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Vascular endothelium is known to play its various physiological roles in response to mechanical stress. In this study, the effects of mechanical stress especially hypotonic stress on endothelial responses have been examined, and the modification of these responses by gravity overload has been examined. Endothelial cells from bovine aorta (BAEC) were used, and the intracellular Ca(2+) concentration ((Ca(2+))(sub i)), membrane current and extracellular ATP concentration were measured. Mechanical stress was applied to BAEC by perfusing hypotonic solution or low speed centrifugation. Hypotonic stress activated tyrosine kinase, small G-protein Rho and Rho kinase, thereby releasing ATP out of the cell. The released ATP elicited Ca(2+) oscillations and the following nitric oxide production in BAEC, thus indicating that this system plays a significant role in endothelial homeostasis. Furthermore, ATP release was augmented by gravity overload, so it was concluded that the mechanosensitive ATP release is one of the gravity-sensitive systems in vascular endothelium., 目的:血管内皮は機械的刺激を感知してその機能を果たしていることが知られている。本研究では、血管内皮細胞の機械的刺激特に低浸透圧刺激に対する反応とそれに及ぼす重力負荷の影響を検討した。方法:実験にはウシ大動脈の内皮を用い、細胞内Ca(2+)濃度測定、膜電流測定、細胞外ATP濃度測定などを行い、機械的刺激は低浸透圧液潅流および低速遠心機による重力負荷によって加えた。結果:低浸透圧刺激を加えると、チロシンキナーゼと小分子G蛋白Rhoの活性化、さらにRho-キナーゼの活性化によって細胞外にATPが放出された。このATPによって内皮自身にCa(2+)オシレーションが生じ、さらに一酸化窒素の産生が引き起こされたことから、この系は血管のホメオスターシス維持に重要な役割を果たしていると考えられた。またこのATPの放出は重力負荷によって促進され、この一連の反応が重力感知機構の一部として存在している可能性が考えられた。, NASDA Special Publication, 宇宙開発事業団特別報告

The molecular mechanism underlying Ca2+/calmodulin (CaM)-dependent kinase II (CaMKII)-mediated regulation of the mouse transient receptor potential channel TRPC6 was explored by chimera, deletion and site-directed mutagenesis approaches. Induction of currents (ICCh) in TRPC6-expressing HEK293 cells by a muscarinic agonist carbachol (CCh; 100 μm) was strongly attenuated by a CaMKII-specific peptide, autocamtide-2-related inhibitory peptide (AIP; 10 μm). TRPC6/C7 chimera experiments showed that the TRPC6 C-terminal sequence is indispensable for ICCh to be sensitive to AIP-induced CaMKII inhibition. Further, deletion of a distal region (Gln855–Glu877) of the C-terminal CaM/inositol-1,4,5-trisphosphate receptor binding domain (CIRB) of TRPC6 was sufficient to abolish ICCh. Systematic alanine scanning for potential CaMKII phosphorylation sites revealed that Thr487 was solely responsible for the activation of the TRPC6 channel by receptor stimulation. The abrogating effect of the alanine mutation of Thr487 (T487A) was reproduced with other non-polar amino acids, namely glutamine or asparagine, while being partially rescued by phosphomimetic mutations with glutamate or aspartate. The cellular expression and distribution of TRPC6 channels did not significantly change with these mutations. Electrophysiological and immunocytochemical data with the Myc-tagged TRPC6 channel indicated that Thr487 is most likely located at the intracellular side of the cell membrane. Overexpression of T487A caused significant reduction of endogenous TRPC6-like current induced by Arg8-vasopressin in A7r5 aortic myocytes. Based on these results, we propose that the optimal spatial arrangement of a C-terminal domain (presumably the distal CIRB region) around a single CaMKII phosphorylation site Thr487 may be essential for CaMKII-mediated regulation of TRPC6 channels. This mechanism may be of physiological significance in a native environment such as in vascular smooth muscle cells.

Chapter One: Literary Translation Studies, Japanese-to-English Translation, and Izu no odoriko This introductory chapter explores aspects of Translation Studies relevant to Japanese-to-English literary translation. I employ extended metaphors from the case study, Kawabata Yasunari's novella Izu no odoriko,to re-illuminate perennial TS issues such as equivalence, 'style' and disambiguation, contrasting the translating approaches of Edward G. Seidensticker and J. Martin Holman. The chapter concludes with an outline of the investigative path I followed in analysing the sourcetext (ST) and comparing it with the target texts (TTs): the English translations. I explain the thesis's systematic corpus approach in using an NVivo database to establish a set of potentially problematic translation issues that arise out of the interaction of source language-target language (SL-TL) features. Chapter Two: A Taxonomy of Japanese Paradigmatic Features and the Issues Arising for Translation into English The Japanese and English languages have significant lexical and morpho-syntactic differences, which I contend give rise to potentially problematic translation issues. The chapter begins by differentiating cultural and linguistic features and explaining why the thesis will focus on the latter. The rest of the chapter presents a detailed analysis of ST exemplars of the most significant of the paradigmatic (lexical) features. Seidensticker and Holman's translations are analysed to determine how they have addressed the translation issues arising from these features. Chapter Three: A Taxonomy of Japanese Syntagmatic Features and the Issues Arising for Translation into English This chapter continues the analysis of linguistic differences between Japanese and English in the context of literary translation. Here the focus is on the syntagmatic (structural)features of Japanese in comparison with English, again examining examples from the ST and comparing how the translators address the issues a

