Real-time detection and continuous monitoring of ER stress in vitro and in vivo by ES-TRAP: evidence for systemic, transient ER stress during endotoxemia

Activity of secreted alkaline phosphatase (SEAP) produced by transfected cells is rapidly down-regulated by endoplasmic reticulum (ER) stress independent of transcriptional regulation. This phenomenon was observed in a wide range of cell types triggered by various ER stress inducers. The magnitude of the decrease in SEAP was proportional to the extent of ER stress and inversely correlated with the induction of endogenous ER stress markers grp78 and grp94. In contrast to SEAP, activity of secreted luciferase was less susceptible to ER stress. The decrease in SEAP activity by ER stress was caused by abnormal post-translational modification, accelerated degradation and reduced secretion of SEAP protein. In transgenic mice constitutively producing SEAP, systemic induction of ER stress led to reduction in serum SEAP. In these mice, administration with lipopolysaccharide caused rapid, transient decrease in serum SEAP activity, and it was correlated with up-regulation of grp78 in several organs including the spleen, lung, kidney, liver and heart. These results elucidated for the first time a possible involvement of transient, systemic ER stress in endotoxemia and provided evidence for usefulness of ER stress responsive alkaline phosphatase for real-time monitoring of ER stress in vitro and in vivo

A study of dependence tendency on friend and parents-child relationship in adolescence

The purpose of this study was to investigate the dependence tendency associated with the interpersonal relationship and the parents-child relationship in adolescence. Subjects were 398 undergraduate students, who were asked to perform a set of questionnaires on dependence tendency and parents-child relationship. The results of this study showed that sex differences, existence of sibling, wether living with parents, and school year affect on their dependence tendency and parents-child relationship

Direct, Continuous Monitoring of Air Pollution by Transgenic Sensor Mice Responsive to Halogenated and Polycyclic Aromatic Hydrocarbons

BACKGROUND: The aryl hydrocarbon receptor (AhR, also called the dioxin receptor) plays crucial roles in toxicologic responses of animals to environmental pollutants, especially to halogenated and polycyclic aromatic hydrocarbons. To achieve direct, continuous risk assessment of air pollution using biological systems, we generated transgenic sensor mice that produce secreted alkaline phosphatase (SEAP) under the control of AhR. METHODS: To characterize responses of the mice to AhR agonists, sensor mice were orally administered 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3MC), benzo[a]pyrene (B[a]P), or β-naphthoflavone (BNF), and serum levels of SEAP were evaluated. To monitor air pollution caused by cigarette smoke, we placed the mice each day in an experimental smoking room, and evaluated activity of serum SEAP for up to 4 days. Activation of AhR in individual organs was also examined by reverse transcription–polymerase chain reaction (RT-PCR) analysis of SEAP. RESULTS: In response to oral exposure to TCDD, sensor mice exhibited dramatic and sustained activation of AhR. The mice also responded sensitively to 3MC, B[a]P, and BNF. Activation of AhR was dose dependent, and the liver was identified as the main responding organ. After exposure to the smoking environment, sensor mice consistently exhibited transient, reversible activation of AhR. RT-PCR analysis of SEAP revealed that activation of AhR occurred predominantly in the lung. CONCLUSION: We are the first laboratory to demonstrate successfully direct, comprehensive monitoring of air pollution using genetically engineered mammals. The established system would be useful for real risk assessment of halogenated and polycyclic aromatic hydrocarbons in the air, especially in smoking environments. KEY WORDS: aromatic hydrocarbon, aryl hydrocarbon receptor (AhR), cigarette smoke, dioxinresponsive element (DRE), secreted alkaline phosphatase (SEAP), transgenic mouse. Enviro

Transcriptional suppression of nephrin in podocytes by macrophages: Roles of inflammatory cytokines and involvement of the PI3K/Akt pathway

AbstractExpression of nephrin, a crucial component of the glomerular slit diaphragm, is downregulated in patients with proteinuric glomerular diseases. Using conditionally immortalized reporter podocytes, we found that bystander macrophages as well as macrophage-derived cytokines IL-1β and TNF-α markedly suppressed activity of the nephrin gene promoter in podocytes. The cytokine-initiated repression was reversible, observed on both basal and inducible expression, independent of Wilms’ tumor suppressor WT1, and caused in part via activation of the phosphatidylinositol-3-kinase/Akt pathway. These results indicated a novel mechanism by which activated macrophages participate in the induction of proteinuria in glomerular diseases

Novel potential of tunicamycin as an activator of the aryl hydrocarbon receptor – dioxin responsive element signaling pathway

AbstractTunicamycin is a well-known inhibitor of protein glycosylation and used as an inducer of endoplasmic reticulum (ER) stress. We found that tunicamycin induced expression of cytochrome P450 1A1 in a dose-dependent manner. Like dioxin, the transcriptional induction was associated with dose-dependent activation of the dioxin responsive element (DRE). This effect was independent of inhibition of protein glycosylation or induction of ER stress. Pharmacological and genetic inhibition of the aryl hydrocarbon receptor (AhR) significantly attenuated activation of DRE by tunicamycin. These results elucidated the novel potential of tunicamycin as an activator of the AhR – DRE signaling pathway

