〈報告〉中上級日本語学習者のための作文ガイドブックの開発

本稿では、中上級学習者のアカデミック・ジャパニーズのための作文学習を支援する作文ガイドブック作成に至る過程を概説し、試作した作文ガイドブックについて報告する。作文学習の際、日本語レベルを超えて共有すべき学習項目を特定し、レベル縦断の内容として各レベルの学習者が必要に応じて参照できれば、より学習効果が上がると考える。そこで、大学の補講日本語コースの中上級作文クラスにおいて、コースシラバス作成、レベルチェック作文分析の結果を踏まえて、作文ガイドブックの作成を行った。複数のレベルで誤用が見られる文体と文脈に関わる文法的な表現の中で学習項目として、文体、引用、接続詞・接続助詞、疑問文、文末表現、「る・た・ている」テンス・アスペクトという６項目を取り上げ、パワーポイント資料を作成した。共有できる学習資源として、作文授業を担当する教師や作文を書く学習者が利用しやすい内容や形式にして公開していくことが重要である。This paper outlines the process leading up to the preparation of a composition guidebook to support intermediate-advanced level learners learning composition for academic Japanese, and reports on the guidebook development. We hypothesize that during the composition learning process, learning will be more effective if learners, regardless of their levels, can refer to a set of essential learning items. Therefore, we prepared a composition guidebook based on the results of course syllabi and level check composition analysis in the intermediate-advanced composition classes of the supplementary Japanese language course of our university. At multiple learner levels, we observed errors related to style and context in grammar expression. Based on the errors, we selected six learning items, namely writing style, quotation, conjunction and conjunctive particles, interrogative sentences, sentence-ending expressions, and tense and aspect. We then created PowerPoint materials. As a learning resource that can be shared, it is important to make it accessible to both the teachers who are in charge of writing composition and to the learners who write compositions, in an easy-to-use content and format

Concomitant administration of radiation with eribulin improves the survival of mice harboring intracerebral glioblastoma

Glioblastoma is the most common and devastating type of malignant brain tumor. We recently found that eribulin suppresses glioma growth in vitro and in vivo and that eribulin is efficiently transferred into mouse brain tumors at a high concentration. Eribulin is a non‐taxane microtubule inhibitor approved for breast cancer and liposarcoma. Cells arrested in M‐phase by chemotherapeutic agents such as microtubule inhibitors are highly sensitive to radiation‐induced DNA damage. Several recent case reports have demonstrated the clinical benefits of eribulin combined with radiation therapy for metastatic brain tumors. In this study, we investigated the efficacy of a combined eribulin and radiation treatment on human glioblastoma cells. The glioblastoma cell lines U87MG, U251MG and U118MG, and SJ28 cells, a patient‐derived sphere culture cell line, were used to determine the radiosensitizing effect of eribulin using western blotting, flow cytometry and clonogenic assay. Subcutaneous and intracerebral glioma xenografts were generated in mice to assess the efficacy of the combined treatment. The combination of eribulin and radiation enhanced DNA damage in vitro. The clonogenic assay of U87MG demonstrated the radiosensitizing effect of eribulin. The concomitant eribulin and radiation treatment significantly prolonged the survival of mice harboring intracerebral glioma xenografts compared with eribulin or radiation alone (P < .0001). In addition, maintenance administration of eribulin after the concomitant treatment further controlled brain tumor growth. Aberrant microvasculature was decreased in these tumors. Concomitant treatment with eribulin and radiation followed by maintenance administration of eribulin may serve as a novel therapeutic strategy for glioblastomas

Combining poly-arginine with the hydrophobic counter-anion 4-(1-pyrenyl)-butyric acid for protein transduction in transdermal delivery

