Impacts of aerosols in East Asia on plants and human health

金沢大学医薬保健研究域医学系mTORC1による生体内での骨髄球系細胞分化における役割を明らかにするため、骨髄球分化の促進が認められるKrasの恒常的な活性化モデルと、mTORC1活性を欠損するRaptor欠損マウスを組み合わせて解析を行った。前年度までの解析で、Raptor欠損は顆粒球分化が阻害されることを見出していたが、Kras活性化状態においても顆粒球分化は著しく阻害されており、骨髄球細胞の終末分化に必須であると考えられた。一方で、骨髄球前駆細胞は顕著に増加していることを見出した。mTORC1はRasシグナルの下流分子であると考えられているが、本研究の結果から、mTORC1抑制による分化抑制効果とKras活性化による骨髄球増殖促進効果がそれぞれ独立して働き、骨髄球前駆細胞を増加させうることが示唆された。　またmTORC1抑制によって細胞に生じる変化を同定するため、mTORC1欠損下で生存する急性骨髄性白血病細胞集団を用いて、表面抗原の網羅的な解析を行った。その結果、mTORC1抑制後には、コントロールの白血病細胞では発現低く、リンパ球系細胞や幹細胞で発現が高いことが報告されている分子が多数発現増加していることを見出した。このことはmTORC1抑制が積極的に細胞分化に影響していることを示唆している。そのいくつかはmRNAレベルで顕著に発現変動しており、mTORC1の変動を介して、翻訳後制御と転写制御の両者で遺伝子発現が変化していると考えられる。今後このような分子の細胞分化における機能とmTORC1との相関を明らかにすることによって、mTORC1による細胞分化制御のメカニズムが明らかになると期待された。研究課題/領域番号:23120703, 研究期間(年度):2011-04-01 – 2013-03-3

卵巣癌に特異的に発現する蛋白の発現調節解析と悪性化・予後への作用機序の解明

金沢大学附属病院卵巣癌は近年増加しているが,リスクファクターとなる生活習慣や環境要因が特定されず,早期発見も難しいため悪性化しやすい癌として知られる。代表者らは卵巣癌で高発現しているLTBP-1L(Latent TGF-β Binding Protein-1L)に着目して解析を進めてきた(Higashi T, et. al.2001)。昨年度までに,LTBP-1L遺伝子のプロモーター配列上に新規の一塩基多型(SNP)を発見し,遺伝子型が転写因子Sp1との結合力に影響し,LTBP-1L蛋白の発現量に有意な差が生じること,さらに特定のSNPの存在が癌症例の術後生存率の低下と相関することを明らかにした(Higashi T, et. al.2006)。本年度は癌細胞で発現したLTBP-1L蛋白の役割と作用機序を明らかにするために, まず卵巣癌培養細胞株JHOM-1において, RNA干渉によるLTBP-1Lの発現抑制を試みた。LTBP-1LのsiRNAを3種類設計し,種々の導入条件をリポフェクション法により検討した結果,LTBP-1L mRNA発現を90%抑制する条件を見い出した。そしてWST-1を用いたアッセイにより,LTBP-1L遺伝子の発現を抑制すると,細胞増殖と生存能が減少することがわかった。したがって,癌細胞で高発現しているLTBP-1Lは,細胞増殖能の活性化を通じて,癌の悪性化に寄与している可能性が示唆された。そこで次にLTBP-1L cDNAの全長を含む4287bpをpIRESneo3ベクター(clontech)に組み込み,細胞でLTBP-1Lを強制発現させるための発現ベクターを構築した。今後この発現ベクターを用いた強制発現実験とRNAi干渉による発現抑制実験により,LTBP-1L機能解析を進めていく必要がある。研究課題/領域番号:18790377, 研究期間(年度):2006 – 2007出典：「卵巣癌に特異的に発現する蛋白の発現調節解析と悪性化・予後への作用機序の解明」研究成果報告書　課題番号18790377（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/grant/KAKENHI-PROJECT-18790377/)を加工して作

A sense of power and system justification: Reexamining van der Troon et al. (2015)

We conducted two studies reexamining the findings of van der Toorn et al. (2015) that a sense of powerlessness fosters system justification (SJ). In Study 1, we used the Sense of Power Scale (Anderson et al., 2012) and found that a sense of powerfulness as well as a sense of powerlessness are positively associated with SJ. In Study 2, after priming participants with a feeling of powerfulness vs. powerlessness, we investigated the mediating effects of emotions on the relationship between sense of power and SJ. Although participants experienced positive emotions in the Powerful condition and negative emotions in the Powerless condition, we did not find any significant effects of emotions on SJ. Further studies are needed to investigate the relationship between a sense of power and SJ using more sophisticated methods.本論文は，2019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5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75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

Dustborne microorganisms in the atmosphere over an Asian dust source region, Dunhuang

