Catecholamines Facilitate Fuel Expenditure and Protect Against Obesity via a Novel Network of the Gut-Brain Axis in Transcription Factor Skn-1-deficient Mice

AbstractTaste signals and nutrient stimuli sensed by the gastrointestinal tract are transmitted to the brain to regulate feeding behavior and energy homeostasis. This system is referred to as the gut-brain axis. Here we show that both brush cells and type II taste cells are eliminated in the gastrointestinal tract of transcription factor Skn-1 knockout (KO) mice. Despite unaltered food intake, Skn-1 KO mice have reduced body weight with lower body fat due to increased energy expenditure. In this model, 24-h urinary excretion of catecholamines was significantly elevated, accompanied by increased fatty acid β-oxidation and fuel dissipation in skeletal muscle and impaired insulin secretion driven by glucose. These results suggest the existence of brain-mediated energy homeostatic pathways originating from brush cells and type II taste cells in the gastrointestinal tract and ending in peripheral tissues, including the adrenal glands. The discovery of food-derived factors that regulate these cells may open new avenues the treatment of obesity and diabetes.Research ContextTaste signals and nutrient stimuli sensed by the gastrointestinal tract are transmitted to the brain to regulate feeding behavior and energy homeostasis along the gut-brain axis. We propose the concept that taste-receiving cells in the oral cavity and/or food-borne chemicals-receiving brush cells in the gut are involved in regulation of the body weight and adiposity via the brain. The discovery of food-derived factors that regulate these cells may open new avenues for the treatment of obesity and diabetes

A Conversation Analysis Study of Speaking Rate Control by a Dysarthric Patient : A Case in which Dysarthria Improved in Conversation Continuity and Length of Utterances through Using a Pacing Board

ペーシングボードの使用により発話明瞭度が向上したdysarthria例に対して,会話分析の立場から「会話の伝達率」と「1発話の長さ」を検討し,主に以下の結果を得た.(1)ペーシングボード非使用時の会話伝達率は54.0%であったのに比し,使用時では98.1%と向上していた.(2)1発話の長さに関しては,モーラ数による比較ではペーシングボード非使用時の平均モーラ数は5.9,使用時は11.9であった.また平均文節数は非使用時1.4,使用時2.8と両指標とも約2倍に延長していた.以上の結果に基づいて,dysarthriaにおける発話速度調節訓練について会話分析から検討を加えた.Conversational transmissibility and length of utterances were studied in a　dysarthric patient who improved in intelligibility　because of use of a pacing board.The following results were obtained : (1)Conversational transmissibility was 54% when the pacing board was not used, whereas　transmissibility improved to 98.1 % when the board was used. (2) Comparison of the utterance length was made based on the number of mora, in which the average mora was 5.9 without use of the pacing board and 11.9 with use of the board. The number of average segments was 1.4 without　the board as opposed to 2.8 with the board. In both cases the indices increased by　nearly twofold when the pacing board was used. Based on these results, discussion　was held on the training of speaking rate control by the dysarthric speaker based on　conversation analysis

Oral Cancer Screening Based on Methylation Frequency Detection in hTERT Gene Using Electrochemical Hybridization Assay via a Multi‐electrode Chip Coupled with Ferrocenylnaphthalene Diimide

Ferrocenylnaphthalene diimide‐based electrochemical hybridization assay via a multi‐electrode chip was applied to detect the methylation frequency in the promoter region of human telomerase reverse transcriptase (hTERT) gene for clinical samples from tissues, local exfoliated oral cells from a lesion, or from entire oral cavity after their methylation specific PCRs. These methylation frequencies were increased with cancer progress as the following order: healthy volunteers, oral leukoplakia as precancerous lesion, and oral squamous cell carcinoma (OSCC). Operating characteristic analysis of the obtained current data doesn\u27t only give excellent discrimination ability of OSCC, but also of oral leukoplakia from healthy volunteers for all samples. Sensitivity and specificity was 95% and 90%, respectively, which is a comparable with methods in practical use

アメリカン・ボード宣教師文書 : 同志社女学校女性宣教師を中心として : M. F. デントン書簡訳および註 (4)

