Chlamydial Infection-Dependent Synthesis of Sphingomyelin as a Novel Anti-Chlamydial Target of Ceramide Mimetic Compounds

The obligate intracellular bacterium Chlamydia trachomatis is the major causative agent of bacterial sexually transmitted diseases worldwide. In infected cells, the ceramide transport protein (CERT) is recruited to inclusions, where C. trachomatis replicates using host-synthesized ceramide. The ceramide is converted to sphingomyelin (SM) by a chlamydial infection-dependent SM synthesis (cidSM-synthesis) pathway, which occurs even in the absence of the SM synthases (SMS)-1 and -2 of host cells. The ceramide mimetic compound (1R,3S)-HPA-12 and the nonmimetic compound E16A, both of which are potent inhibitors of CERT, repressed the proliferation of C. trachomatis in HeLa cells. Unexpectedly, (1R,3R)-HPA-12, a ceramide mimetic compound that lacks CERT inhibitory activity, also exhibited potent anti-chlamydial activity. Using endogenous SMS-knockout mutant HeLa cells, we revealed that (1R,3R)-HPA-12 mildly inhibited cidSM-synthesis. In addition, LC-MS analysis revealed that (1R,3R)-HPA-12 is converted to a phosphocholine-conjugated metabolite in an infection-dependent manner. Imaging analysis with a fluorescent analog of ceramide suggested that cidSM-synthesis occurs in the bacterial bodies and/or inclusions. Collectively, these results suggested that (1R,3R)-HPA-12 exerts its anti-chlamydia activity not only as an inhibitor of cidSM-synthesis, but also via putative toxic effects of its phosphocholine adduct, which is most likely produced by the cidSM-synthesis route

高等特別支援学校（知的障害）と高等学校における交流及び共同学習の取組 : 「 総合的な探究の時間」を中心に

共生社会の実現を目指すには、インクルーシブ教育システムの構築が必要であり、その中でも交流及び共同学習の推進は肝要である。これまでの交流及び共同学習の報告の内、学校間で行う交流及び共同学習においては、高等学校段階の報告はわずかであり、同一行政区が設置する学校間で行事や部活動を通して実践していることが多い。本稿は、県立・市立という行政枠を超えた高等学校段階における「総合的な探究の時間」の交流及び共同学習の３年間にわたる実践をもとに、両校の教職員の変化、両校の生徒の変化等を検討したものである。継続的な取組により、学校間の抵抗感が軽減され、生徒同士のトラブル対応にもすぐに相互の教員が連絡を取り合って動く等、教員の連携が強まり、生徒同士も知り合い、理解しあう様子が見られるなど、学校間交流の効果が見られた。「総合的な探究の時間」の特質が交流及び共同学習として取り組みやすいことが考えられ、交流及び共同学習を継続させる仕組みつくりを行うには、双方の学校の教育課程に位置付け、実践後の評価と改善を意図的に行うことの重要性が考えられた。Building an inclusive education system is necessary to realize a symbiotic society, and the promotion of exchange and joint learning is one of the key elements of this system. Until now, there are only a few reports on “Exchange and Joint Learning” at the high school level, and most of them are conducted through events and club activities among schools established in the same school district. This study examined attitudinal changes in the teachers and students of the two schools based on three years of exchange and joint learning practice during the “Period for Inquiry-Based Cross-Disciplinary Study” at the upper secondary school level, transcending the administrative boundaries of prefectural and municipal governments. Through continuous efforts, the sense of resistance between the two schools was reduced, teachers’ cooperation was strengthened, and students got to know and understand each other. The characteristics of the “Period for Inquiry-Based Cross-Disciplinary Study” may be a reason for facilitating exchange and collaborative learning. To sustain exchange and collaborative learning, it is considered important to place it in the curricula of both schools and to evaluate and improve it after implementation intentionally

WRN participates in translesion synthesis pathway through interaction with NBS1.