Chapter One: Literary Translation Studies, Japanese-to-English Translation, and Izu no odoriko This introductory chapter explores aspects of Translation Studies relevant to Japanese-to-English literary translation. I employ extended metaphors from the case study, Kawabata Yasunari's novella Izu no odoriko,to re-illuminate perennial TS issues such as equivalence, 'style' and disambiguation, contrasting the translating approaches of Edward G. Seidensticker and J. Martin Holman. The chapter concludes with an outline of the investigative path I followed in analysing the sourcetext (ST) and comparing it with the target texts (TTs): the English translations. I explain the thesis's systematic corpus approach in using an NVivo database to establish a set of potentially problematic translation issues that arise out of the interaction of source language-target language (SL-TL) features. Chapter Two: A Taxonomy of Japanese Paradigmatic Features and the Issues Arising for Translation into English The Japanese and English languages have significant lexical and morpho-syntactic differences, which I contend give rise to potentially problematic translation issues. The chapter begins by differentiating cultural and linguistic features and explaining why the thesis will focus on the latter. The rest of the chapter presents a detailed analysis of ST exemplars of the most significant of the paradigmatic (lexical) features. Seidensticker and Holman's translations are analysed to determine how they have addressed the translation issues arising from these features. Chapter Three: A Taxonomy of Japanese Syntagmatic Features and the Issues Arising for Translation into English This chapter continues the analysis of linguistic differences between Japanese and English in the context of literary translation. Here the focus is on the syntagmatic (structural)features of Japanese in comparison with English, again examining examples from the ST and comparing how the translators address the issues a

Chapter One: Literary Translation Studies, Japanese-to-English Translation, and Izu no odoriko This introductory chapter explores aspects of Translation Studies relevant to Japanese-to-English literary translation. I employ extended metaphors from the case study, Kawabata Yasunari's novella Izu no odoriko,to re-illuminate perennial TS issues such as equivalence, 'style' and disambiguation, contrasting the translating approaches of Edward G. Seidensticker and J. Martin Holman. The chapter concludes with an outline of the investigative path I followed in analysing the sourcetext (ST) and comparing it with the target texts (TTs): the English translations. I explain the thesis's systematic corpus approach in using an NVivo database to establish a set of potentially problematic translation issues that arise out of the interaction of source language-target language (SL-TL) features. Chapter Two: A Taxonomy of Japanese Paradigmatic Features and the Issues Arising for Translation into English The Japanese and English languages have significant lexical and morpho-syntactic differences, which I contend give rise to potentially problematic translation issues. The chapter begins by differentiating cultural and linguistic features and explaining why the thesis will focus on the latter. The rest of the chapter presents a detailed analysis of ST exemplars of the most significant of the paradigmatic (lexical) features. Seidensticker and Holman's translations are analysed to determine how they have addressed the translation issues arising from these features. Chapter Three: A Taxonomy of Japanese Syntagmatic Features and the Issues Arising for Translation into English This chapter continues the analysis of linguistic differences between Japanese and English in the context of literary translation. Here the focus is on the syntagmatic (structural)features of Japanese in comparison with English, again examining examples from the ST and comparing how the translators address the issues a

