Integrin αPS3/βν-mediated phagocytosis of apoptotic cells and bacteria in Drosophila

13301甲第4176号博士（医学）金沢大学博士論文本文Full 以下に掲載：Jourbal of Biological Chemistry 288(15) pp.10374-10380 2014. ASBMB. 共著者：Saori Nonaka, Kaz Nagaosa, Toshinobu Mori, Akiko Shiratsuchi, Yoshinobu Nakanish

Negative effects of positive stereotypes: Reconsidering the experiments by Siy and Cheryan (2016)

In study 1, based on the findings of Siy and Cheryan (2016), we investigated whether female targets who heard a positive stereotype of women would perceive the stereotype holder as a prejudiced person and whether two factors, a sense of depersonalization and belief of being negatively stereotyped, would mediate the process. In Study 2, we investigated the moderating effect of benevolent sexism on participant attitudes. Using a sample of female university students in Japan, we found that hearing a positive stereotype induced a sense of depersonalization as well as the perception of being a target of prejudice. However, we did not find any well-explained mediating or moderating effects. Further research should investigate the negative effects of positive stereotypes specifying the gender of a stereotype holder (i.e., a member of out-group or in-group) and measuring the perceived traits (e.g. warmth) of the stereotype holder.本論文は，2018年度に広島大学教育学部で開講された心理学課題演習において，第1著者の指導により第2著者から第6著者が実施した研究をもとに執筆したものである。研究の一部は第2著者から第5著者により中国四国心理学会第74回大会学部生研究発表会において報告された。また，本研究はJSPS科研費JP18K03007の助成を受けた

Assessment of drug needs and contributions of pharmacists in the aftermath of the 2011 triple disaster in Fukushima, Japan: A combined analysis

After a major disaster, drug logistics are crucial for maintaining medical care. Although pharmacists play a vital role in healthcare institutions, their role is not well defined, and their recognition from other healthcare professionals is lacking. This was evident at Minamisoma Municipal General Hospital in Fukushima, Japan, which was affected by the Great East Japan earthquake, tsunami, and nuclear power plant accident. The supply of drugs and related information was severely disrupted. In response, two pharmacists were interviewed and the data was analyzed through a thematic approach. Additionally, prescription data collected by pharmacists was analyzed quantitatively. The results from the qualitative survey showed that pharmacists made efforts to supply drugs and collect information, despite facing various psychological challenges, such as confidence, responsibility, anguish, and conflicts. The “leadership” of the hospital's upper managers was instrumental in supporting the pharmacists. The prescription data revealed that drug supply continued for approximately one month without interruption, and the demand for antihypertensive and psychiatric drugs increased. A majority (72.3 %) of the patients (N = 3,518) were 60 years of age or older, which might have contributed to the demand for chronic disease drugs. This study provides an example of the role of pharmacists and drug logistics during major disaster situations, including nuclear accidents

Signaling pathway for phagocyte priming upon encounter with apoptotic cells

The phagocytic elimination of cells undergoing apoptosis is an evolutionarily conserved innate immune mechanism for eliminating unnecessary cells. Previous studies showed an increase in the level of engulfment receptors in phagocytes after the phagocytosis of apoptotic cells, which leads to the enhancement of their phagocytic activity. However, precise mechanisms underlying this phenomenon require further clarification. We found that the pre-incubation of a Drosophila phagocyte cell line with the fragments of apoptotic cells enhanced the subsequent phagocytosis of apoptotic cells, accompanied by an augmented expression of the engulfment receptors Draper and integrin αPS3. The DNA-binding activity of the transcription repressor Tailless was transiently raised in those phagocytes, depending on two partially overlapping signal-transduction pathways for the induction of phagocytosis as well as the occurrence of engulfment. The RNAi knockdown of tailless in phagocytes abrogated the enhancement of both phagocytosis and engulfment receptor expression. Furthermore, the hemocytespecific RNAi of tailless reduced apoptotic cell clearance in Drosophila embryos. Taken together, we propose the following mechanism for the activation of Drosophila phagocytes after an encounter with apoptotic cells: two partially overlapping signal-transduction pathways for phagocytosis are initiated; transcription repressor Tailless is activated; expression of engulfment receptors is stimulated; and phagocytic activity is enhanced. This phenomenon most likely ensures the phagocytic elimination of apoptotic cells by stimulated phagocytes and is thus considered as a mechanism to prime phagocytes in innate immunity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.Embargo Period 12 month

Mortality risk associated with nuclear disasters depends on the time during and following evacuation of hospitals near nuclear power plants: An observational and qualitative study