金沢大学環日本海域環境研究センターThe dust event injects microorganisms into the atmosphere and could facilitate the dispersal of biological particles affecting leeward ecosystem and human health. In this study, the dustborne microorganisms in the atmosphere over the Taklimakan Desert, Asian dust source, were identified by culture-independent method. Dusts were collect-ed using a balloon at about 800 m above the ground in an Asian dust source region, Dunhuang. After DNAwere directly extracted from the dusts collected filters, 16S and 18S rRNA genes of microorganisms were amplified, cloned, and sequenced. The rDNA sequence data indicated that dust particles include fungi closely related to Rickenella fibula, Ceriporiopsis gilvescens, and bacteria belonging to the genus Brevibacillus, Staphylococcus, Rhodococcus, Delftia, Pseudomonas, and Agrobacterium tumefaciens. These results suggest that dust particles in the atmosphere over Dunhuang could carry these many fungi and bacteria and might play a significant role in leeward ecosystem. © 2009 The Author(s)

Phylogenetic analysis of atmospheric halotolerant bacterial communities at high altitude in an Asian dust (KOSA) arrival region, Suzu City

金沢大学理工研究域物質化学系The microbial communities transported by Asian desert dust (KOSA) events have attracted much attention as bioaerosols because the transported microorganisms are thought to influence the downwind ecosystems in Korea and Japan. However, the atmospheric microbial community has not been investigated at high altitude in the KOSA arrival area. In this study, to estimate the viability and diversity of atmospheric halotolerant bacteria, which are expected to resist to various environmental stresses as well as high salinities, bioaerosol samples were collected at 10 and 600. m above the ground within the KOSA arrival area, Suzu City, Japan, during KOSA events. During the sampling period, the particle numbers at 600. m were higher than those at 10. m, suggesting that large particles of aerosol fall from the high altitude of 600. m to the ground surface. The microorganisms in bioaerosol samples grew in media containing up to 15% NaCl concentrations demonstrating the viability of the halotolerant bacteria in bioaerosol samples. The PCR-DGGE analysis using 16S rDNA revealed that the bacterial species in NaCl-amended cultures were similar to the bacteria detected from the genomic DNA directly extracted from the bioaerosol samples. The 16S rDNA sequences of bacterial communities in bioaerosol samples were classified into 4 phylotypes belonging to the Bacillus cereus or Bacillus subtilis group. The bioaerosol samples collected at 600. m included 2 phylotypes belonging to B. subtilis, and one phylotype among all 4 phylotypes was identical between the samples at 10 and 600. m. In the atmosphere at 600. m, the halotolerant bacterial community was expected to remain viable, and the species composition was expected to include a few species of the genus Bacillus. During this investigation period, these atmospheric bacteria may have been vertically transported to the ground surface, where the long-range KOSA particle transport from China is frequently observed. © 2010 Elsevier B.V

Exacerbation of daily cough and allergic symptoms in adult patients with chronic cough by Asian dust: A hospital-based study in Kanazawa

The health effects associated with Asian dust have attracted attention due to the rapid increase in the number of Asian dust events in East Asia in recent years. The aim of this study was to investigate the associations between Asian dust and daily cough, as well as allergic symptoms, in adult patients who suffer from chronic cough. We enrolled 86 adult patients from Kanazawa University Hospital, Japan, who were diagnosed with asthma, cough variant asthma, atopic cough or a combination of these conditions. From January to June 2011, subjects recorded their symptoms in a diary every day. Asian dust and non-Asian dust periods were defined according to the dust extinction coefficient, measured using the light detection and ranging (LIDAR). The daily levels of total suspended particulates, polycyclic aromatic hydrocarbons (PAHs) and coexisting factors related to allergies, such as the Japanese cedar pollen count, were measured. McNemar\u27s test showed that there were significantly more cough-positive patients during Asian dust periods than during the non-Asian dust period (p = 0.022). In addition, during Asian dust periods when the daily levels of Japanese cedar pollen, Japanese cypress pollen and PAHs were elevated, there were significantly more patients who experienced itchy eyes than during the non-Asian dust period (p < 0.05). On the other hand, there were no significant differences in the allergic symptoms, including sneezing or a runny nose and nasal congestion. This is the first report to show that Asian dust triggers cough and allergic symptoms in adult patients with chronic cough. © 2014 Elsevier Ltd. All rights reserved

Effects of Asian dust on daily cough occurrence in patients with chronic cough: A panel study