Topical therapy is the most favored form of treatment for whitening against hyperpigmentation and sunburn because it lends itself to self-administration, patient compliance, and absence of systemic adverse effects. However, transdermal delivery of hydrophilic chemicals is difficult. The main purpose of this study is to develop a delivering system of hydrophilic drugs and proteins across the skin. Hydroquinone (HQ), a well-known tyrosinase inhibitor and antimelanogenesis compound, and enhanced green fluorescent protein (EGFP) were fused with eleven poly-arginine (11R). Both HQ-11R and EGFP-11R were efficiently delivered in B16 cells, a mouse melanoma cell line. HQ-11R was as effective as HQ alone at inhibiting melanin synthesis in B16 cells. EGFP-11R was efficiently delivered into cells of the epidermis with 4-(1-pyrenyl)-butyric acid (PB), a counteranion bearing an aromatic hydrophobic moiety, in vivo, but EGFP alone or EGFP-11R without PB was not. Finally, topical application of HQ-11R with PB significantly inhibited UV irradiation-induced pigmentation in guinea pigs compared with HQ alone. These results suggest that topical therapy using poly-arginine in combination with PB is useful for the delivery of hydrophilic drugs and proteins by the transdermal route

Transcriptional Activation of Low-Density Lipoprotein Receptor Gene by DJ-1 and Effect of DJ-1 on Cholesterol Homeostasis

DJ-1 is a novel oncogene and also causative gene for familial Parkinson’s disease park7. DJ-1 has multiple functions that include transcriptional regulation, anti-oxidative reaction and chaperone and mitochondrial regulation. For transcriptional regulation, DJ-1 acts as a coactivator that binds to various transcription factors, resulting in stimulation or repression of the expression of their target genes. In this study, we found the low-density lipoprotein receptor (LDLR) gene is a transcriptional target gene for DJ-1. Reduced expression of LDLR mRNA and protein was observed in DJ-1-knockdown cells and DJ-1-knockout mice and this occurred at the transcription level. Reporter gene assays using various deletion and point mutations of the LDLR promoter showed that DJ-1 stimulated promoter activity by binding to the sterol regulatory element (SRE) with sterol regulatory element binding protein (SREBP) and that stimulating activity of DJ-1 toward LDLR promoter activity was enhanced by oxidation of DJ-1. Chromatin immunoprecipitation, gel-mobility shift and co-immunoprecipitation assays showed that DJ-1 made a complex with SREBP on the SRE. Furthermore, it was found that serum LDL cholesterol level was increased in DJ-1-knockout male, but not female, mice and that the increased serum LDL cholesterol level in DJ-1-knockout male mice was cancelled by administration with estrogen, suggesting that estrogen compensates the increased level of serum LDL cholesterol in DJ-1-knockout female mice. This is the first report that DJ-1 participates in metabolism of fatty acid synthesis through transcriptional regulation of the LDLR gene

Stimulation of vesicular monoamine transporter 2 activity by DJ-1 in SH-SY5Y cells

Loss-of-functional mutation in the DJ-1 gene causes a subset of familial Parkinson's disease. The mechanism underlying DJ-1-related selective vulnerability in the dopaminergic pathway is, however, not known. Dopamine is synthesized by two enzymes and then packed into synaptic vesicles by vesicular monoamine transporter 2 (VMAT2). In this study, we found that knockdown of DJ-1 expression reduced the levels of mRNA and protein of VMAT2, resulting in reduced VMAT2 activity. Co-immunoprecipitation and pull-down experiments revealed that DJ-1 directly bound to VMAT2, and DJ-1 was co-localized with VMAT2 in cells. Furthermore, ectopic expression of wild-type DJ-1, but not that of L166P, M261 and C106S mutants of DJ-1, increased mRNA and protein levels of VMAT2 and VMAT2 activity. Since VMAT2 and a portion of DJ-1 are localized in the synaptic membrane, these results suggest that DJ-1, but not pathogenically mutated DJ-1, stimulates VMAT2 activity in the synapse by transactivation of the VMAT gene and by direct binding to VMAT2 and that cysteine 106 is necessary for the stimulating activity of DJ-1 toward VMAT2

Future Therapies of Wet Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population, and the prevalence of the disease increases exponentially with every decade after the age of 50 years. While VEGF inhibitors are promising drugs for treating patients with ocular neovascularization, there are limitations to their potential for improving vision in AMD patients. Thus, future therapies are required to have the potential to improve visual outcomes. This paper will summarize the future strategies and therapeutic targets that are aimed at enhancing the efficacy and duration of effect of antiangiogenic strategies