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Annotated translations of the correspondence of American Board Missionaries : focused on women missionary teachers at Doshisha Girls\u27 School : Mary F. Denton correspondence (2)

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Modulated expression of WFDC1 during carcinogenesis and cellular senescence

Fibroblasts located adjacent to the tumor [cancer-associated fibroblasts (CAFs)] that constitute a large proportion of the cancer-associated stroma facilitate the transformation process. In this study, we compared the biological behavior of CAFs that were isolated from a prostate tumor to their normal-associated fibroblast (NAF) counterparts. CAFs formed more colonies when seeded at low cell density, exhibited a higher proliferation rate and were less prone to contact inhibition. In contrast to the general notion that high levels of α-smooth muscle actin serve as a marker for CAFs, we found that prostate CAFs express it at a lower level compared with prostate NAFs. Microarray analysis revealed a set of 161 genes that were altered in CAFs compared with NAFs. We focused on whey acidic protein four-disulfide core domain 1 (WFDC1), a known secreted protease inhibitor, and found it to be downregulated in the CAFs. WFDC1 expression was also dramatically downregulated in highly prolific mesenchymal cells and in various cancers including fibrosarcomas and in tumors of the lung, bladder and brain. Overexpression of WFDC1 inhibited the growth rate of the fibrosarcoma HT1080 cell line. Furthermore, WFDC1 level was upregulated in senescent fibroblasts. Taken together, our data suggest an important role for WFDC1 in inhibiting proliferation of both tumors and senescent cells. Finally, we suggest that the downregulation of WFDC1 might serve as a biomarker for cellular transformation

アメリカン・ボード宣教師文書 : 同志社女学校女性宣教師を中心として : M. F. デントン書簡訳および註 (5)

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Phospholipase C-β4 Is Essential for the Progression of the Normal Sleep Sequence and Ultradian Body Temperature Rhythms in Mice

BACKGROUND: THE SLEEP SEQUENCE: i) non-REM sleep, ii) REM sleep, and iii) wakefulness, is stable and widely preserved in mammals, but the underlying mechanisms are unknown. It has been shown that this sequence is disrupted by sudden REM sleep onset during active wakefulness (i.e., narcolepsy) in orexin-deficient mutant animals. Phospholipase C (PLC) mediates the signaling of numerous metabotropic receptors, including orexin receptors. Among the several PLC subtypes, the beta4 subtype is uniquely localized in the geniculate nucleus of thalamus which is hypothesized to have a critical role in the transition and maintenance of sleep stages. In fact, we have reported irregular theta wave frequency during REM sleep in PLC-beta4-deficient mutant (PLC-beta4-/-) mice. Daily behavioral phenotypes and metabotropic receptors involved have not been analyzed in detail in PLC-beta4-/- mice, however. METHODOLOGY/PRINCIPAL FINDINGS: Therefore, we analyzed 24-h sleep electroencephalogram in PLC-beta4-/- mice. PLC-beta4-/- mice exhibited normal non-REM sleep both during the day and nighttime. PLC-beta4-/- mice, however, exhibited increased REM sleep during the night, their active period. Also, their sleep was fragmented with unusual wake-to-REM sleep transitions, both during the day and nighttime. In addition, PLC-beta4-/- mice reduced ultradian body temperature rhythms and elevated body temperatures during the daytime, but had normal homeothermal response to acute shifts in ambient temperatures (22 degrees C-4 degrees C). Within the most likely brain areas to produce these behavioral phenotypes, we found that, not orexin, but group-1 metabotropic glutamate receptor (mGluR)-mediated Ca(2+) mobilization was significantly reduced in the dorsal lateral geniculate nucleus (LGNd) of PLC-beta4-/- mice. Voltage clamp recordings revealed that group-1 mGluR-mediated currents in LGNd relay neurons (inward in wild-type mice) were outward in PLC-beta4-/- mice. CONCLUSIONS/SIGNIFICANCE: These lines of evidence indicate that impaired LGNd relay, possibly mediated via group-1 mGluR, may underlie irregular sleep sequences and ultradian body temperature rhythms in PLC-beta4-/- mice

アメリカン・ボード宣教師文書：同志社女学校女性宣教師を中心として〈M. F. デントン書簡：訳および註〉（10）

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