Molecular characterization of an estrogen receptor and estrogen-related receptor and their autoregulatory capabilities in two Mytilus species

Vertebrate-like sex steroid hormones have been widely detected in mollusks, and numerous experiments have shown the importance of steroids in gonad development. Nevertheless, their signaling pathways in invertebrates have not been uncovered yet. Steroid receptors are an ancient class of transcription factors with multiple roles in not only vertebrates but also invertebrates. Estrogen signaling is thought to have major roles in mollusk physiology, but the full repertoire of estrogen receptors is unknown. We presented the successful cloning of two novel forms of estrogen receptor-like genes. These receptors are present in two closely related species of Mytilus: Mytilus edulis and Mytilus galloprovincialis, commonly known and widely distributed sentinel species. Our phylogenetic analysis revealed that one of these receptors is an estrogen receptor (ER) and the other one is an estrogen-related receptor (ERR). Studies of expression analysis showed that both receptor mRNAs were localized in the oocytes and follicle cells in contact with developing oocytes in the ovary and Sertoli cells in the testis, and in the ciliated cells of the gill. In addition, we have evidence that one (ER) of these may have a capacity to autoregulate its own expression in the gonadal cells by estrogen (E2) and that this gene is responsive to estrogenic compounds

miR-155, a Modulator of FOXO3a Protein Expression, Is Underexpressed and Cannot Be Upregulated by Stimulation of HOZOT, a Line of Multifunctional Treg

MicroRNAs (miRNAs) play important roles in regulating post-transcriptional gene repression in a variety of immunological processes. In particular, much attention has been focused on their roles in regulatory T (Treg) cells which are crucial for maintaining peripheral tolerance and controlling T cell responses. Recently, we established a novel type of human Treg cell line, termed HOZOT, multifunctional cells exhibiting a CD4+CD8+ phenotype. In this study, we performed miRNA profiling to identify signature miRNAs of HOZOT, and therein identified miR-155. Although miR-155 has also been characterized as a signature miRNA for FOXP3+ natural Treg (nTreg) cells, it was expressed quite differently in HOZOT cells. Under both stimulatory and non-stimulatory conditions, miR-155 expression remained at low levels in HOZOT, while its expression in nTreg and conventional T cells remarkably increased after stimulation. We next searched candidate target genes of miR-155 through bioinformatics, and identified FOXO3a, a negative regulator of Akt signaling, as a miR-155 target gene. Further studies by gain- and loss-of-function experiments supported a role for miR-155 in the regulation of FOXO3a protein expression in conventional T and HOZOT cells

母児同室における初産婦のニーズと支援について─ KJ 法を用いた分析（第2報）─

　「母乳育児成功のための10か条」はWHO/UNICEF が1989年に発表した「母乳育児の保護，推進，支援，産科医 療施設の特別な役割」の要約である．これは「Baby Friendly Hospital Initiative：赤ちゃんにやさしい病院運動」の 基本方針でもあり，母児同室を推奨している． 　今回，個室にて母児同室を開始した初産婦の語りをKJ 法で分析し，ニーズと看護支援について検討した． 　その結果，看護者に期待する支援の内容は《常に気にかけて訪室してくれる》《頻回に言葉をかけてほしい》《看 護者たちの指導力や十分な心遣い》の3つのカテゴリーで構成された．《常に気にかけて訪室してくれる》は〈もっ と来て声をかけてほしい〉〈呼ばなくても見に来てくれる〉〈夜も目を向けてほしい〉のサブカテゴリー，《頻回に 訪室してくれる》は〈言いたくても自分だけかと躊躇する〉〈初産婦の特性〉のサブカテゴリーで，また《看護者 たちの指導力や十分な心遣い》は〈指導以外でも看護者の心遣いを感じる〉〈看護者から学ぶことが多い〉の2つの サブカテゴリーで構成されていた．母親たちの殆どは，初産のため些細な不安で看護者を呼ぶのを躊躇していた． 母親たちにとって指導のほか，看護者がすることをまねて学ぶとことも大きかった． 　看護者は常に意識を離さず，母親たちに対してプロの目があることを伝え，支え見守っているという保証を示す ことが重要である．“10 Steps to Successful Breast-feeding” is a summary of“ Protecting, promoting and supporting breast-feeding: the special role of maternity services” which was published by WHO/UNICEF in 1989 and is the basic policy of“ Baby Friendly Hospital Initiative”, which recommends rooming-in. In this study, the support from nurses to their needs described by primiparas who started rooming-in with the mother was analyzed using the KJ method. Results showed that the detailed expected support provided by nurses were broken down into the following three categories:“ Nurses often visit rooms with care”,“ Mothers wish for nurses to frequently speak to them”, and“ Nurses’ leadership and substantial care”. Each category consisted of the subcategories:‘ Visit more often’,‘ Visit without asking’, and‘ Watch at night as well’ in“ Nurses often visit rooms with care”;‘ Hesitate to call thinking that I am only one to do so’ and‘ Characteristic of primiparas’ in“ Mothers wish for nurses to frequently speak to them”;‘ Feel care from nurses other than guidance’ and‘ Learn many things from nurses’ in “Nurses’ leadership and substantial care”. Most mothers were hesitant to call nurses for trivial concerns due to it being their first deliveries. Mothers often learned by copying what nurses did, in addition to learning from guidance. It was suggested that it was important to give assurance that nurses were supporting and keeping a constant eye on the mothers, and to communicate to mothers that they were being supported by professionals

