Trials in development of a scheme of the educational guidance based on “the Layer model of mathematical activities”

　これまで数多く用いられてきた「数学的活動」について，本校における視点で再考するとともに，新しく改訂される学習指導要領に示される指導内容についても検討する。その具体として教科書の構成を「数学的活動のレイヤー論」の視点で捉え直す。これまで一つの単元で構成されがちであったカリキュラム設計を，単元や領域の枠を超えて組み直すことで，課題に対し様々なアプローチを可能とし，より深化した数学的活動を目指すこととなる。本年度は模索しながらもその実践を繰り返すことで数学的活動をどのように捉え直すことができるかを考え，その成果と課題について考察した。 / 　While reviewing various traditionally used “mathematical activities” from a viewpoint shared in our junior high school, we examined teaching contents exhibited by Education Ministry Guidelines which are supposed to be newly revised. As a result of the review, we propose a revision of composition of math textbooks in terms of the “Layer model of mathematical activities”. We also provide more elaborated mathematical activities that enable various approaches to a problem, by restructuring curriculum designs, that have been often structured by a single course unit, beyond the frames of course units or disciplines. In this paper we also discuss results and problems emerged from our trials and practices of these improved mathematical activities

学校運営協議会における保護者の位置

学位の種別:課程博士University of Tokyo(東京大学

Beneficial Effects of Cocoa in Perivascular Mato Cells of Cerebral Arterioles in SHR-SP (Izm) Rats

As previously reported, the cerebral arterioles are surrounded by unique perivascular Mato cells. They contain many inclusion bodies rich in hydrolytic enzymes, and have strong uptake capacity. They are thus considered scavenger cells of vascular and neural tissues in steady-state. In this study, employing hypertensive SHR-SP (Izm) rats, the viability of Mato cells was investigated. In hypertensive rats, the capacity for uptake of horse radish peroxidase (HRP) and the activity of acid phosphatase (ACPase) of Mato cells were markedly reduced, and on electron-microscopic examination Mato cells were found to include heterogeneous contents and appeared electron-dense and degenerated. Vascular cells exhibited some signs of pathology. However, in hypertensive rats fed chow containing 0.25% cocoa, the uptake capacity and ACPase activity of Mato cells for HRP were enhanced, and on electron-microscopic examination Mato cells appeared healthy, with mitochondria with nearly normal profiles. Signs of pathology in vascular cells were also decreased. Superoxides may impair Mato cells and vascular cells

A Genetic Variant in the IL-17 Promoter Is Functionally Associated with Acute Graft-Versus-Host Disease after Unrelated Bone Marrow Transplantation

Interleukin IL-17 is a proinflammatory cytokine that has been implicated in the pathogenesis of various autoimmune diseases. The single nucleotide polymorphism (SNP), rs2275913, in the promoter region of the IL-17 gene is associated with susceptibility to ulcerative colitis. When we examined the impact of rs2275913 in a cohort consisting of 438 pairs of patients and their unrelated donors transplanted through the Japan Marrow Donor Program, the donor IL-17 197A allele was found to be associated with a higher risk of acute graft-versus-host disease (GVHD; hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.00 to 2.13; P = 0.05). Next, we investigated the functional relevance of the rs2275913 SNP. In vitro stimulated T cells from healthy individuals possessing the 197A allele produced significantly more IL-17 than those without the 197A allele. In a gene reporter assay, the 197A allele construct induced higher luciferase activity than the 197G allele, and the difference was higher in the presence of T cell receptor activation and was abrogated by cyclosporine treatment. Moreover, the 197A allele displayed a higher affinity for the nuclear factor activated T cells (NFAT), a critical transcription factor involved in IL-17 regulation. These findings substantiate the functional relevance of the rs2275913 polymorphism and indicate that the higher IL-17 secretion by individuals with the 197A allele likely accounts for their increased risk for acute GVHD and certain autoimmune diseases

Role of Tumor-Associated Macrophages in Sarcomas

Simple Summary Recent studies have shown the pro-tumoral role of tumor-associated macrophages (TAMs) not only in major types of carcinomas but also in sarcomas. Several types of TAM-targeted drugs have been investigated under clinical trials, which may represent a novel therapeutic approach for bone and soft-tissue sarcomas. Sarcomas are complex tissues in which sarcoma cells maintain intricate interactions with their tumor microenvironment. Tumor-associated macrophages (TAMs) are a major component of tumor-infiltrating immune cells in the tumor microenvironment and have a dominant role as orchestrators of tumor-related inflammation. TAMs promote tumor growth and metastasis, stimulate angiogenesis, mediate immune suppression, and limit the antitumor activity of conventional chemotherapy and radiotherapy. Evidence suggests that the increased infiltration of TAMs and elevated expression of macrophage-related genes are associated with poor prognoses in most solid tumors, whereas evidence of this in sarcomas is limited. Based on these findings, TAM-targeted therapeutic strategies, such as inhibition of CSF-1/CSF-1R, CCL2/CCR2, and CD47/SIRP alpha, have been developed and are currently being evaluated in clinical trials. While most of the therapeutic challenges that target sarcoma cells have been unsuccessful and the prognosis of sarcomas has plateaued since the 1990s, several clinical trials of these strategies have yielded promising results and warrant further investigation to determine their translational benefit in sarcoma patients. This review summarizes the roles of TAMs in sarcomas and provides a rationale and update of TAM-targeted therapy as a novel treatment approach for sarcomas

CCN3 (NOV) Drives Degradative Changes in Aging Articular Cartilage

Aging is a major risk factor of osteoarthritis, which is characterized by the degeneration of articular cartilage. CCN3, a member of the CCN family, is expressed in cartilage and has various physiological functions during chondrocyte development, differentiation, and regeneration. Here, we examine the role of CCN3 in cartilage maintenance. During aging, the expression of Ccn3 mRNA in mouse primary chondrocytes from knee cartilage increased and showed a positive correlation with p21 and p53 mRNA. Increased accumulation of CCN3 protein was confirmed. To analyze the effects of CCN3 in vitro, either primary cultured human articular chondrocytes or rat chondrosarcoma cell line (RCS) were used. Artificial senescence induced by H2O2 caused a dose-dependent increase in Ccn3 gene and CCN3 protein expression, along with enhanced expression of p21 and p53 mRNA and proteins, as well as SA-beta gal activity. Overexpression of CCN3 also enhanced p21 promoter activity via p53. Accordingly, the addition of recombinant CCN3 protein to the culture increased the expression of p21 and p53 mRNAs. We have produced cartilage-specific CCN3-overexpressing transgenic mice, and found degradative changes in knee joints within two months. Inflammatory gene expression was found even in the rib chondrocytes of three-month-old transgenic mice. Similar results were observed in human knee articular chondrocytes from patients at both mRNA and protein levels. These results indicate that CCN3 is a new senescence marker of chondrocytes, and the overexpression of CCN3 in cartilage may in part promote chondrocyte senescence, leading to the degeneration of articular cartilage through the induction of p53 and p21