著者

Mitsuhiro Machitani Fuminori Sakurai Keisaku Wakabayashi Kosuke Nakatani Kazuo Takayama Masashi Tachibana Hiroyuki Mizuguchi

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.40, no.3, pp.272-277, 2017-03-01 (Released:2017-03-01)

参考文献数

25

被引用文献数

7

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Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated genome engineering technology is a powerful tool for generation of cells and animals with engineered mutations in their genomes. In order to introduce the CRISPR/Cas9 system into target cells, nonviral and viral vectors are often used; however, such vectors trigger innate immune responses associated with production of type I interferons (IFNs). We have recently demonstrated that type I IFNs inhibit short-hairpin RNA-mediated gene silencing, which led us to hypothesize that type I IFNs may also inhibit CRISPR/Cas9-mediated genome mutagenesis. Here we investigated this hypothesis. A single-strand annealing assay using a reporter plasmid demonstrated that CRISPR/Cas9-mediated cleavage efficiencies of the target double-stranded DNA were significantly reduced by IFNα. A mismatch recognition nuclease-dependent genotyping assay also demonstrated that IFNα reduced insertion or deletion (indel) mutation levels by approximately half. Treatment with IFNα did not alter Cas9 protein expression levels, whereas the copy numbers of guide RNA (gRNA) were significantly reduced by IFNα stimulation. These results indicate that type I IFNs significantly reduce gRNA expression levels following introduction of the CRISPR/Cas9 system in the cells, leading to a reduction in the efficiencies of CRISPR/Cas9-mediated genome mutagenesis. Our findings provide important clues for the achievement of efficient genome engineering using the CRISPR/Cas9 system.

著者

瀬谷 司 新開 大史 松本 美佐子

出版者

日本ウイルス学会

雑誌

ウイルス (ISSN:00426857)

巻号頁・発行日

vol.54, no.1, pp.1-8, 2004 (Released:2005-06-17)

参考文献数

39

被引用文献数

4 7

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TLRファミリーはロイシンリッチリピート (LRR) の細胞外領域と細胞内のTIR (Toll/IL-1 R homology) ドメインからなる. TLRはリガンドを認識すると細胞内のTIRドメインへアダプター分子MyD88などをリクルートし, NF-κBとMAP kinaseを活性化し, 最終的にサイトカインやケモカインなどを産生誘導する. 一方, 骨髄性樹状細胞 (mDC) ではTLRによるIFN-β産生やIFN誘導遺伝子の発現, 樹状細胞の成熟化などが誘起されるが, これらはアダプター分子, MyD88非依存性に起こる. TLRのIFN-β産生系としてはdsRNA刺激によるTLR3依存性経路, LPS刺激によるTLR4を介したIFN-β産生経路などがある. リンパ球様樹状細胞 (pDC) ではTLR7/TLR9刺激でIFN-αがMyD88依存性に誘導される. 我々は, 本稿でTLR3, TLR4を介したIFN-β産生に関与するアダプター分子の構造と機能を総説し, 新規のIFN-β誘導経路に言及する. 併せてウイルス成分認識性のTLRがtype I IFNを誘導するシグナル経路, これらの経路とウイルス感染が誘起する抗ウイルスの細胞応答の連携を概説する.

出版者

一般社団法人 情報科学技術協会

雑誌

情報の科学と技術 (ISSN:09133801)

巻号頁・発行日

vol.67, no.3, pp.148-150, 2017-03-01 (Released:2017-03-01)

著者

櫻井 映子

出版者

日本言語学会

雑誌

言語研究 (ISSN:00243914)

巻号頁・発行日

vol.1997, no.112, pp.98-131, 1997-11-25 (Released:2007-10-23)

参考文献数

16

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In the Lithuanian language, prefixing of a simple verb does not always lead to perfective aspect, nor is, there general way of forming imperfective from prefixed perfective verb, such as at an early stage in the development of the Slavonic languages. Therefore, there are only few purely aspectual pairs of verbs with semantically empty prefixes.Most prefixed verbs, which are usually considered as perfective, can be interpreted as morphologically marked terminative (telic) verbs. This is the reason why Lithuanian contains a number of so -called neutral verbs which can express both imperfective and perfective aspect, mainly according to tense. In the Lithuanian tense -aspect system important parts are played by four simple tense forms (in the active voice) and four compound tense forms (both in the active and passive voice).Both perfect and imperfect of the compound tenses have determinations of 'phase', ‹terminalization› and ‹intraterminalization›, respectively. Terminative: aterminative (telic: atelic) character of verbs has an interaction mainly with these basic meanings of perfect and imperfect, which accounts for various aspectual meanings and 'taxis' functions of the Lithuanian compound tenses.

