MicroRNA-140 mediates RB tumor suppressor function to control stem cell-like activity through interleukin-6

We established an in vitro cell culture system to determine novel activities of the retinoblastoma (Rb) protein during tumor progression. Rb depletion in p53-null mouse-derived soft tissue sarcoma cells induced a spherogenic phenotype. Cells retrieved from Rb-depleted spheres exhibited slower proliferation and less efficient BrdU incorporation, however, much higher spherogenic activity and aggressive behavior. We discovered six miRNAs, including mmu-miR-18a, -25, -29b, -140, -337, and -1839, whose expression levels correlated tightly with the Rb status and spherogenic activity. Among these, mmu-miR-140 appeared to be positively controlled by Rb and to antagonize the effect of Rb depletion on spherogenesis and tumorigenesis. Furthermore, among genes potentially targeted by mmu-miR-140, Il-6 was upregulated by Rb depletion and downregulated by mmu-mir-140 overexpression. Altogether, we demonstrate the possibility that mmu-mir-140 mediates the Rb function to downregulate Il-6 by targeting its 3\u27-untranslated region. Finally, we detected the same relationship among RB, hsa-miR-140 and IL-6 in a human breast cancer cell line MCF-7. Because IL-6 is a critical modulator of malignant features of cancer cells and the RB pathway is impaired in the majority of cancers, hsa-miR-140 might be a promising therapeutic tool that disrupts linkage between tumor suppressor inactivation and pro-inflammatory cytokine response.Supplementary Table1 and Supplementary Table2: We offer the table data with an Excel fil

現代日本語における形容詞の連用用法 : 外面性／内面性に着目して

博士（学術）12613甲第968号一橋大

The Sun is always Shining in the Sky - Observing the Sun by Means of a Remote Telescope

Tonan High School and Misato Observatory have held an Internet course andd manipulated a remote telescope since February 1997. We have attempted to use the Internet for education. The Misato Observatory developed a remote control telescope system using the CGI program. Also, we have classroom activity observing the stars and planets. In March 1998, we set up a Sun observation system and could observe the Sun

形容詞の副詞的用法に関する補説 : 「うれしい」「楽しい」を例に

本稿では、副詞的用法の成り立ちやすさは形容詞によって異なるという考えに基づき、「うれしい」と「楽しい」を例に、副詞的用法の成り立ちやすさに関わる要因を探った。類義語である「うれしい」と「楽しい」とは、「うれしい」のほうが副詞的用法が成り立ちにくいという違いがある。その要因として、「うれしい」が述語として属性叙述文がとりにくいという点、さらに、「うれしい」が「即時的な反応」であり、持続性を欠く心理状態を表すという点を挙げた

Characteristic Grammatical Items of Each Language Skill: Analyzing Eight Kinds of Corpora to Reconsider the Grammar Syllabus for International Students Learning Academic Japanese

短期の交換留学生の増加や留学生の留学目的の多様化にともない，長期学習を前提とした従来の日本語学習シラバスは，学習者のニーズに必ずしも合わなくなってきている。その問題は現行の文法シラバスにおいて顕著であると思われる。学習をより実用的なものにするには，扱う文法項目を再考し，真に必要なものに厳選する必要がある。本研究では，一定の基準に基づき文法項目を抽出したうえで，言語活動という観点から選出した8種類のコーパスを用いて使用頻度(100万語換算)，出現順位，および，4技能別の特徴項目を洗い出した。技能別の特徴項目の抽出は，各文法項目をどのような言語活動の中で扱うかを考えるための一助となる。本調査の結果は，実践的な活動を可能とする学習体系のデザインのための基礎資料となると考える

Grammar Syllabus Reconstruction Based on Japanese Corpora: Selecting Minimum Contents Required for Academic Achievement

Ｉ. 論文学習者の多様化に伴い、国内外の高等教育機関では、日本語を主専攻としない日本語学習者も増えてきているが、そうした学習者にとって、現行の緻密な語彙・文法学習からなる長期的な学習を前提とした日本語学習体系はあまり魅力的なものとなっていないと考えられる。このような日本語学習者の学習意欲を維持するためには、時間的制約の多いなかでも、各自の知的関心に見合う、質の高いアカデミックな学びを実感できる新たな日本語学習シラバスが必要なのではないか。こうした問題意識から、本研究では、高等教育機関で学ぶ留学生のための、学びやすく、かつ、上達を実感できる学習体系の新たな構築を目指し、太田・永谷・中石（2018）で報告された8種類のコーパスデータの分析に基づいて選定された265項目の文法項目を対象に、出現頻度と技能別の特徴項目の情報を活かした学習の段階づけを試み、初級から上級までの新しい文法シラバスを提案した

MicroRNA-140 mediates RB tumor suppressor function to control stem cell-like activity through interleukin-6

We established an in vitro cell culture system to determine novel activities of the retinoblastoma (Rb) protein during tumor progression. Rb depletion in p53-null mouse-derived soft tissue sarcoma cells induced a spherogenic phenotype. Cells retrieved from Rb-depleted spheres exhibited slower proliferation and less efficient BrdU incorporation, however, much higher spherogenic activity and aggressive behavior. We discovered six miRNAs, including mmu-miR-18a, -25, -29b, -140, -337, and -1839, whose expression levels correlated tightly with the Rb status and spherogenic activity. Among these, mmu-miR-140 appeared to be positively controlled by Rb and to antagonize the effect of Rb depletion on spherogenesis and tumorigenesis. Furthermore, among genes potentially targeted by mmu-miR-140, Il-6 was upregulated by Rb depletion and downregulated by mmu-mir-140 overexpression. Altogether, we demonstrate the possibility that mmu-mir-140 mediates the Rb function to downregulate Il-6 by targeting its 3′-untranslated region. Finally, we detected the same relationship among RB, hsa-miR-140 and IL-6 in a human breast cancer cell line MCF-7. Because IL-6 is a critical modulator of malignant features of cancer cells and the RB pathway is impaired in the majority of cancers, hsa-miR-140 might be a promising therapeutic tool that disrupts linkage between tumor suppressor inactivation and pro-inflammatory cytokine response