Asian dust, known as kosa in Japanese, is a major public health concern. In this panel study, we evaluated the effects of exposure to kosa on daily cough occurrence. The study subjects were 86 patients being treated for asthma, cough variant asthma, or atopic cough in Kanazawa University Hospital from January 2011 to June 2011. Daily mean concentrations of kosa and spherical particles were obtained from light detection and ranging (LIDAR) measurements, and were categorized from Grade 1 (0μg/m3) to 5 (over 100μg/m3). The association between kosa and cough was analyzed by logistic regression with a generalized estimating equation. Kosa effects on cough were seen for all Grades with potential time lag effect. Particularly at Lag 0 (the day of exposure), a dose-response relationship was observed: the odds ratios for Grades 2, 3, 4, and 5 above the referent (Grade 1) were 1.111 (95% confidence interval (CI): 0.995-1.239), 1.171 (95% CI: 1.006-1.363), 1.357 (95% CI: 1.029-1.788), and 1.414 (95% CI: 0.983-2.036), respectively. Among the patients without asthma, the association was higher: the odds ratios for Grades 2, 3, 4 and 5 were 1.223 (95% CI: 0.999-1.497), 1.309 (95% CI: 0.987-1.737), 1.738 (95% CI: 1.029-2.935) and 2.403 (95% CI: 1.158-4.985), respectively. These associations remained after adjusting for the concentration of spherical particles or particulate matter with an aerodynamic diameter of less than 2.5μm (PM2.5). Our findings demonstrate that kosa is an environmental factor which induces cough in a dose-response relationship. © 2014 Elsevier Ltd

Aberrant Glycogen Synthase Kinase 3β Is Involved in Pancreatic Cancer Cell Invasion and Resistance to Therapy

Background and Purpose: The major obstacles to treatment of pancreatic cancer are the highly invasive capacity and resistance to chemo- and radiotherapy. Glycogen synthase kinase 3β (GSK3β) regulates multiple cellular pathways and is implicated in various diseases including cancer. Here we investigate a pathological role for GSK3β in the invasive and treatment resistant phenotype of pancreatic cancer. Methods: Pancreatic cancer cells were examined for GSK3β expression, phosphorylation and activity using Western blotting and in vitro kinase assay. The effects of GSK3β inhibition on cancer cell survival, proliferation, invasive ability and susceptibility to gemcitabine and radiation were examined following treatment with a pharmacological inhibitor or by RNA interference. Effects of GSK3β inhibition on cancer cell xenografts were also examined. Results: Pancreatic cancer cells showed higher expression and activity of GSK3β than non-neoplastic cells, which were associated with changes in its differential phosphorylation. Inhibition of GSK3β significantly reduced the proliferation and survival of cancer cells, sensitized them to gemcitabine and ionizing radiation, and attenuated their migration and invasion. These effects were associated with decreases in cyclin D1 expression and Rb phosphorylation. Inhibition of GSK3β also altered the subcellular localization of Rac1 and F-actin and the cellular microarchitecture, including lamellipodia. Coincident with these changes were the reduced secretion of matrix metalloproteinase-2 (MMP-2) and decreased phosphorylation of focal adhesion kinase (FAK). The effects of GSK3β inhibition on tumor invasion, susceptibility to gemcitabine, MMP-2 expression and FAK phosphorylation were observed in tumor xenografts. Conclusion: The targeting of GSK3β represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer. © 2013 Kitano et al

The research of atmosphere bioaerosol over Antarctica

第2回極域科学シンポジウム/第33回極域生物シンポジウム 11月18日（金） 統計数理研究所 3階セミナー室

Reprint of: Effects of Asian dust on daily cough occurrence in patients with chronic cough: A panel study

金沢大学医薬保健研究域医学系Asian dust, known as kosa in Japanese, is a major public health concern. In this panel study, we evaluated the effects of exposure to kosa on daily cough occurrence. The study subjects were 86 patients being treated for asthma, cough variant asthma, or atopic cough in Kanazawa University Hospital from January 2011 to June 2011. Daily mean concentrations of kosa and spherical particles were obtained from light detection and ranging (LIDAR) measurements, and were categorized from Grade 1 (0 μg/m3) to 5 (over 100 μg/m3). The association between kosa and cough was analyzed by logistic regression with a generalized estimating equation. Kosa effects on cough were seen for all Grades with potential time lag effect. Particularly at Lag 0 (the day of exposure), a dose-response relationship was observed: the odds ratios for Grades 2, 3, 4, and 5 above the referent (Grade 1) were 1.111 (95% confidence interval (CI): 0.995-1.239), 1.171 (95% CI: 1.006-1.363), 1.357 (95% CI: 1.029-1.788), and 1.414 (95% CI: 0.983-2.036), respectively. Among the patients without asthma, the association was higher: the odds ratios for Grades 2, 3, 4 and 5 were 1.223 (95% CI: 0.999-1.497), 1.309 (95% CI: 0.987-1.737), 1.738 (95% CI: 1.029-2.935) and 2.403 (95% CI: 1.158-4.985), respectively. These associations remained after adjusting for the concentration of spherical particles or particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5). Our findings demonstrate that kosa is an environmental factor which induces cough in a dose-response relationship. © 2014 Elsevier B.V.Embargo Period 12 month