Cattle Performance Improvement Trials in Southeast Asian Countries, Using Japanese Cattle

The Project was designed to improve the performance of cattle in Southeast Asia, using Japanese Cattle, Frozen semen of the Japanese Brown breed of cattle was send by air to Manado, North sulawesi, lndonesia. The frozen semen was inseminated to P. O. (Peranakan Ongole) cow. A female hybrid (F1) was produced after duration of pregnancy of 289 days. This is the first hybrid of cattle between Japanese Brown breed cattle and Peranakan Ongole in lndonesia. We call F1 of crossbreed of Ongole with Japanese Brown breed cattle, Jabragole.この研究は日本の牛を用いて東南アジヤの牛の能力を改善するために計画した。日本の褐毛和種牛の凍結精液をインドネシア・北スラウエシのマナドに空輸した。この凍結精液をP.Ongole雌牛に人工授精した。289日の妊娠期間の後に1頭の雌雑種牛F1が生まれた。F1は日本の褐毛和種とオンゴール牛との間に生まれた最初の交雑種F1である。私どもはこれをジャブラゴール(Jabragole)と名付けた

Novel functional anti-HER3 monoclonal antibodies with potent anti-cancer effects on various human epithelial cancers

Resistance of progressive cancers against chemotherapy is a serious clinical problem. In this context, human epidermal growth factor receptor 3 (HER3) can play important roles in drug resistance to HER1- and HER2- targeted therapies. Since clinical testing of anti-HER3 monoclonal antibodies (mAbs) such as patritumab could not show remarkable effect compared with existing drugs, we generated novel mAbs against anti-HER3. Novel rat mAbs reacted with HEK293 cells expressing HER3, but not with cells expressing HER1, HER2 or HER4. Specificity of mAbs was substantiated by the loss of mAb binding with knockdown by siRNA and knockout of CRISPR/Cas9-based genome-editing. Analyses of CDR sequence and germline segment have revealed that seven mAbs are classified to four groups, and the binding of patritumab was inhibited by one of seven mAbs. Seven mAbs have shown reactivity with various human epithelial cancer cells, strong internalization activity of cell-surface HER3, and inhibition of NRG1 binding, NRG1-dependent HER3 phosphorylation and cell growth. Anti-HER3 mAbs were also reactive with in vivo tumor tissues and cancer tissue-originated spheroid. Ab4 inhibited in vivo tumor growth of human colon cancer cells in nude mice. Present mAbs may be superior to existing anti-HER3 mAbs and support existing anti-cancer therapeutic mAbs

Instructional Plan to Associate Exploration Activities in Three years' High School Curriculum for Developing Problem Solving Abilities ─ Practices Based on the Warp and Woof Model ─

P(論文)「総合的な探究の時間」の目標のひとつである“ 実社会や実生活と自己との関わりから問いを見いだし，自分で課題を立て，情報を集め，整理・分析して，まとめ・表現する”ことを達成するための指導計画を設計し，その実践を報告する．高校3年間にわたり問題解決の縦糸・横糸モデルを活用した明示的指導により，生徒は枠組みを意識して問題解決に取り組むことができるようになっていた．さらに今後は，主体的・対話的で深い学びの実現に向け，松田（2020）の新・逆向き設計手法を適用し，問題解決型授業実践から各教科において活用可能な知識内容を厳選し指導する方策を検討課題に位置付ける．departmental bulletin pape

Repurposing bromocriptine for Aβ metabolism in Alzheimer’s disease (REBRAnD) study : randomised placebo-controlled double-blind comparative trial and open-label extension trial to investigate the safety and efficacy of bromocriptine in Alzheimer’s disease with presenilin 1 (PSEN1) mutations

Introduction Alzheimer’s disease (AD) is one of the most common causes of dementia. Pathogenic variants in the presenilin 1 (PSEN1) gene are the most frequent cause of early-onset AD. Medications for patients with AD bearing PSEN1 mutation (PSEN1-AD) are limited to symptomatic therapies and no established radical treatments are available. Induced pluripotent stem cell (iPSC)-based drug repurposing identified bromocriptine as a therapeutic candidate for PSEN1-AD. In this study, we used an enrichment strategy with iPSCs to select the study population, and we will investigate the safety and efficacy of an orally administered dose of bromocriptine in patients with PSEN1-AD. Methods and analysis This is a multicentre, randomised, placebo-controlled trial. AD patients with PSEN1 mutations and a Mini Mental State Examination-Japanese score of ≤25 will be randomly assigned, at a 2:1 ratio, to the trial drug or placebo group (≥4 patients in TW-012R and ≥2 patients in placebo). This clinical trial consists of a screening period, double-blind phase (9 months) and extension phase (3 months). The double-blind phase for evaluating the efficacy and safety is composed of the low-dose maintenance period (10 mg/day), high-dose maintenance period (22.5 mg/day) and tapering period of the trial drug. Additionally, there is an open-labelled active drug extension period for evaluating long-term safety. Primary outcomes are safety and efficacy in cognitive and psychological function. Also, exploratory investigations for the efficacy of bromocriptine by neurological scores and biomarkers will be conducted. Ethics and dissemination The proposed trial is conducted according to the Declaration of Helsinki, and was approved by the Institutional Review Board (K070). The study results are expected to be disseminated at international or national conferences and published in international journals following the peer-review process