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Inhibitory receptor paired Ig-like receptor B is exploited by Staphylococcus aureus for virulence.
Nakayama, Masafumi,Kurokawa, Kenji,Nakamura, Kyohei,Lee, Bok Luel,Sekimizu, Kazuhisa,Kubagawa, Hiromi,Hiramatsu, Keiichi,Yagita, Hideo,Okumura, Ko,Takai, Toshiyuki,Underhill, David M,Aderem, Alan,Ogas American Association of Immunologists 2012 Journal of Immunology Vol. No.
<P>The innate immune system has developed to acquire a wide variety of pattern-recognition receptors (PRRs) to identify potential pathogens, whereas pathogens have also developed to escape host innate immune responses. ITIM-bearing receptors are attractive targets for pathogens to attenuate immune responses against them; however, the in vivo role of the inhibitory PRRs in host-bacteria interactions remains unknown. We demonstrate in this article that Staphylococcus aureus, a major Gram-positive bacteria, exploits inhibitory PRR paired Ig-like receptor (PIR)-B on macrophages to suppress ERK1/2 and inflammasome activation, and subsequent IL-6 and IL-1β secretion. Consequently, Pirb(-/-) mice infected with S. aureus showed enhanced inflammation and more effective bacterial clearance, resulting in resistance to the sepsis. Screening of S. aureus mutants identified lipoteichoic acid (LTA) as an essential bacterial cell wall component required for binding to PIR-B and modulating inflammatory responses. In vivo, however, an LTA-deficient S. aureus mutant was highly virulent and poorly recognized by macrophages in both wild-type and Pirb(-/-) mice, demonstrating that LTA recognition by PRRs other than PIR-B mediates effective bacterial elimination. These results provide direct evidence that bacteria exploit the inhibitory receptor for virulence, and host immune system counterbalances the infection.</P>
Kurokawa, Kenji,Ryu, Kyoung-Hwa,Ichikawa, Rie,Masuda, Akiko,Kim, Min-Su,Lee, Hanna,Chae, Jun-Ho,Shimizu, Takashi,Saitoh, Tatsuya,Kuwano, Koichi,Akira, Shizuo,Dohmae, Naoshi,Nakayama, Hiroshi,Lee, Bok American Society for Biochemistry and Molecular Bi 2012 The Journal of biological chemistry Vol.287 No.16
Kurokawa, Kenji,Lee, Hanna,Roh, Kyung-Baeg,Asanuma, Miwako,Kim, Young Sook,Nakayama, Hiroshi,Shiratsuchi, Akiko,Choi, Youngnim,Takeuchi, Osamu,Kang, Hee Jung,Dohmae, Naoshi,Nakanishi, Yoshinobu,Akira, American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.13
<P>Some synthetic lipopeptides, in addition to native lipoproteins derived from both Gram-negative bacteria and mycoplasmas, are known to activate TLR2 (Toll-like receptor 2). However, the native lipoproteins inherent to Gram-positive bacteria, which function as TLR2 ligands, have not been characterized. Here, we have purified a native lipoprotein to homogeneity from Staphylococcus aureus to study as a native TLR2 ligand. The purified 33-kDa lipoprotein was capable of stimulating TLR2 and was identified as a triacylated SitC lipoprotein, which belongs to a family of ATP binding cluster (ABC) transporter substrate-binding proteins. Analyses of the SitC-mediated production of cytokine using mouse peritoneal macrophages revealed that the SitC protein (3 nm) induced the production of tumor necrosis factor-alpha and interleukin-6. Moreover, analysis of knock-out mice showed that SitC required TLR2 and MyD88, but not TLR1 or TLR6, for the induction of cytokines. In addition to the S. aureus SitC lipoprotein, we purified two other native ABC transporter substrate-binding lipoproteins from Bacillus subtilis and Micrococcus luteus, which were both shown to stimulate TLR2. These results demonstrate that S. aureus SitC lipoprotein is triacylated and that the ABC transporter substrate-binding lipoproteins of Gram-positive bacteria function as native ligands for TLR2.</P>
Kashiwao, Tomoaki,Nakayama, Koichi,Ando, Shin,Ikeda, Kenji,Lee, Moonyong,Bahadori, Alireza Elsevier 2017 Applied soft computing Vol.56 No.-
<P>In this study, we develop and test a local rainfall (precipitation) prediction system based on artificial neural networks (ANNs). Our system can automatically obtain meteorological data used for rainfall prediction from the Internet. Meteorological data from equipment installed at a local point is also shared among users in our system. The final goal of the study was the practical use of 'big data' on the Internet as well as the sharing of data among users for accurate rainfall prediction. We predicted local rainfall in regions of Japan using data from the Japan Meteorological Agency (JMA). As neural network (NN) models for the system, we used a multi-layer perceptron (MLP) with a hybrid algorithm composed of back-propagation (BP) and random optimization (RO) methods, and radial basis function network (RBFN) with a least squares method (LSM), and compared the prediction performance of the two models. Precipitation (total amount of rainfall above 0.5 mm between 12: 00 and 24: 00 JST (Japan standard time)) at Matsuyama, Sapporo, and Naha in 2012 was predicted by NNs using meteorological data for each city from 2011. The volume of precipitation was also predicted (total amount above 1.0 mm between 17: 00 and 24: 00 JST) at 16 points in Japan and compared with predictions by the JMA in order to verify the universality of the proposed system. The experimental results showed that precipitation in Japan can be predicted by the proposed method, and that the prediction performance of the MLP model was superior to that of the RBFN model for the rainfall prediction problem. However, the results were not better than those generated by the JMA. Finally, heavy rainfall (above 10 mm/h) in summer (Jun.