal gland. On the other hand, a constant level of activated p38 was detected over the day, predominantly in the follicular and parafollicular pinealocytes that are potential circadian clock-containing cells. Chronic application of SB203580, a selective and reversible inhibitor of p38, to the cultured chick pineal cells markedly lengthened the period of the circadian rhythm of the melatonin release (up to 28.7 h). Noticeably, despite no significant temporal change of activated p38 level, a 4-h pulse treatment with SB203580 delayed the phase of the rhythm only when delivered during the subjective day. These results indicate a time-of-day-specific role of continuously activated p38 in the period length regulation of the chick pineal clock and suggest temporally separated regulation of the clock by two MAPKs, nighttime-activated ERK and daytime-working p38

音象徴に基づくオノマトペの印象評価システムと生成システムの設計

日本語には，現実の具体的な音声や，様子，心情などを音で表現する語であるオノマトペ（擬音語・擬態語の総称）が豊富に存在する．オノマトペは多様な概念を感覚的かつ直接的に表現することができ，生き生きとした臨場感のある描写を実現する上で，不可欠な言語要素である．また，オノマトペには新しい語形を次々と作り出す力が備わっており，より創作的・独創的なオノマトペ表現のほうが，聞き手・読み手にとってイメージがより具体的に喚起されるため，効果的であるともされる．一方で，オノマトペは本人の感覚経験と強く結びついているために，あいまいで主観的な表現でもあり，客観的にその印象を扱うことは難しい．多様な感覚を表し，新奇性のある表現が作られうるオノマトペの感性的な印象を，客観的に評価する手法を確立することには大きな意義があると考えられる．ゆえに，そのようなオノマトペの創作および活用を有効に支援することができれば，社会および文化の発展に大きく貢献できるものと考えられる．したがって本論文では，オノマトペの創作活動を支援するために，主観的なオノマトペごとの微妙な印象や，相互に似通ったオノマトペの差異を客観的に評価する「オノマトペの印象評価システム」と，広告やネーミング，漫画などの制作の現場において，制作者の所望する印象を与えるオノマトペを探索する「オノマトペの生成システム」の2 つのシステムを設計・開発することを目的とした．言語学においては一般に，言語の音とその語によって表される意味の間の関係は必然的なものでなく，恣意的なものであるとされてきた．しかしオノマトペにおいては，言語の音韻と意味との間に何らかの合理的・感覚的な結びつきが見られる場合があり，このような現象を音象徴という．すなわち，オノマトペのもつ基本的な音象徴的意味を，その語の構成する音から予測することができるとされる．近年，言語学分野や心理学分野において，音象徴に着目した従来研究があり，オノマトペにおける体系的な音象徴性が論じられてきた．一方で，オノマトペが感覚に直接結びつく特性に着目した工学的研究が近年多く存在する．しかしこれらの工学的研究のうち，オノマトペに内在する感性的な印象を，音象徴性に基づいて直接的かつ客観的に扱っている研究事例は少ないのが現状であった．そこで，本論文においては，心理学的手法によって音と意味の間の対応関係を調査し，オノマトペを構成する個々の音韻から印象を予測する手法を考えた．そして，この音象徴に基づく印象予測モデルを用いて，オノマトペの印象評価システムとオノマトペの生成システムを設計・開発した．本論文は全5 章から構成され，各章の概要は以下の通りである．第1 章では，研究の社会的背景として，オノマトペの社会における利活用の事例を取り上げ，オノマトペのもつ創作的な特徴と，創作活動における課題について述べる，本論文の目的として，感性的な印象を客観的に扱う手法を確立し，オノマトペの創作支援を可能にするシステムを設計・開発することと定める．第2 章では，まずオノマトペの分類と定義について述べる．擬音語や擬態語など多様な概念を含むオノマトペの分類についての概要を示し，本論文で扱うオノマトペの範囲を定義する．次に，オノマトペに関連する文理両分野における従来研究を取り上げる．オノマトペの特徴である音象徴性について概説し，20 世紀の欧米言語学と欧米心理学，日本語学における研究の流れに加え，オノマトペの感性的側面を工学分野に取り入れた近年の研究についても概観する．ここで，オノマトペの音象徴に基づいたシステムの設計・開発の背景となる知見を共有し，本論文の意義と位置づけを明確にする．第3 章では，オノマトペの印象評価システムの設計・開発に関する研究について述べる．あいまいとされるオノマトペの意味を客観的に推定するために，オノマトペの特徴である音象徴性に着目する．オノマトペを構成する個々の音韻の要素からオノマトペ全体の印象を予測するモデルを構築し，辞書データベースに頼らない印象評価手法を試みることによって，新しく創出された新奇性のある表現についても，客観的な印象評価を可能にする．第4 章では，オノマトペの生成システムの設計・開発に関する研究について述べる．第3 章で述べたオノマトペの印象評価手法を応用し，ユーザがシステム上で任意に入力した印象評価値を目的として，遺伝的アルゴリズムによるオノマトペの探索・最適化手法を実現することによって，ユーザの直感的な印象に合致したオノマトペを生成する手法を試みる．また，生成システムと印象評価システムとを統合し連携させることによって，ユーザの印象により適合したオノマトペを探索する活用法を可能にする．第5 章では，本論文の総括として，オノマトペの印象評価システムおよびオノマトペの生成システムの設計・開発に関する研究を振り返り，明らかになった課題について議論する．そして，両システムの活用や新たなシステムの設計，オノマトペの工学的応用に関する今後の展望についても論じる．電気通信大学201

