Oxidative Modification to Cysteine Sulfonic Acid of Cys111 in Human Copper-Zinc Superoxide Dismutase

Copper-zinc superoxide dismutase (SOD1) plays a protective role against oxidative stress. On the other hand, recent studies suggest that SOD1 itself is a major target of oxidative damage and has its own pathogenicity in various neurodegenerative diseases, including familial amyotrophic lateral sclerosis. Only human and great ape SOD1s among mammals have the highly reactive free cysteine residue, Cys111, at the surface of the SOD1 molecule. The purpose of this study was to investigate the role of Cys111 in the oxidative damage of the SOD1 protein, by comparing the oxidative susceptibility of recombinant human SOD1 modified with 2-mercaptoethanol at Cys111 (2-ME-SOD1) to wild-type SOD1. Wild-type SOD1 was more sensitive to oxidation by hydrogen peroxide-generating fragments, oligomers, and charge isomers compared with 2-ME-SOD1. Moreover, wild-type SOD1, but not 2-ME-SOD1, generated an upper shifted band in reducing SDS-PAGE even by air oxidation. Using mass spectrometry and limited proteolysis, this upper band was identified as an oxidized subunit of SOD1; the sulfhydryl group (Cys-SH) of Cys111 was selectively oxidized to cysteine sulfinic acid (Cys-SO2H) and to cysteine sulfonic acid (Cys-SO3H). The antibody raised against a synthesized peptide containing Cys111-SO3H reacted with only the Cys111-peroxidized SOD1 by Western blot analysis and labeled Lewy bodylike hyaline inclusions and vacuole rims in the spinal cord of human SOD1-mutated amyotrophic lateral sclerosis mice by immunohistochemical analysis. These results suggest that Cys111 is a primary target for oxidative modification and plays an important role in oxidative damage to human SOD1, including familial amyotrophic lateral sclerosis mutants.This work was supported by Grants-in-aid for Scientific Research 17500242 and 19500313; a Hitech Research Center grant and the 21st Century Centers of Excellence program from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and in part by a Grant for the Research Group on Development of Novel Therapeutics for ALS from the Ministry of Health, Labor and Welfare of Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact

The novel functional nucleic acid iRed effectively regulates target genes following cytoplasmic delivery by faint electric treatment

An intelligent shRNA expression device (iRed) contains the minimum essential components needed for shRNA production in cells, and could be a novel tool to regulate target genes. However, general delivery carriers consisting of cationic polymers/lipids could impede function of a newly generated shRNA via electrostatic interaction in the cytoplasm. Recently, we found that faint electric treatment (fET) of cells enhanced delivery of siRNA and functional nucleic acids into the cytoplasm in the absence of delivery carriers. Here, we examined fET of cells stably expressing luciferase in the presence of iRed encoding anti-luciferase shRNA. Transfection of lipofectamine 2000 (LFN)/iRed lipoplexes showed an RNAi effect, but fET-mediated iRed transfection did not, likely because of the endosomal localization of iRed after delivery. However, fET in the presence of lysosomotropic agent chloroquine significantly improved the RNAi effect of iRed/fET to levels that were higher than those for the LFN/iRed lipoplexes. Furthermore, the amount of lipid droplets in adipocytes significantly decreased following fET with iRed against resistin in the presence of chloroquine. Thus, iRed could be a useful tool to regulate target genes following fET-mediated cytoplasmic delivery with endosomal escape devices

The New School Absentees Reporting System for Pandemic Influenza A/H1N1 2009 Infection in Japan

Objective: To evaluate the new Japanese School Absentees Reporting System for Infectious Disease (SARSID) for pandemic influenza A/H1N1 2009 infection in comparison with the National epidemiological Surveillance of Infectious Disease (NESID). Methods:We used data of 53,223 students (97.7%) in Takamatsu city Japan. Data regarding school absentees in SARSID was compared with that in NESID from Oct 13, 2009 to Jan 12, 2010. Results: Similar trends were observed both in SARSID and NESID. However, the epidemic trend for influenza in SARSID was thought to be more sensitive than that in NESID. Conclusion: The epidemic trend for influenza among school-aged children could be easily and rapidly assessed by SARSID compared to NESID. SARSID might be useful for detecting the epidemic trend of influenza