Werner syndrome (WS), caused by mutation of the WRN gene, is an autosomal recessive disorder associated with premature aging and predisposition to cancer. WRN belongs to the RecQ DNA helicase family, members of which play a role in maintaining genomic stability. Here, we demonstrate that WRN rapidly forms discrete nuclear foci in an NBS1-dependent manner following DNA damage. NBS1 physically interacts with WRN through its FHA domain, which interaction is important for the phosphorylation of WRN. WRN subsequently forms DNA damage-dependent foci during the S phase, but not in the G1 phase. WS cells exhibit an increase in spontaneous focus formation of poleta and Rad18, which are important for translesion synthesis (TLS). WRN also interacts with PCNA in the absence of DNA damage, but DNA damage induces the dissociation of PCNA from WRN, leading to the ubiquitination of PCNA, which is essential for TLS. This dissociation correlates with ATM/NBS1-dependent degradation of WRN. Moreover, WS cells show constitutive ubiquitination of PCNA and interaction between PCNA and Rad18 E3 ligase in the absence of DNA damage. Taken together, these results indicate that WRN participates in the TLS pathway to prevent genomic instability in an ATM/NBS1-dependent manner

Age-related decrease of miRNA-92a levels in human CD8+ T-cells correlates with a reduction of naïve T lymphocytes

MicroRNA (miR)-17-92a expression plays a crucial role in lymphocyte ontogeny. We therefore set out to determine miR-92a expression levels in peripheral blood lymphocytes from healthy subjects to ascertain any association between these levels and ageing. We found a positive correlation between the miR-92a expression level and the percentages of RO-CD8+CD27+ (P = 0.0046) and CD3+CD8+CD62L+ (P = 0.0011). This suggests that the majority of miR-92a of CD8+ T cells is derived from naïve cells, and the miR-92a expression level in CD8+ T cells declines progressively with age. These results indicate that the age-related attrition of naïve T cells is linked to a reduction of miR-92a in human T -lymphocytes. Therefore, we should careful attention when evaluating human miRNA levels in T lymphocytes to use normal control values

ヒボゴワシャ ニホンゴキョウシ ノ キャリア ケイセイ カテイ ト カダイ -マレーシア ヨビ キョウイク キカン AAJ ヲ レイ ニ-

マラヤ大学予備教育部日本留学コースでは、1982年のコース開設当初から国際交流基金より継続的に派遣されてきた日本語教師が、現地のマレーシア人教師とともに予備教育に従事してきた。発足当初は1名であったマレーシア人教師も今では12名に増え、教授活動だけでなく、新任教師に対する研修・指導のほかに自身の研究業績が求められるようになり、マレーシアの日本語教育の将来を担う人材となった。本研究では当機関で日本語教育に携わってきたマレーシア人日本語教師にインタビュー調査を行ない、彼らのキャリア形成過程を明らかにするとともに今後のキャリア形成上の課題と展望について考察した。今後の課題としてはマレーシア国内において次世代の日本語教師を養成すること、マレーシア人日本語教師が国内で日本語に関する研究を行ない、発表できる環境を整えることなどが挙げられる。これらの実現に向けて今後のマレーシアの日本語教育に対する日本側の支援について提言する。The Japan Foundation has been sending Japanese-Language Specialists to the Special Preparatory Program for Entry into Japanese Universities at the University of Malaya (Ambang Asuhan Jepun) since the program was launched in 1982. In recent years, the program has seen an increase in Malaysian teachers working with teachers from Japan, and their new responsibilities not only as language teachers but also as trainers of new teachers and as researchers, presumably assuming a future leadership role in Japanese language education in Malaysia. The present study investigates the career development process of these teachers through interviews and discusses issues and future prospects for their career advancement. The study reveals the necessity of training Japanese language teachers in Malaysia as well as of providing Malaysian teachers with more opportunities to conduct and present research related to Japanese language. Suggestions on how Japan might support the Japanese language teaching in Malaysia are given

Factors related to employment in childhood cancer survivors in Japan: A preliminary study

