ドイツスポーツ史の発展に向けた１０の命題 : クリスティアーネ・アイゼンベルク「スポーツ史における社会学，経済学そして『文化経済学』のアプローチ : 新しい方向のための提言」に対するコメント

departmental bulletin pape

Mechanisms of multidrug resistance caused by an Ipi1 mutation in the fungal pathogen Candida glabrata

Multidrug resistance in the pathogenic fungus Candida glabrata is a growing global threat. Here, we study mechanisms of multidrug resistance in this pathogen. Exposure of C. glabrata cells to micafungin (an echinocandin) leads to the isolation of a mutant exhibiting resistance to echinocandin and azole antifungals. The drug-resistant phenotype is due to a non-synonymous mutation (R70H) in gene IPI1, which is involved in pre-rRNA processing. Azole resistance in the ipi1R70H mutant depends on the Pdr1 transcription factor, which regulates the expression of multidrug transporters. The C. glabrata Ipi1 protein physically interacts with the ribosome-related chaperones Ssb and Ssz1, both of which bind to Pdr1. The Ipi1-Ssb/Ssz1 complex inhibits Pdr1-mediated gene expression and multidrug resistance in C. glabrata, in contrast to Saccharomyces cerevisiae where Ssz1 acts as a positive regulator of Pdr1. Furthermore, micafungin exposure reduces metabolic activity and cell proliferation in the ipi1R70H mutant, which may contribute to micafungin tolerance.Citation: Taiga Miyazaki, Shintaro Shimamura, Yohsuke Nagayoshi, Hironobu Nakayama, Akihiro Morita, Yutaka Tanaka, Yasuhiko Matsumoto, Tatsuo Inamine, Hiroshi Nishikawa, Nana Nakada, Makoto Sumiyoshi, Tatsuro Hirayama, Shigeru Kohno, Hiroshi Mukae, Mechanisms of multidrug resistance caused by an Ipi1 mutation in the fungal pathogen Candida glabrata, Nature Communications, 16(1), 2025-01-25, https://doi.org/10.1038/s41467-025-56269-

Pitt candidaemia score as an assessment tool for mortality in patients with candidaemia caused by Candida tropicalis and other Candida species: a multicentre study conducted in Japan

Background A bedside scoring system to assess the severity of disease is lacking for candidaemia. The Pitt candidaemia score (PCS) was evaluated for its association with mortality. Methods The PCS consists of five components, namely dialysis, hypotension, mechanical ventilation, cardiac arrest and mental status. Patients were classified into four categories according to their PCS. The correlation between PCS category at blood culture collection and 30 day mortality was studied individually for five Candida species. Results Leading rates of mortality were observed in Candida tropicalis and Candida krusei. The interval from inoculation to positive culture was 19.4 ± 9.7 h for C. tropicalis and 21.3 ± 5.6 h for C. krusei; these intervals were significantly shorter than those for other Candida species. In a Kaplan–Meier survival curve, a significant risk stratification by PCS category was demonstrated in all Candida species. A high PCS was an independent risk factor for mortality, and source control decreased the risk for C. tropicalis and Candida glabrata infections. Regarding antifungal therapy, the median PCS was 8 for liposomal amphotericin B, 2 for echinocandins and 0 for azoles, and this trend was consistent among four Candida species. Conclusions The mortality rate was well stratified by the PCS, and the PCS affected the selection of antifungals. A future prospective study is required for the PCS in guiding therapy for candidaemia

Cerebral radiation necrosis successfully treated with high-dose bevacizumab

Cerebral radiation necrosis (CRN) is a late complication that can occur after the treatment of a brain tumor with focal radiation therapy, particularly stereotactic radiosurgery (SRS). Since an excessive production of vascular endothelial growth factor (VEGF) from necrotic lesions is a possible etiology of radiation necrosis, the anti-VEGF antibody bevacizumab has been reported as an effective treatment option. We report a case of a 71-year-old Japanese male with CRN following SRS, successfully treated with bevacizumab. He had presented with aphasia and right lower-limb muscle weakness 6 years after a left upper lobectomy for lung adenocarcinoma. Head magnetic resonance imaging (MRI) showed a metastatic brain tumor in the left temporal lobe. A craniotomy and pre- and post-operative SRS treatments were performed to relieve his neurological symptoms. Although initial symptom improvement was observed, the patient developed lower-limb muscle weakness and aphasia symptoms 7 months after the last SRS treatment. 11C-methionine positron emission tomography (PET) and 18F-fluorodeoxyglucose PET scans showed no abnormal uptake, leading to a diagnosis of CRN. The patient was treated with bevacizumab 15 mg/kg every 3 weeks for six cycles. The bevacizumab treatment resulted in an improvement of neurological symptoms and lesions showing gadolinium-enhancing effects and high-signal areas on T2-weighted fluid attenuated inversion recovery on MRI. The improvement was maintained 44 months after the completion of the last bevacizumab treatment. Although no definitive number of cycles and dosage of bevacizumab for CRN have been established, this case suggests that administering six cycles of bevacizumab may prevent long-term recurrence of CRN