-Sep.) afternoons (12: 00-24: 00 JST) in Tokyo in 2011 and 2012 was predicted using data for Tokyo between 2000 and 2010. The results showed that the volume of precipitation could be accurately predicted and the caching rate of heavy rainfall was high. This suggests that the proposed system can predict unexpected local heavy rainfalls as 'guerrilla rainstorms.' (C) 2017 Elsevier B.V. All rights reserved.</P>
Structural evidence of <b>α</b>‐aminoacylated lipoproteins of <i>Staphylococcus aureus</i>
Asanuma, Miwako,Kurokawa, Kenji,Ichikawa, Rie,Ryu, Kyoung‐,Hwa,Chae, Jun‐,Ho,Dohmae, Naoshi,Lee, Bok Luel,Nakayama, Hiroshi Blackwell Publishing Ltd 2011 FEBS JOURNAL Vol.278 No.5
<P>Bacterial lipoproteins are known to be diacylated or triacylated and activate mammalian immune cells via Toll‐like receptor 2/6 or 2/1 heterodimer. Because the genomes of low G+C content Gram‐positive bacteria, such as <I>Staphylococcus aureus</I>, do not contain <I>Escherichia coli</I>‐type apolipoprotein <I>N</I>‐acyltransferase, an enzyme converting diacylated lipoproteins into triacylated forms, it has been widely believed that native lipoproteins of <I>S. aureus</I> are diacylated. However, we recently demonstrated that one lipoprotein SitC purified from <I>S. aureus</I> RN4220 strain was triacylated. Almost simultaneously, another group reported that another lipoprotein SA2202 purified from <I>S. aureus</I> SA113 strain was diacylated. The determination of exact lipidated structures of <I>S. aureus</I> lipoproteins is thus crucial for elucidating the molecular basis of host–microorganism interactions. Toward this purpose, we intensively used MS‐based analyses. Here, we demonstrate that SitC lipoprotein of <I>S. aureus</I> RN4220 strain has two lipoprotein lipase‐labile <I>O</I>‐esterified fatty acids and one lipoprotein lipase‐resistant fatty acid. Further MS/MS analysis of the lipoprotein lipase digest revealed that the lipoprotein lipase‐resistant fatty acid was acylated to α‐amino group of the N‐terminal cysteine residue of SitC. Triacylated forms of SitC with various length fatty acids were also confirmed in cell lysate of the RN4220 and Triton X‐114 phase in three other <I>S. aureus</I> strains, including SA113 strain and one <I>Staphylococcus epidermidis</I> strain. Moreover, four other major lipoproteins including SA2202 in <I>S. aureus</I> strains were identified as <I>N</I>‐acylated. These results strongly suggest that lipoproteins of <I>S. aureus</I> are mainly in the <I>N</I>‐acylated triacyl form.</P>
Yuichi Onishi,Shinichi Nakayama,Shinsaku Watanabe,Souichirou Kaneshige,Hajime Monzen,Kenji Matsumoto,Naoya Shintani,Takeshi Kamomae 한국물리학회 2015 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.67 No.1
We constructed seven intensity-modulated radiation therapy (IMRT) treatment plans for prostate cancer (49 irradiation fields which contained seven randomly-sampled patients and seven fields) and evaluated the dose distributions by using a radiochromic film (EBT3 film) and a 2D detector. We superposed the calculated dose distribution of the IMRT treatment plan on EBT3 film and the 2D detector results and then compared those with the -analysis pass rate. The relative positions of the beam and the detector were varied; the results of the analysis of the superior-inferior (SI) direction potentially differed, depending on the detector position, under an irradiation beam with the same fluence map. The detector was moved over a range of ±8 mm in the SI direction in 1-mm step increments, measurement were made at each position, and the results were analyzed. The -analysis compared the dose distributions from EBT3 film and the radiation treatment planning system (RTPS) for each patient and field; the pass rate with the -analysis from 98 to 100% was 2.04%. When we compared the dose distributions of the 2D detector and the RTPS, the pass rate from 98 to 100% was 63.2%. The mean values for the -analysis pass rates for EBT3 film and the 2D detector were 94.2 and 97.6%, respectively. Volume averaging of the data indicated a mean pass rate and standard deviation of 98.6 and 0.91%, respectively, and a pass rate of more than 96% for all positions. A 2D detector can, therefore, be used as an alternative apparatus for IMRT dose verification.