Role of Kupffer cells in liver injury induced by CpG oligodeoxynucleotide and flucloxacillin in mice

CpG oligodeoxynucleotide (CpG-ODN) is a Toll-like receptor 9 (TLR9) agonist that can induce innate immune responses. In a previous study, flucloxacillin (FLUX; 100 mg/kg, gavage)-induced liver injury in mice was enhanced by co-administration of CpG-ODN (40 μg/mouse, intraperitoneally). In this study, the mechanism of CpG-ODN sensitization to FLUX-induced liver injury was further investigated in mice inhibited of Kupffer cells (KCs) function by gadolinium chloride (GdCl3; 10 mg/kg, intravenously). GdCl3-treated mice administrated with CpG-ODN and FLUX showed lower liver injury than wild-type (WT) mice treated with CpG-ODN and FLUX. Upregulation of Fas and FasL by CpG-ODN was also inhibited in GdCl3-treated mice and mitochondrial swelling in response to FLUX failed to occur regardless of pre-treatment with CpG-ODN. When FasL-mutant gld/gld mice were treated with CpG-ODN, mitochondrial swelling in response to FLUX was also inhibited. These results suggest that KCs play an essential role in liver injury induced by CpG-ODN and FLUX. CpG-ODN may activate KCs, resulting in induction of Fas/FasL-mediated apoptosis of hepatocytes. The Fas/FasL pathway may also be an upstream regulator of CpG-ODN- and FLUX-induced changes in mitochondrial permeability transition. These results enhance our understanding of the mechanism of the adjuvant effect of CpG-ODN in this mouse model of liver injury

A Study on Deep Learning of Teachers in School Workshop

校内研修会において教員が求める深い学びの様相を明らかにするために，秋田県の小学校，中学校の教員が「どのような学びがあれば深いと感じるか」について質問紙調査を行った．自由記述法で得られた回答について，テキストマイニング分析から 2 カテゴリー，内容の質的分類からは 5 カテゴリーを抽出することができた．これらの関係をKolbの経験学習サイクルモデル，野中の組織的知識創造の基本原理（SECIモデル）を用いて考察した．その結果，教員が求める深い学びとして，内容・理解，プロセス・思考という 2 つのカテゴリーに加えて，実践への意欲化という第三のカテゴリーがあることを見いだした．In order to clarify the aspect of deep learning required by teachers at the in-school workshop, we conducted a questionnaire survey of elementary and junior high school teachers in Akita Prefecture about "what kind of learning would make them feel deep". Regarding the answers obtained by the free description method, two categories could be extracted from the text mining analysis，and five categories could be extracted from the qualitative classification of the contents. Then we considered these relationships using“Kolb‘s experiential learning cycle model”,“Nonaka‘s basic principles of organizational knowledge creation（SECI model）” As deep learning required by teachers, we found that in addition to the two categories of content / understanding and process / thinking, there is a third category of motivation for practice

Drug-induced altered self-presentation increases tumor immunogenicity

Anti-human immunodeficiency virus (HIV) drug abacavir (ABC) binds to the specific allele of human leukocyte antigen (HLA-B*57:01) and activates CD8+ T cells by presenting altered abnormal peptides. Here, we examined the effect of ABC-induced altered self-presentation by HLA-B*57:01 on immunogenicity of cancer cells and CD8+ T-cell-dependent anti-tumor immunity. We established human-mouse chimeric HLA-B*57:01-expressing tumor cell lines (B16F10 and 3LL) and tested the anti-tumor effect of ABC in vivo. ABC treatment inhibited the growth of HLA-B*57:01-expressing tumors by a CD8+ T-cell-dependent mechanism. ABC treatment induced CXCR3-dependent infiltration of CD8+ T cells into HLA-B*57:01-expressing tumors, and activated those tumor-infiltrating CD8+ T cells to proliferate and secrete IFN-γ. The activation of CD8+ T cells using drug-induced altered self-presentation may be a new strategy to increase tumor immunogenicity and improve the efficacy of immunotherapy