Production of Prompt Charmonia in e+e- Annihilation at sqrt[s] ≈ 10.6 GeV

journal articl

植物懸濁培養細胞のプロトプラスト化最適反応条件の定量的設定法の開発

筑波大学University of Tsukuba博士（農学）Doctor of Philosophy in Agricultural Science従来、新規な能力(耐病性、耐寒性、および高生産性など)を有する植物体の作製には主に交雑育種法が用いられてきた。しかし、交雑育種法には以下の問題点がある。①植物の交雑できる範囲は限られているため多くの場合近縁種間 ...1992付: 参考文献doctoral thesi

＜書評＞田中拓道『福祉政治史―格差に抗するデモクラシー』（勁草書房、2017年）

departmental bulletin pape

Inanimate exploration in the novel object recognition task.

<p>(A–C) Total time of exploration of two identical objects (O1, both on left and right side) during the training session for three conditional CB1 receptor mutant lines (Glu-CB1 [n = 23+13], GABA-CB1 [n = 18+23], D1-CB1 [12+12]) and their wild-type control littermates. (D–F) Total time of exploration of familiar object (O1) and novel object (O2 or O3) during the retention session after 2 h or 24 h (G–I). Glu-CB1^−/− mice displayed a reduced exploration, while GABA-CB1^−/− mice showed an increased exploration both in the training and retention session when compared to their wild-type littermate controls. No significant genotype differences were observed in the D1-CB1 mutant line. 2-way ANOVA (genotype differences) *p<0.05, ***p<0.001; t-test (discrimination index DI) ^#p<0.05.</p

Animate vs. inanimate exploration in the sociability test.

<p>(A–C) Comparison of animate (mouse) and inanimate (object, “empty”) exploration for the three mutants lines (Glu-CB1 [n = 22+13], GABA-CB1 [n = 18+23], D1-CB1 [16+16]) and their wild-type littermate controls during the sociability phase. (D–F) Exploration of the familiar and the novel interaction partner for during the social novelty phase. Glu-CB1^−/− mice displayed no significant change in the exploration session, where there was a choice between the object and the interaction partner. In the social novelty phase, however, the interaction with a novel interaction partner was decreased when compared with their wild-type littermate controls. GABA-CB1^−/− mice showed an increased social interaction in both sessions. In the D1-CB1 mutant line, no genotype differences were observed neither in the sociability nor in the social novelty phase. n = 11–20 animals; t-test *p<0.05, **p<0.01.</p

Cre recombinase-activated transgene expression.

<p><b>A</b>, AAV expression cassette. Top, Silencing of transgene expression by transcriptional termination cassette containing three polyadenylation sites flanked by loxP sites (triangles). Bottom, Cre recombinase-mediated excision of the Stop cassette leading to transcription of the transgene. ITR, inverted terminal repeat; CBA, chicken-β-actin promoter; 3xpA, three polyadenylation (pA) signals; GOI, gene of interest; WPRE, woodchuck hepatitis virus post-transcriptional regulatory element. <b>B–G</b>, HEK cells were co-transfected with pAAV-Stop-GFP and pAAV-Cre (B–D) or pAAV-empty (E–G) and GFP immunofluorescence is strictly limited to Cre transfectants. Transgene expression is tightly inhibited when pAAV-Stop-GFP is co-transfected with pAAV-empty. Blue: cell nucleus staining with DAPI, Green: GFP immunostaining, Red: Cre recombinase immunostaining. Bar in G: 50 µm. <b>H–P</b>, Two months after stereotaxic vector delivery (AAV-GFP or AAV-Stop-GFP) to the dorsal hippocampus of adult wild-type or NEX-Cre mice, GFP epifluorescence was assessed in brain sections. <b>H–J</b>, AAV-GFP efficiently transduces all types of neurons of the hippocampal formation, in particular in CA1, CA2, CA3, the hilar region and the dentate gyrus. Note that transduced interneurons (arrowheads in H) can be visualized in areas of low GFP abundance. GC, granule cell layer; Hil, hilar region; LMol, stratum lacunosum-molecularis; Mol, stratum molecularis; Or, stratum oriens; Pyr, CA1/CA3 pyramidal cell layer; Rad, stratum radiatum. <b>K–M</b>, After AAV-Stop-GFP injection, GFP expression was not detectable in wild-type mice. <b>N–P</b>, In NEX-Cre mice, neurons of the pyramidal cell layer express the reporter gene, while granule cells of the dentate gyrus are spared. Note that in this mouse line, Cre recombinase is not expressed in the adult dentate gyrus (see Goebbels et al., 2006). Bar in M: 250 µm.</p