PurposePrevious research has revealed vocational and academic difficulties in childhood cancer survivors, and explored impact of survivors' medical history and physical function on vocational and academic status. However, we often encounter survivors with similar diagnoses and late effects but different academic or employment statuses. This raises the question of what affects academic attainment and employment other than treatment or late effects. This study aimed to explore factors associated with childhood cancer survivors' employment status and academic achievement.MethodsComprehensive health check-up and questionnaire survey were conducted for 69 survivors who were over the age of 18 and participated in St. Luke's Lifetime cohort study. We obtained survivors' biological function using comprehensive health check-up, neurocognitive states, quality of life, transition readiness, and family function. We conducted univariate analysis (Mann–Whitney U tests or chi-square tests) to compare the differences between the regular workers/students and non-regular workers/unemployed groups. The variables with p-values <0.1 were used as independent variables multivariate logistic regression to explore predictors of employment status and academic attainment.ResultsResult of the univariate analysis, intelligence quotient, SF-8 PCS, transition readiness, family function were used for multivariate logistic regression as independent variables. The stepwise likelihood method was conducted; intelligence quotient (odds ratio [OR] = 1.100; 95% confidence interval [CI] 1.015–1.193; p = 0.021), transition readiness (OR = 0.612; 95% CI 0.396–0.974; p = 0.038), and family function (OR = 2.337; 95% CI 1.175–4.645; p = 0.015) were found to be associated with survivors' regular workers/students in the final regression model.ConclusionLong-term follow-up of pediatric cancer survivors requires the provision of total care, which supports physical, psychological, and social functions to improve health, readiness for transition to self-management, and family functioning

ことばの遅れを示す幼児における状況絵の説明能力の検討

This study examined the narrative skills of seven preschoolers with language delay. Their narrative skills were assessed by speech samples obtained through a picture stimulus task. First, they were presented with a single picture showing a squabble over a swing (Task 1). In Task 1, because the picture contained so much information, the children became confused. We then showed three sequential pictures, illustrating the same theme, which included only essential information (Task 2). In Task 2, the children understood the contents of the pictures and could explain the situation with appropriate vocabulary and complex syntax. In other words, if the information is properly arranged in the picture stimulus, preschoolers with language delay can show potential syntactic ability. These findings demonstrate the importance of proper arrangement of the information in the picture stimulus used in language evaluation

ことばの遅れを示す幼児における説明能力の検討 : 逆順方略課題による

We showed picture stimulus to preschoolers with language delay and obtained verbal output samples to study their narrative skilles. ThePicture stimulus were presented in a result-to-cause sequence. The children were unable to achieve the task of backward reasoning.Additional use of thought bubbles enabled them to explain pictures, demonstrationg that guessing how the characters in the pictures felt helped them explain non-describeb scenes. This paper reports that the use of thought bubles are effective in improving narrative skills

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A study of social anxiety among Japanese working adults

The major purpose of this study was to examine the association between social anxiety and self-construal among Japanese adults including an investigation of gender and age differences vis-Ã -vis social anxiety. One hundred thirty-six Japanese office workers (male = 84, female = 52) working in the Philippines and in Japan, ranging in age from 20 to 54 years participated in the study. The researcher administrated the Fear of Negative Evaluation Scale and the Social Avoidance and Distress Scale to measure the level of social anxiety. The Self-Construal Scale was employed to assess independent and interdependent tendency of the self. Correlation, t-test and regression statistics were applied to analyze the data. Of the respondents, ten (male = 5, female = 5) participated in the semi-structured interviews conducted to obtain in-depth information about actual experiences of social anxiety. The results revealed that the independent self-construal was significantly negatively correlated with both social anxiety scales. The interdependent self-construal and gender did not have a significant influence on social anxiety. Age was significantly negatively correlated with the fear of negative evaluation. Independent self-construal was the best predictor of social anxiety compared to the other variables considered in the study. The findings of the interviews supported the results of the quantitative research. The study implied that independence and individuality lower the level of social anxiety, and that the individuals become less socially anxious as they grow older