Effect of Suplatast Tosilate on Antileukotriene Non-Responders with Mild-to-Moderate Persistent Asthma

ABSTRACTBackgroundImmunomodulatory therapy has been recently introduced for the management of asthma. Suplatast tosilate (ST), a new immune-modifying drug, is known to improve the airway function by inhibiting the release of Th-2 cytokines. However, its efficacy as a controller listed in the guideline, Global Initiative for Asthma 2005 has not been established. In this study we investigated the role of ST in leukotriene receptor antagonist (LTRA) non-responders with mild-to-moderate persistent asthma before initiating corticosteroids inhalation therapy.MethodsThis was a prospective open-level clinical trial. LTRAs was given to 41 patients with asthma for 4 weeks and clinical efficacy was assessed using daily symptom scores. The 10 patients, aged 2.5-8.5 years, who failed to show clinical improvement, were defined as LTRA non-responders. After a 1-week washout period, the efficacy of ST was investigated and compared with LTRA non-responders for the following 4 weeks.ResultsLTRA non-responders showed a significant improvement in the average symptom score, peak expiratory flow, use of rescue medication and the proportion of symptom-free days with ST therapy.ConclusionsST is a good choice for patients who have failed to respond to LTRAs. ST should therefore be added to the list of treatment options for such patients

Preparation of Cu-doped TiO2 via refluxing of alkoxide solution and its photocatalytic properties

Cu-doped TiO2 was prepared by the refluxing of a mixture of copper and titanium alkoxides. The refluxing improved the Cu2+ dispersion in the TiO2 and formed effective Ti-O-Cu bonds. The impurity states due to the highly dispersed Cu2+ were presumed to trap the electrons in the conduction band of the TiO2 and prevent charge recombination of the electrons and holes. Consequently, the prolonged charge separation duration was suggested to enhance the photocatalytic activity of the Cu-doped TiO2. This enhancement was confirmed by the hydroxyl radical generation and organic compound degradation. The Ti-O-Cu bonds and electronic interaction between Cu and Ti should effectively promote the electron trapping. The Cu-doped TiO2 exhibited a visible light-induced activity due to the transition from the TiO2 valence band to the Cu2+ impurity states.ArticleRESEARCH ON CHEMICAL INTERMEDIATES. 38(2):595-613 (2012)journal articl

Hypertrophy and Unconventional Cell Division of Hepatocytes Underlie Liver Regeneration

SummaryBackgroundThe size of organs and tissues is basically determined by the number and size of their cells. However, little attention has been paid to this fundamental concept. The liver has a remarkable ability to regenerate after surgical resection (partial hepatectomy [PHx]), and hepatocytes account for about 80% of liver weight, so we investigate how the number and size of hepatocytes contribute to liver regeneration in mice. It has been generally accepted that hepatocytes undergo one or two rounds of cell division after 70% PHx. However, ploidy of hepatocytes is known to increase during regeneration, suggesting an unconventional cell cycle. We therefore examine cell cycle of hepatocytes in detail.ResultsBy developing a method for genetic fate mapping and a high-throughput imaging system of individual hepatocytes, we show that cellular hypertrophy makes the first contribution to liver regeneration; i.e., regeneration after 30% PHx is achieved solely by hypertrophy without cell division, and hypertrophy precedes proliferation after 70% PHx. Proliferation and hypertrophy almost equally contribute to regeneration after 70% PHx. Furthermore, although most hepatocytes enter cell cycle after 70% PHx, not all hepatocytes undergo cell division. In addition, binuclear hepatocytes undergo reductive divisions to generate two mononuclear daughter hepatocytes in some cases.ConclusionsOur findings demonstrate the importance of hypertrophy and the unconventional cell division cycle of hepatocytes in regeneration, prompting a significant revision of the generally accepted model of liver regeneration

Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions

We showed that XPC complex, which is a DNA damage detector for nucleotide excision repair, stimulates activity of thymine DNA glycosylase (TDG) that initiates base excision repair. XPC appeared to facilitate the enzymatic turnover of TDG by promoting displacement from its own product abasic site, although the precise mechanism underlying this stimulation has not been clarified. Here we show that XPC has only marginal effects on the activity of E. coli TDG homolog (EcMUG), which remains bound to the abasic site like human TDG but does not significantly interacts with XPC. On the contrary, XPC significantly stimulates the activities of sumoylated TDG and SMUG1, both of which exhibit quite different enzymatic kinetics from unmodified TDG but interact with XPC. These results point to importance of physical interactions for stimulation of DNA glycosylases by XPC and have implications in the molecular mechanisms underlying mutagenesis and carcinogenesis in XP-C patients

Induction of macrophage migration inhibitory factor precedes the onset of acute tonsillitis.

We investigated the serum macrophage migration inhibitory factor (MIF) levels of palmoplantar pustulosis patients, before and after the tonsillar provocation test. Higher serum MIF levels of palmoplantar pustulosis patients were decreased after the tonsillar provocation test (n=29). To confirm these phenomena, two patients with acute tonsillitis had their changes in body temperature, C-reactive protein (CRP) and serum MIF levels examined during the course of their illness. Surprisingly, increased MIF preceded fever and CRP elevation, and MIF subsequently decreased at the onset of fever and CRP elevation. Since MIF is an initiator of other proinflammatory cytokines, we suggest that the induction of MIF may precede other inflammatory conditions