TRPC6 is a non-voltage-gated Ca(2+) entry/depolarization channel associated with vascular tone regulation and remodeling. Expressed TRPC6 channel responds to both neurohormonal and mechanical stimuli, the mechanism for which remains controversial. In this study, we examined the possible interactions of receptor and mechanical stimulations in activating this channel using the patch clamp technique. In HEK293 cells expressing TRPC6, application of mechanical stimuli (hypotonicity, shear, 2,4,6-trinitrophenol) caused, albeit not effective by themselves, a prominent potentiation of cationic currents (I(TRPC6)) induced by a muscarinic receptor agonist carbachol. This effect was insensitive to a tarantula toxin GsMTx-4 (5 mumol/L). A similar extent of mechanical potentiation was observed after activation of I(TRPC6) by GTPgammaS or a diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol (OAG). Single TRPC6 channel activity evoked by carbachol was also enhanced by a negative pressure added in the patch pipette. Mechanical potentiation of carbachol- or OAG-induced I(TRPC6) was abolished by small interfering RNA knockdown of cytosolic phospholipase A(2) or pharmacological inhibition of omega-hydroxylation of arachidonic acid into 20-HETE (20-hydroxyeicosatetraenoic acid). Conversely, direct application of 20-HETE enhanced both OAG-induced macroscopic and single channel TRPC6 currents. Essentially the same results were obtained for TRPC6-like cation channel in A7r5 myocytes, where its activation by noradrenaline or Arg8 vasopressin was greatly enhanced by mechanical stimuli via 20-HETE production. Furthermore, myogenic response of pressurized mesenteric artery was significantly enhanced by weak receptor stimulation dependently on 20-HETE production. These results collectively suggest that simultaneous operation of receptor and mechanical stimulations may synergistically amplify transmembrane Ca(2+) mobilization through TRPC6 activation, thereby enhancing the vascular tone via p

Udgivelsesdato: 2008-Sep-2, Background/Aims: The roles of intercellular communication and T-type versus L-type voltage-dependent Ca(2+) channels (VDCCs) in conducted vasoconstriction to local KCl-induced depolarization were investigated in mesenteric arterioles. Methods: Ratiometric Ca(2+) imaging (R) using Fura-PE3 with micro-ejection of depolarizing KCl solution and VDCC blockers, and immunohistochemical and RT-PCR techniques were applied to isolated rat mesenteric terminal arterioles (n = 71 from 47 rats; intraluminal diameter: 24 +/- 1 mum; length: 550-700 mum). Results: Local application of KCl (at 0 mum) led to local (DeltaR = 0.54) and remote (DeltaR = 0.17 at 500 mum) increases in intracellular Ca(2+). Remote Ca(2+) responses were inhibited by the gap junction uncouplers carbenoxolone and palmitoleic acid. Ca(V)1.2, Ca(V)3.1 and Ca(V)3.2 channels were immunolocalized in vascular smooth muscle cells and Ca(V)3.2 in adjacent endothelial cells. Local and remote Ca(2+) responses were inhibited by bath application of L- and T-type blockers [nifedipine, NNC 55-0396 and R(-)-efonidipine]. Remote Ca(2+) responses (500 mum) were not affected by abolishing Ca(2+) entry at an intermediate position on the arterioles (at 200-300 mum) using micro-application of VDCC blockers. Conclusion: Both L- and T-type channels mediate Ca(2+) entry during conducted vasoconstriction to local KCl in mesenteric arterioles. However, these channels do not participate in the conduction process per se.

Udgivelsesdato: 2008-Sep-2, Background/Aims: The roles of intercellular communication and T-type versus L-type voltage-dependent Ca(2+) channels (VDCCs) in conducted vasoconstriction to local KCl-induced depolarization were investigated in mesenteric arterioles. Methods: Ratiometric Ca(2+) imaging (R) using Fura-PE3 with micro-ejection of depolarizing KCl solution and VDCC blockers, and immunohistochemical and RT-PCR techniques were applied to isolated rat mesenteric terminal arterioles (n = 71 from 47 rats; intraluminal diameter: 24 +/- 1 mum; length: 550-700 mum). Results: Local application of KCl (at 0 mum) led to local (DeltaR = 0.54) and remote (DeltaR = 0.17 at 500 mum) increases in intracellular Ca(2+). Remote Ca(2+) responses were inhibited by the gap junction uncouplers carbenoxolone and palmitoleic acid. Ca(V)1.2, Ca(V)3.1 and Ca(V)3.2 channels were immunolocalized in vascular smooth muscle cells and Ca(V)3.2 in adjacent endothelial cells. Local and remote Ca(2+) responses were inhibited by bath application of L- and T-type blockers [nifedipine, NNC 55-0396 and R(-)-efonidipine]. Remote Ca(2+) responses (500 mum) were not affected by abolishing Ca(2+) entry at an intermediate position on the arterioles (at 200-300 mum) using micro-application of VDCC blockers. Conclusion: Both L- and T-type channels mediate Ca(2+) entry during conducted vasoconstriction to local KCl in mesenteric arterioles. However, these channels do not participate in the conduction process per se.