著者

小岩 正樹

出版者

日本建築学会

雑誌

日本建築学会計画系論文集 (ISSN:13404210)

巻号頁・発行日

vol.79, no.696, pp.507-516, 2014-02-28 (Released:2014-07-10)

参考文献数

9

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Jitchu was a famous monk who played an active part in Todai-ji from the late Nara period to the early Heian period. Among his various activities, this study aims to clarify the actual situation of his construction works. In this paper it is revealed that Jitchu played several roles in the construction for not only the management but also planning and site working. This shows that he had broad and respective relations with those who concerning in the construction processes, especially he was linked closely to the Empress Shotoku in several cases.

著者

Lv PEILING Yang HANXIAO Camille GAZEAU Kouichi YASUDA

出版者

公益社団法人 日本セラミックス協会

雑誌

Journal of the Ceramic Society of Japan (ISSN:18820743)

巻号頁・発行日

vol.121, no.1412, pp.338-343, 2013-04-01 (Released:2013-04-01)

参考文献数

21

被引用文献数

3

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Co-sintering was carried out in air at 1350°C for 1 hr to make two types of symmetrical 3-layered laminates. One is PDP (Porous alumina/Dense alumina/Porous alumina) laminate and another is DPD laminate. For the porous alumina layer, the porosity was set to be 20%; however, pore size was changed by adding three sizes of spherical mono-dispersed polymethyl methacrylate particles (5, 15, 30 µm) in raw alumina powder. Young’s modulus measurements revealed that cracking occurred in both PDP and DPD laminates. The stress in the layer was estimated from an elastic calculation by using the mechanical and thermal expansion properties of each monolayer. In consideration of sintering shrinkage and thermal expansion of the layer, it was suggested that cracking occurred in the dense alumina layer during heating from 1000 to 1200°C, and in porous alumina layer during heating from 1200 to 1350°C. The cracking was mainly attributed to the mismatch of sintering shrinkage between the layers. From the discussion, the elastic model gave an explanation to crack formation during co-sintering.

著者

水谷 泰之 大塚 裕之 森島 大雅 藤塚 宣功 片山 雅貴 石川 英樹

出版者

日本膵臓学会

雑誌

膵臓 (ISSN:09130071)

巻号頁・発行日

vol.28, no.6, pp.785-791, 2013 (Released:2014-01-18)

参考文献数

16

被引用文献数

1 8

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患者は65歳,男性.検診で膵管拡張を指摘され当科受診となった.US,単純および造影CTで主膵管拡張を認め,膵実質内に明らかな腫瘤は指摘出来なかった.EUSで主膵管は体尾部で4mmと著明な拡張を認め,その頭側に境界不明瞭で辺縁不整な低エコー領域を認めた.膵上皮内癌を念頭におきERCPを施行した.主膵管は頭体部移行部で限局性狭窄を来たし,尾側膵管は数珠状拡張を呈していた.膵液細胞診の結果は陰性であった.画像診断で腫瘤の認識は困難であったが,膵管像からは膵癌を強く疑い膵頭十二指腸切除を行った.病理学的所見は,主膵管と分枝膵管に低乳頭状増殖を示し,PanIN1からPanIN3に相当する異型上皮の置換性増殖を認めた.検索の限り明らかな浸潤像は確認されなかった.