キョウカンセイ ト カンジョウ カクチ ノ カンレンセイ ニツイテノ ケンキュウ

We tested the hypothesis that the emotional awareness of counselors is correlated with their levels of empathy using two scales. The Empathic Experience Scale Revised measured counselors\u27 levels of empathy with regard to two aspects: the level of shared experiences and the level of unshared experiences. The Level of Emotional Awareness Scale was used to evaluate counselors\u27 levels of emotional awareness. Clinical psychologists and graduate students who were studying clinical and counseling psychology were instructed to respond to the utterances of hypothetical clients from the Therapist Response Questionnaire. Results revealed that counselors\u27 levels of emotional awareness were positively related to the extent of their experience in clinical practice; however, empathy was not found to be related with either of these factors. In items for which the clients\u27 utterances were complicated, the level of empathy and emotional awareness were positively related. Therefore, our hypothesis that a greater level of awareness of one\u27s own emotions is associated with a greater level of empathy was supported in situations involving complicated cases. This result suggests the need for awareness training for counselors in graduate schools

Generation of Vascular Endothelial Cells and Hematopoietic Cells by Blastocyst Complementation.

In the case of organ transplantation accompanied by vascular anastomosis, major histocompatibility complex mismatched vascular endothelial cells become a target for graft rejection. Production of a rejection-free, transplantable organ, therefore, requires simultaneous generation of vascular endothelial cells within the organ. To generate pluripotent stem cell (PSC)-derived vascular endothelial cells, we performed blastocyst complementation with a vascular endothelial growth factor receptor-2 homozygous mutant blastocyst. This mutation is embryonic lethal at embryonic (E) day 8.5-9.5 due to an early defect in endothelial and hematopoietic cells. The Flk-1 homozygous knockout chimeric mice survived to adulthood for over 1 year without any abnormality, and all vascular endothelial cells and hematopoietic cells were derived from the injected PSCs. This approach could be used in conjunction with other gene knockouts which induce organ deficiency to produce a rejection-free, transplantable organ in which all the organ's cells and vasculature are PSC derived

The Similarity of the Gelation by Sodium Carbonate and Plant Ash-extracts in the Physical Properties of Imo-Konjac

こんにゃくの伝統的製造法において、凝固剤に草木灰の「灰汁」を利用してきた。その代替として、農家では「炭酸ナトリウム」が利用される。今日、一般に利用されている「水酸化カルシウム」が何故用いられないかについて、こんにゃくの物性特性に及ぼうす影響を、とくに、「のり」のゲル化特性と「飛粉」との関わりを中心に検討し、考察した。凝固剤「炭酸ナトリウム」は、芋こんにゃく特有の表面のやわらかい弾力と粘性と硬さを有する物性を形成し、この特性は、とくに「飛粉」が混在する場合において顕著に発現することが明らかになった。それは凝固剤「灰汁」のゲル化特性と極めて類似していた。また、「灰汁」は使用する濃度によって、物性特性が大きく影響されないが、「炭酸ナトリウム」においても同様の特性を示し、いわゆる、「のり」の状態によって凝固剤使用量を加減することが可能な、使いやすさの利点が「灰汁」と類似していることも明らかになった。このような特徴は、「水酸化カルシウム」を凝固剤とした場合、「飛粉」混在で物性が低下し、使用濃度によっても影響されるなど、「炭酸ナトリウム」「灰汁」と異なる挙動を示すことが明らかになった。また、「のり」の物性についての検討からも、こんにゃくに及ぼす影響に反映していることが認められた。凝固剤のゲル化の形成と特性にpH以外の要因として、「飛粉」が重要な作用を果たしていることが示唆された

The Similarity of the Gelation by Sodium Carbonate and Plant Ash-extracts in the Physical Properties of Imo-Konjac

こんにゃくの伝統的製造法において、凝固剤に草木灰の「灰汁」を利用してきた。その代替として、農家では「炭酸ナトリウム」が利用される。今日、一般に利用されている「水酸化カルシウム」が何故用いられないかについて、こんにゃくの物性特性に及ぼうす影響を、とくに、「のり」のゲル化特性と「飛粉」との関わりを中心に検討し、考察した。凝固剤「炭酸ナトリウム」は、芋こんにゃく特有の表面のやわらかい弾力と粘性と硬さを有する物性を形成し、この特性は、とくに「飛粉」が混在する場合において顕著に発現することが明らかになった。それは凝固剤「灰汁」のゲル化特性と極めて類似していた。また、「灰汁」は使用する濃度によって、物性特性が大きく影響されないが、「炭酸ナトリウム」においても同様の特性を示し、いわゆる、「のり」の状態によって凝固剤使用量を加減することが可能な、使いやすさの利点が「灰汁」と類似していることも明らかになった。このような特徴は、「水酸化カルシウム」を凝固剤とした場合、「飛粉」混在で物性が低下し、使用濃度によっても影響されるなど、「炭酸ナトリウム」「灰汁」と異なる挙動を示すことが明らかになった。また、「のり」の物性についての検討からも、こんにゃくに及ぼす影響に反映していることが認められた。凝固剤のゲル化の形成と特性にpH以外の要因として、「飛粉」が重要な作用を果たしていることが示唆された