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

KDM1A maintains genome-wide homeostasis of transcriptional enhancers

Transcriptional enhancers enable exquisite spatiotemporal control of gene expression in metazoans. Enrichment of monomethylation of histone H3 lysine 4 (H3K4me1) is a major chromatin signature of transcriptional enhancers. Lysine (K)-specific demethylase 1A (KDM1A, also known as LSD1), an H3K4me2/me1 demethylase, inactivates stem-cell enhancers during the differentiation of mouse embryonic stem cells (mESCs). However, its role in undifferentiated mESCs remains obscure. Here, we show that KDM1A actively maintains the optimal enhancer status in both undifferentiated and lineage-committed cells. KDM1A occupies a majority of enhancers in undifferentiated mESCs. KDM1A levels at enhancers exhibit clear positive correlations with its substrate H3K4me2, H3K27ac, and transcription at enhancers. In Kdm1a-deficient mESCs, a large fraction of these enhancers gains additional H3K4 methylation, which is accompanied by increases in H3K27 acetylation and increased expression of both enhancer RNAs (eRNAs) and target genes. In postmitotic neurons, loss of KDM1A leads to premature activation of neuronal activity-dependent enhancers and genes. Taken together, these results suggest that KDM1A is a versatile regulator of enhancers and acts as a rheostat to maintain optimal enhancer activity by counterbalancing H3K4 methylation at enhancers

Exploration of serum biomarkers in dogs with malignant melanoma receiving anti-PD-L1 therapy and potential of COX-2 inhibition for combination therapy

Immune checkpoint inhibitors (ICIs) such as anti-PD-L1 antibodies are widely used to treat human cancers, and growing evidence suggests that ICIs are promising treatments for canine malignancies. However, only some canine oral malignant melanoma (OMM) cases respond to ICIs. To explore biomarkers predictive of survival in dogs with pulmonary metastatic OMM receiving the anti-PD-L1 antibody c4G12 (n = 27), serum concentrations of prostaglandin E2 (PGE(2)), cytokines, chemokines, and growth factors were measured prior to treatment initiation. Among 12 factors tested, PGE(2), interleukin (IL)-12p40, IL-8, monocyte chemotactic protein-1 (MCP-1), and stem cell factor (SCF) were higher in OMM dogs compared to healthy dogs (n = 8). Further, lower baseline serum PGE(2), MCP-1, and vascular endothelial growth factor (VEGF)-A concentrations as well as higher IL-2, IL-12, and SCF concentrations predicted prolonged overall survival. These observations suggest that PGE(2) confers resistance against anti-PD-L1 therapy through immunosuppression and thus is a candidate target for combination therapy. Indeed, PGE(2) suppressed IL-2 and interferon (IFN)-gamma production by stimulated canine peripheral blood mononuclear cells (PBMCs), while inhibition of PGE(2) biosynthesis using the COX-2 inhibitor meloxicam in combination with c4G12 enhanced Th1 cytokine production by PBMCs. Thus, serum PGE(2) may be predictive of c4G12 treatment response, and concomitant use of COX-2 inhibitors may enhance ICI antitumor efficacy

Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors

Spontaneous tumors are a major cause of death in cats. Treatment of human tumors has progressed dramatically in the past decade, partly due to the success of immunotherapies using immune checkpoint inhibitors, such as anti-programmed death 1 (PD-1) and anti-PD-ligand 1 (PD-L1) antibodies. However, little is known about the PD-1 pathway and its association with tumor disease in cats. This study investigated the applicability of anti-PD-1/PD-L1 therapy in feline tumors. We first determined the complete coding sequence of feline PD-L1 and PD-L2, and found that the deduced amino acid sequences of feline PD-L1/PD-L2 share high sequence identities (66-83%) with orthologs in other mammalian species. We prepared recombinant feline PD-1, PD-L1, and PD-L2 proteins and confirmed receptor-ligand binding between PD-1 and PD-L1/PD-L2 using flow cytometry. Next, we established an anti-feline PD-L1 monoclonal antibody (clone CL1Mab-7) to analyze the expression of PD-L1. Flow cytometry using CL1Mab-7 revealed the cell surface expression of PD-L1 in a feline macrophage (Fcwf-4) and five mammary adenocarcinoma cell lines (FKNp, FMCm, FYMp, FONp, and FONm), and showed that PD-L1 expression was upregulated by interferon-gamma stimulation. Finally, immunohistochemistry using CL1Mab-7 also showed PD-L1 expression in feline squamous cell carcinoma (5/5, 100%), mammary adenocarcinoma (4/5, 80%), fibrosarcoma (5/5, 100%), and renal cell carcinoma (2/2, 100%) tissues. Our results strongly encourage further investigations of the PD-1/PD-L1 pathway as a potential therapeutic target for feline tumors