住民による高齢者サロン運営の課題と対策

一般高齢者の介護予防推進事業である高齢者サロン運営の課題と対策を検討する目的で島根県出雲市C地区の高齢者サロンに参加して実態把握をするとともに、サロンの世話役・福祉委員・参加者等に実施したインタビュー結果をサロン活動の継続の困難さに視点を当て分析した。課題は①独居高齢者等の不参加②参加意欲維持の困難さ③働き盛り男性福祉委員の活動の困難性④世話役の高齢化と人材不足による活動の困難性⑤企画内容の工夫の困難性⑥活動記録等の保存と活用の不徹底⑦社会資源等の情報伝達と周知不足⑧予算確保の困難性・助成金の使途制限による使用の困難性⑨実施場所と回数の不足⑩実施場所の環境整備不足であった。対策として社会福祉協議会、自治協会・保健師などがサロン運営の課題を共有する機会を持ち、サロンを運営する世話役や福祉委員への情報提供や必要な支援することが重要である。また、高齢者が主体的に参加できるよう協力を求めながら実施していく必要がある

片桐洋一教授所蔵 古今伝授書解題

片桐洋一教授古稀記念特

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2010: General view of the pathogens\u27 antibacterial susceptibility

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, was conducted by Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases and Japanese Society for Clinical Microbiology in 2010.The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period from January and April 2010 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical and Laboratory Standard Institutes using maximum 45 antibacterial agents.Susceptibility testing was evaluable with 954 strains (206 Staphylococcus aureus, 189 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 182 Haemophilus influenzae, 74 Moraxella catarrhalis, 139 Klebsiella pneumoniae and 160 Pseudomonas aeruginosa). Ratio of methicillin-resistant S.aureus was as high as 50.5%, and those of penicillin-intermediate and -resistant S.pneumoniae were 1.1% and 0.0%, respectively. Among H.influenzae, 17.6% of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant, 33.5% to be β-lactamase-non-producing ABPC-resistant and 11.0% to be β-lactamase-producing ABPC-resistant strains. Extended spectrum β-lactamase-producing K.pneumoniae and multi-drug resistant P.aeruginosa with metallo β-lactamase were 2.9% and 0.6%, respectively.Continuous national surveillance of antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis

Corpus Construction for Historical Newspapers: A Case Study on Public Meeting Corpus Construction using OCR Error Correction

Large text corpora are indispensable for natural language processing. However, in various fields such as literature and humanities, many documents to be studied are only scanned to images, but not converted to text data. Optical character recognition (OCR) is a technology to convert scanned document images into text data. However, OCR often misrecognizes characters due to the low quality of the scanned document images, which is a crucial factor that degrades the quality of constructed text corpora. This paper works on corpus construction for historical newspapers. We present a corpus construction method based on a pipeline of image processing, OCR, and filtering. To improve the quality, we further propose to integrate OCR error correction. To this end, we manually construct an OCR error correction dataset in the historical newspaper domain, propose methods to improve a neural OCR correction model and compare various OCR error correction models. We evaluate our corpus construction method on the accuracy of extracting articles of a specific topic to construct a historical newspaper corpus. As a result, our method improves the article extraction F score by 1.7% via OCR error correction comparing to previous work. This verifies the effectiveness of OCR error correction for corpus construction

The novel functional nucleic acid iRed effectively regulates target genes following cytoplasmic delivery by faint electric treatment

An intelligent shRNA expression device (iRed) contains the minimum essential components needed for shRNA production in cells, and could be a novel tool to regulate target genes. However, general delivery carriers consisting of cationic polymers/lipids could impede function of a newly generated shRNA via electrostatic interaction in the cytoplasm. Recently, we found that faint electric treatment (fET) of cells enhanced delivery of siRNA and functional nucleic acids into the cytoplasm in the absence of delivery carriers. Here, we examined fET of cells stably expressing luciferase in the presence of iRed encoding anti-luciferase shRNA. Transfection of lipofectamine 2000 (LFN)/iRed lipoplexes showed an RNAi effect, but fET-mediated iRed transfection did not, likely because of the endosomal localization of iRed after delivery. However, fET in the presence of lysosomotropic agent chloroquine significantly improved the RNAi effect of iRed/fET to levels that were higher than those for the LFN/iRed lipoplexes. Furthermore, the amount of lipid droplets in adipocytes significantly decreased following fET with iRed against resistin in the presence of chloroquine. Thus, iRed could be a useful tool to regulate target genes following fET-mediated cytoplasmic delivery with endosomal escape devices

Information Extraction from Public Meeting Articles

Public meeting articles are the key to understanding the history of public opinion and public sphere in Australia. Information extraction from public meeting articles can obtain new insights into Australian history. In this paper, we create an information extraction dataset in the public meeting domain. We manually annotate the date and time, place, purpose, people who requested the meeting, people who convened the meeting, and people who were convened of 1258 public meeting articles. We further present an information extraction system, which formulates information extraction from public meeting articles as a machine reading comprehension task. Experiments indicate that our system can achieve an F1 score of 74.98% for information extraction from public meeting articles