SCOPUS: ar.j, info:eu-repo/semantics/published

SCOPUS: ar.j, info:eu-repo/semantics/published

Shiga Shigetaka (1863-1927) is generally known among scholars of Japanese intellectual history as the pioneering advocate of kokusui shugi (maintenance of Japan's cultural identity), a theory which called for spiritual solidarity in the late 1880s when Japan was facing increasing pressure from the West. He is also regarded as an intellectual opponent of his contemporary, journalist Tokutomi Soho (1863-1957), who advocated heimin shugi, total modernisation of Japan. Their so-called rivalry has been understood as Shigetaka being "conservative" and Soho, "progressive", despite the many parallels in their ideas regarding the necessity for industrialisation of Japan: the myth has been created that Shigetaka's ideas are synonymous with those of the "conservative" intellectuals, particularly the "Confucian" scholars (jukyo shugi sha). In fact, Shigetaka strongly rejected the "conservative" label and criticised the "Confucian" scholars when their influence culminated in the promulgation of the Imperial Rescript on Education in 1890 and also when the National Morality Movement gained nation-wide support after 1910. However, his criticism of them has not been sufficiently studied and existing discussions of his thought predominantly focus on the kokusui issue. Other studies deal with Shigetaka as geographer, political activist, and global traveller, but tend to be rather sketchy. Above all, they do not concern themselves with his thoughts on education, which are particularly significant in light of his opposition to the "Confucian" scholars' attempts to achieve national moral control. Despite his opposition, there has been another longstanding myth about him: his kokusui advocacy and his purpose of promotion as well as popularisation of the study of the geography have been interpreted as leading towards Japan's later imperialism. One of the purposes of this study is to challenge these two myths, (Shigetaka as a "conservative" intellectual and Shigetaka as a forerunner of impe

Shiga Shigetaka (1863-1927) is generally known among scholars of Japanese intellectual history as the pioneering advocate of kokusui shugi (maintenance of Japan's cultural identity), a theory which called for spiritual solidarity in the late 1880s when Japan was facing increasing pressure from the West. He is also regarded as an intellectual opponent of his contemporary, journalist Tokutomi Soho (1863-1957), who advocated heimin shugi, total modernisation of Japan. Their so-called rivalry has been understood as Shigetaka being "conservative" and Soho, "progressive", despite the many parallels in their ideas regarding the necessity for industrialisation of Japan: the myth has been created that Shigetaka's ideas are synonymous with those of the "conservative" intellectuals, particularly the "Confucian" scholars (jukyo shugi sha). In fact, Shigetaka strongly rejected the "conservative" label and criticised the "Confucian" scholars when their influence culminated in the promulgation of the Imperial Rescript on Education in 1890 and also when the National Morality Movement gained nation-wide support after 1910. However, his criticism of them has not been sufficiently studied and existing discussions of his thought predominantly focus on the kokusui issue. Other studies deal with Shigetaka as geographer, political activist, and global traveller, but tend to be rather sketchy. Above all, they do not concern themselves with his thoughts on education, which are particularly significant in light of his opposition to the "Confucian" scholars' attempts to achieve national moral control. Despite his opposition, there has been another longstanding myth about him: his kokusui advocacy and his purpose of promotion as well as popularisation of the study of the geography have been interpreted as leading towards Japan's later imperialism. One of the purposes of this study is to challenge these two myths, (Shigetaka as a "conservative" intellectual and Shigetaka as a forerunner of impe

Shiga Shigetaka (1863-1927) is generally known among scholars of Japanese intellectual history as the pioneering advocate of kokusui shugi (maintenance of Japan's cultural identity), a theory which called for spiritual solidarity in the late 1880s when Japan was facing increasing pressure from the West. He is also regarded as an intellectual opponent of his contemporary, journalist Tokutomi Soho (1863-1957), who advocated heimin shugi, total modernisation of Japan. Their so-called rivalry has been understood as Shigetaka being "conservative" and Soho, "progressive", despite the many parallels in their ideas regarding the necessity for industrialisation of Japan: the myth has been created that Shigetaka's ideas are synonymous with those of the "conservative" intellectuals, particularly the "Confucian" scholars (jukyo shugi sha). In fact, Shigetaka strongly rejected the "conservative" label and criticised the "Confucian" scholars when their influence culminated in the promulgation of the Imperial Rescript on Education in 1890 and also when the National Morality Movement gained nation-wide support after 1910. However, his criticism of them has not been sufficiently studied and existing discussions of his thought predominantly focus on the kokusui issue. Other studies deal with Shigetaka as geographer, political activist, and global traveller, but tend to be rather sketchy. Above all, they do not concern themselves with his thoughts on education, which are particularly significant in light of his opposition to the "Confucian" scholars' attempts to achieve national moral control. Despite his opposition, there has been another longstanding myth about him: his kokusui advocacy and his purpose of promotion as well as popularisation of the study of the geography have been interpreted as leading towards Japan's later imperialism. One of the purposes of this study is to challenge these two myths, (Shigetaka as a "conservative" intellectual and Shigetaka as a forerunner of impe