著者

島野 仁

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.9, pp.1003-1009, 2015 (Released:2015-09-01)

参考文献数

17

被引用文献数

4

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Recent studies suggest that chronic local inflammation and cellular stresses are the key steps in organ defects in obesity-related diseases such as atherosclerosis, diabetes, and fatty liver. We have shown that an excess energy state activates sterol regulatory element-binding protein (SREBP)-1c, a master transcription factor for fatty acid synthesis causing the accumulation of lipids leading to fatty liver, insulin resistance, insulin secretion defects, and dyslipidemia and we clarified their molecular mechanisms. Recently, we shifted focus to the quality aspect of accumulated lipids. It has long been known that saturated and poly-unsaturated fatty acids are atherogenic and anti-atherogenic, respectively. Besides desaturation, we found that the chain-length of fatty acids is another important factor. Elovl6 that we have cloned as an SREBP-1 target is a fatty acid elongase that catalises the last step of fatty acid synthesis. Elovl6 KO mice exhibit obesity and fatty liver on a high energy diet, but unexpectedly were immune to insulin resistance (Nat. Med., 13, 2007, Matsuzaka et al.), atherosclerosis (Arterioscler. Thromb. Vasc. Biol., 31, 2011, Saito et al.) and non-alcoholic steatohepatitis (NASH) pathology including liver damage, ROS, and fibrosis (Hepatology, 56, 2012, Matsuzaka et al.). Elovl6 is crucial for protection against lung fibrosis (Nat. Commun., 4, 2013, Sunaga et al.). These data implicate that fatty acid composition is a new therapeutic target for a variety of chronic metabolic diseases. In this symposium review, a novel strategy for the prevention of life-related diseases will be discussed in the standpoint of application of wet-dry fusion strategies for theoretical and medicinal chemistry.

著者

安藤 洋子

出版者

日本菌学会

雑誌

日本菌学会大会講演要旨集 日本菌学会第57回大会

巻号頁・発行日

pp.18, 2013 (Released:2014-01-28)

著者

外山 茂浩 床井 良徳 井山 徹郎

出版者

自動制御連合講演会

雑誌

自動制御連合講演会講演論文集 第57回自動制御連合講演会

巻号頁・発行日

pp.539-543, 2014 (Released:2016-03-02)

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長岡高専専攻科特別実験で実施しているエンジニアリングデザイン演習の平成26年度のデザインテーマは,レゴマインドストームを用いた中学校技術・家庭科「プログラムによる計測・制御」の教材開発とした.学習指導要領の改訂の後,中学校技術・家庭科において必修化された「プログラムによる計測・制御」への対応を模索されている中学校教員の一助をなすことを目的としたからである.演習の指導概要や,実際に開発した教材,また成果報告会で実際に中学校教員からいただいた感想等について報告する.

著者

石川 雄一

出版者

公益社団法人 精密工学会

雑誌

精密工学会誌 (ISSN:09120289)

巻号頁・発行日

vol.52, no.11, pp.1947-1953, 1986-11-05 (Released:2009-06-30)

参考文献数

10

被引用文献数

1

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It has been said that the internal gears have a higher surface durability as compared with the external gears. Nevertheless, experimental study on the load capacity of internal gears has been extremely few. In the present paper, a new type of four square internal gears running test machine has been developed for investigating the load capacity of internal gear pairs experimentally. And some experiments on the conventional involute tooth profile internal gears have been performed by this testing machine. It is confirmed from these experimental results that the fatigue strength of internal gears increases remarkably with increasing the surface hardness of the internal gear by heat treatment.

著者

森 茂樹 石橋 佑貴也 永野 善己 小川 秀夫

出版者

一般社団法人 日本塑性加工学会

雑誌

塑性と加工 (ISSN:00381586)

巻号頁・発行日

vol.49, no.564, pp.71-75, 2008 (Released:2008-01-30)

参考文献数

8

被引用文献数

1

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In the surface finishing of high-hardness materials such as die materials, it is common for a polishing process to be used. If burnishing is feasible for the surface finishing of a die using a CAD/CAM system and a machining center, it will become a useful working method for the following reasons: (1) reduction of the time required to make work arrangements, (2) improvement of the precision of shape and dimensions, and (3) improvement of the mechanical properties of the surfaces. In this paper, the relationships between working conditions and surface roughness are examined when the finish burnishing of a die material is carried out. The burnishing experiments were performed on prehardened steel with a SiC ceramic ball having a 9.525 mm diameter. Under the conditions of a burnishing force of 400 N and a pitch of 0.195 mm, finish burnishing was performed on a milled surface having a roughness of Ra1.4 μm, and a mirror surface having a roughness of Ra0.1 μm was obtained. In addition, in the case of the product having a free curved surface, a good mirror surface was obtained.

