Effects of self-awakening on sleep structure and sleep inertia during or after the short nap

本研究の目的は, 短時期仮眠における自己覚醒の企図が, 睡眠構造および睡眠慣性に及ぼす影響を検討することである。実験は, 自分で目覚める自己覚醒条件と,実験者が強制的に覚醒させる強制覚醒条件の参加者内比較計画で行った。覚醒水準の評価には, 聴覚オドボール課題により算出された事象関連電位のP300と課題正反応時間,Visual Analog Scale (Vas)による主観的覚醒水準評定値を用いた。睡民構造の詳細な検討のために,Hori et al. (1994)の脳波段階判定(9段階)を用いた。実験参加者は,大学生・大学院生14名であった。実験参加者は,4minの聴覚オドボール課題と1minのVAS評定からなる計5分間の課題を2セッション(計10分間)行った。その後,約20分間の仮眠をとり,覚醒後に同様の課題を6セッション(計30分間)行った。本研究の結果,自己覚醒を用いて出眠した場合には,強制覚醒の場合と比べて,P300振幅は大きくなり,主観的眠気は低減していた。また,自己覚醒を意図した場合には,睡眠構造が浅くなる傾向があった。これらの結果から,強制覚醒よりも自己覚醒をもちいた仮眠が,午後の眠気を抑える方法として有効であることが示された。(518語)The aim of this study was the investigation of the effects of self-awakening on sleep inertia and sleep structure at the short nap. The participants were take part in the self-awakening and forced-awakening condition. In the self-awakening condition, participant woke up by themselves. However, experimenter in the forced-awakening condition waked participants up. The physiological arousal level and subjective sleepiness were evaluated by P300 of the event related potential (ERP) and visual analog scale (VAS). For evaluating the sleep structure elaborately, we used the Hori's EEG stages. Participants were 14 healthy college students. They participated the task consist of auditory oddball task (4 min) and VAS rating (1 min). Participant carried out two sessions (10 min) before the nap. Thereafter, they took a short nap around 20 min. After the nap, they carried out six sessions (30 min) again. P300 amplitude was lower after forced -awakening than self-awakening. On the other hand, subjective sleepiness was greater after the forced-awakening than self-awakening. And sleep structure was deeper during the forced-awakening than self-awakening. Those results suggest that a short nap with self-awakening was more useful than with forced-awakening

Senescence-inducing stress promotes proteolysis of phosphoglycerate mutase via ubiquitin ligase Mdm2.

細胞老化から癌化への変換のカギとなる解糖系制御機構解明に成功 -代謝を標的とした新しい抗がん剤開発に期待-. 京都大学プレスリリース. 2014-02-24.Despite the well-documented clinical significance of the Warburg effect, it remains unclear how the aggressive glycolytic rates of tumor cells might contribute to other hallmarks of cancer, such as bypass of senescence. Here, we report that, during oncogene- or DNA damage-induced senescence, Pak1-mediated phosphorylation of phosphoglycerate mutase (PGAM) predisposes the glycolytic enzyme to ubiquitin-mediated degradation. We identify Mdm2 as a direct binding partner and ubiquitin ligase for PGAM in cultured cells and in vitro. Mutations in PGAM and Mdm2 that abrogate ubiquitination of PGAM restored the proliferative potential of primary cells under stress conditions and promoted neoplastic transformation. We propose that Mdm2, a downstream effector of p53, attenuates the Warburg effect via ubiquitination and degradation of PGAM

Metabolism of Skin-Absorbed Resveratrol into Its Glucuronized Form in Mouse Skin

<div><p>Resveratrol (RESV) is a plant polyphenol, which is thought to have beneficial metabolic effects in laboratory animals as well as in humans. Following oral administration, RESV is immediately catabolized, resulting in low bioavailability. This study compared RESV metabolites and their tissue distribution after oral uptake and skin absorption. Metabolomic analysis of various mouse tissues revealed that RESV can be absorbed and metabolized through skin. We detected sulfated and glucuronidated RESV metabolites, as well as dihydroresveratrol. These metabolites are thought to have lower pharmacological activity than RESV. Similar quantities of most RESV metabolites were observed 4 h after oral or skin administration, except that glucuronidated RESV metabolites were more abundant in skin after topical RESV application than after oral administration. This result is consistent with our finding of glucuronidated RESV metabolites in cultured skin cells. RESV applied to mouse ears significantly suppressed inflammation in the TPA inflammation model. The skin absorption route could be a complementary, potent way to achieve therapeutic effects with RESV.</p></div

RESV metabolism in HepG2 (human hepatocytes), HaCaT (human keratinocytes), and C2C12 (mouse myoblasts).

<p>Cells were treated with 20 or 200 µM RESV for 4 h. After washing with PBS, cells were lysed, and metabolites were extracted and analyzed by LC-MS. Peak areas of RESV–SULF (<b>A</b>), trans-RESV-3-O-GLUC (<b>B</b>) and cis-RESV-3-O-GLUC (<b>C</b>) were normalized by peak areas of spiked internal standards (HEPES and PIPES). Peak areas for each compound are presented as means ± SD of 3 samples (except for HaCaT 200 µM RESV, 2 samples). Statistical significance was assessed using Dunnett’s test: *P<0.05.</p

Detected RESV and DH-RESV metabolites were identified using standard compounds (STD), MS/MS spectrum analysis (MS/MS), or <i>m/z</i> value (MS).

<p>Detected RESV and DH-RESV metabolites were identified using standard compounds (STD), MS/MS spectrum analysis (MS/MS), or <i>m/z</i> value (MS).</p

Absorption efficiency of RESV through mouse skin using 3 bases in different tissues.

<p>One mg of RESV dissolved in ethanol was applied directly (EtOH) or mixed with hydrophilic ointment (HO), macrogol (Ma) or CMC gel (CMC), and swabbed on mouse dorsal skin. After 4 h mice were sacrificed, metabolites were extracted from tissues and analyzed by LC-MS. Peak areas of RESV-SULF (<b>A</b>), trans-RESV-3-O-GLUC (<b>B</b>), cis-RESV-3-O-GLUC (<b>C</b>), DH-RESV-SULF (<b>D</b>), DH-RESV-GLUC (<b>E</b>) and tryptophan (<b>F</b>) were normalized using peak areas of spiked internal standards (HEPES and PIPES). Peak areas for each compound are presented as means ± SD of 3 mice. Statistical significance was assessed with Tukey’s test: *P<0.05.</p

Model of RESV metabolism after oral and transdermal administration.

<p>Arrows indicate metabolism of RESV and dashed arrows indicate predicted metabolism of DH-RESV. Numbers beside the arrows are explained in the text.</p