This study aimed to examine the factors correlated with emergency evacuations on patients’ prognosis in hospitals severely affected by the Fukushima Daiichi nuclear power plant (FDNPP) accident in March 2011, and to recommend measures mitigating potential health risks among them in future disasters. Seven hospitals within a 20-km radius of the FDNPP were designated as the evacuation zone, of which three hospitals located within a 5-km radius were examined. Information regarding hospital emergency evacuation among the three hospitals from previous literature and official reports were integrated and interview outcomes of staff at each hospital were qualitatively analyzed using thematic analysis. Our thematic analysis identified four themes: insufficient preparedness for disaster, difficulty of patient evacuation, insufficient materials, and insufficient information. Comparison of the three hospitals located within a 5-km radius of the FDNPP revealed that hospitals with several patients or those with a high proportion of bedridden or critically ill patients faced more difficulty in emergency evacuation and experienced higher fatalities. In addition to individual evacuation plans, for future preparedness, external and public organizations should prepare disaster responses such as procedures to integrate information on the status of each medical facility and measures to support them individually

新規内因性リガンドによる感染非依存の免疫活性化機構の解析

金沢大学医薬保健研究域薬学系 / 安田女子大学ショウジョウバエにおいて、Tollの新規内因性リガンドSpz5は、既知のTollリガンドSpzとは異なり、プロテアーゼによる切断を受けずにTollリガンドとして働くこと、Spz5-Tollの下流ではdMyd88が情報伝達分子として働くことがわかった。しかし、当初の予想に反して、ショウジョウバエ幼虫をピンセットでつまむと抗菌ペプチドが産生されるという申請者のグループが独自に開発した感染非依存の免疫の異常活性化のモデル系へのSpz5の関与は示せず、感染非依存の免疫活性化機構の全容は解明はできなかった。その代わりに、Spz5はSpzと協調して、ショウジョウバエの正常な個体発生に働くことが示された。We demostrated that Spz5 works as a Toll ligand without clevage by protease in Drosophila although Spz, a famous Toll ligand, needs activation by protease. And, dMyd88 was identified as a signal transducer in the downstream of Spz5-Toll. However, we couldn\u27t show the requirement of Spz5 in infection-independent expression of antimicrobial peptides in larvae after pinching, and the mechanism of infection-independenet immunity remains unclear. Instead of that, we showed genetic interaction between Spz5 and Spz in the developmental process of Drosophila.研究課題/領域番号:18K15181, 研究期間(年度):2018-04-01 – 2020-03-31出典：「新規内因性リガンドによる感染非依存の免疫活性化機構の解析」研究成果報告書　課題番号18K15181（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-18K15181/18K15181seika/)を加工して作

A new system to evaluate characteristics of Niemann-Pick C1 Like 1-mediated cholesterol transport using Xenopus laevis oocytes

Niemann-Pick C1 Like 1 (NPC1L1) is known to be involved in the intestinal absorption of cholesterol. For evaluating the function of NPC1L1, cell lines such as Caco-2, Madin-Darby canine kidney (MDCK) II, and McA-RH7777 have been used in previous studies, but the detailed molecular mechanism of transport has not been elucidated. In this study, the characteristics of cholesterol transport via NPC1L1 were investigated using a Xenopus laevis oocyte expression system in addition to a conventional cell line with stable expression. The transport activity of cholesterol uptake was increased in NPC1L1-overexpressed MDCK cells compared with that in mock cells, but MDCK cells expressed endogenous NPC1L1 and had high cholesterol transport activity. On the other hand, cRNA-injected oocytes expressed NPC1L1 after culturing for 5-6 days. The transport activity of cholesterol uptake was increased in NPC1L1 cRNA-injected oocytes compared with that in water-injected oocytes. In addition, the uptake of cholesterol was decreased in the presence of ezetimibe, an NPC1L1 inhibitor, in cRNA-injected oocytes but not in control oocytes, indicating that endogenous NPC1L1 is not expressed in oocytes. Furthermore, cholesterol uptake was substantially decreased in NPC1L1 L216A cRNA-injected oocytes compared with that in NPC1L1 cRNA-injected oo-cytes, indicating that leucine at position 216 of NPC1L1 is important for cholesterol transport and that an oocyte expression system is useful for mutant analysis. These results indicate that the oocyte expression system is useful for evaluating the characteristics of NPC1L1-mediated cholesterol transport and may contribute to the elucidation of the detailed molecular mechanism of cholesterol transport via NPC1L1