著者

足立 幸志 加藤 康司

出版者

公益社団法人 精密工学会

雑誌

精密工学会誌 (ISSN:09120289)

巻号頁・発行日

vol.60, no.10, pp.1410-1415, 1994 (Released:2009-06-30)

参考文献数

43

被引用文献数

1

著者

矢田 恒二

出版者

公益社団法人 精密工学会

雑誌

精密工学会誌 (ISSN:09120289)

巻号頁・発行日

vol.56, no.9, pp.1575-1580, 1990-09-05 (Released:2009-06-30)

参考文献数

16

被引用文献数

1 1

著者

加藤 康司

出版者

公益社団法人 精密工学会

雑誌

精密工学会誌 (ISSN:09120289)

巻号頁・発行日

vol.56, no.9, pp.1602-1606, 1990-09-05 (Released:2009-06-30)

参考文献数

4

被引用文献数

3 6

著者

中川 邦彦 森 一夫

出版者

公益社団法人 精密工学会

雑誌

精密工学会誌 (ISSN:09120289)

巻号頁・発行日

vol.56, no.9, pp.1607-1610, 1990-09-05 (Released:2009-06-30)

参考文献数

3

著者

高橋 道郎 大塚 二郎

出版者

公益社団法人 精密工学会

雑誌

精密工学会誌 (ISSN:09120289)

巻号頁・発行日

vol.56, no.9, pp.1611-1614, 1990-09-05 (Released:2009-06-30)

参考文献数

9

被引用文献数

1 2

著者

町田 尚

出版者

公益社団法人 精密工学会

雑誌

精密工学会誌 (ISSN:09120289)

巻号頁・発行日

vol.56, no.9, pp.1597-1601, 1990-09-05 (Released:2010-02-16)

参考文献数

11

被引用文献数

1

著者

畑 一志

出版者

公益社団法人 精密工学会

雑誌

精密工学会誌 (ISSN:09120289)

巻号頁・発行日

vol.56, no.9, pp.1589-1592, 1990-09-05 (Released:2010-02-16)

参考文献数

15

被引用文献数

1

著者

Shuxiang LI Xin GAO Yancai WEI Gengchao ZHU Chen YANG

出版者

Center for Academic Publications Japan

雑誌

Journal of Nutritional Science and Vitaminology (ISSN:03014800)

巻号頁・発行日

vol.62, no.6, pp.397-401, 2016 (Released:2017-02-16)

参考文献数

26

被引用文献数

22

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Previous studies have identified an association between iron deficiency and thyroid function. We aimed to determine if there is a relationship between iron deficiency and thyroid function during the first trimester of pregnancy. Two thousand five hundred eighty-one pregnant women who presented for the first prenatal care were enrolled and divided into three groups, the mild iron deficiency (MID) group, iron deficiency anemia (IDA) group and normal control (NC) group, according to serum ferritin and hemoglobin levels. The former two groups can be merged into one iron deficiency (ID) group. Thyroid function parameters were compared among the three groups, including free thyroxine (FT4), thyroid stimulating hormone (TSH), total thyroxine (TT4) and thyroid peroxidase antibodies (TPOAb). Moreover, the rates of thyroid dysfunction were also compared. Our results show that pregnant women in the MID and IDA groups have higher TSH and lower FT4 status than those in the NC group (p<0.01), and the difference between the IDA group and MID group is significant (p<0.05). TPOAb in the IDA group is higher than in the MID group and NC group. Meanwhile, the rate of hypothyroidism or subclinical hypothyroidism in the IDA group was significantly higher than in the MID group and NC group (p<0.01). And the positive rate of TPOAb is also higher in the IDA group than MID group and NC group (p<0.05). Iron deficiency is related to thyroid function and could lead to hypothyroidism during early pregnancy, which could be explained by thyroid autoimmunity.