Biological effects of inner-shell photoabsorption induced by monochromatized soft X-rays on yeast cells

Thesis (Ph.D.)--University of Tsukuba, (B), no. 748, 1992.3.2

DNA damage and repair kinetics after microbeam radiation therapy emulation in living cells using monoenergetic synchrotron X-ray microbeams

The molecular response of mammalian cells to a monoenergetic synchrotron X-ray microbeam which emulated microbeam radiation configurations has been investigated. Very few γH2AX foci were found outside the irradiated zone within 1 h of irradiation, even within a single nucleus. Furthermore, 12 h after radiation there was a large decrease in foci number but many cells still contained γH2AX foci, of which many were outside the directly irradiated regions

EGUIDE project and treatment guidelines

Aim: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the ‘Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)’ integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. Methods: Four hundred thirteen out of 461 psychiatrists attended two 1‐day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants’ clinical knowledge of the treatment guidelines using self‐completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants’ demographics and their clinical knowledge scores. Results: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. Conclusion: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants’ clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders

Phosphorylation by Dyrk1A of Clathrin Coated Vesicle-Associated Proteins: Identification of the Substrate Proteins and the Effects of Phosphorylation

Dyrk1A phosphorylated multiple proteins in the clathrin-coated vesicle (CCV) preparations obtained from rat brains. Mass spectrometric analysis identified MAP1A, MAP2, AP180, and α- and β-adaptins as the phosphorylated proteins in the CCVs. Each protein was subsequently confirmed by [32P]-labeling and immunological methods. The Dyrk1A-mediated phosphorylation released the majority of MAP1A and MAP2 and enhanced the release of AP180 and adaptin subunits from the CCVs. Furthermore, Dyrk1A displaced adaptor proteins physically from CCVs in a kinase-concentration dependent manner. The clathrin heavy chain release rate, in contrast, was not affected by Dyrk1A. Surprisingly, the Dyrk1A-mediated phosphorylation of α- and β-adaptins led to dissociation of the AP2 complex, and released only β-adaptin from the CCVs. AP180 was phosphorylated by Dyrk1A also in the membrane-free fractions, but α- and β-adaptins were not. Dyrk1A was detected in the isolated CCVs and was co-localized with clathrin in neurons from mouse brain sections and from primary cultured rat hippocampus. Previously, we proposed that Dyrk1A inhibits the onset of clathrin-mediated endocytosis in neurons by phosphorylating dynamin 1, amphiphysin 1, and synaptojanin 1. Current results suggest that besides the inhibition, Dyrk1A promotes the uncoating process of endocytosed CCVs

Targeting Specific Sites in Biological Systems with Synchrotron X-Ray Microbeams for Radiobiological Studies at the Photon Factory

X-ray microbeams have been used to explore radiobiological effects induced by targeting a specific site in living systems. Synchrotron radiation from the Photon Factory, Japan, with high brilliance and highly parallel directionality is a source suitable for delivering a particular beam size or shape, which can be changed according to target morphology by using a simple metal slit system (beam size from 5 μm to several millimeters). Studies have examined the non-targeted effects, called bystander cellular responses, which are thought to be fundamental mechanisms of low-dose or low-dose-rate effects in practical radiation risk research. Narrow microbeams several tens of micrometers or less in their size targeted both the cell nucleus and the cytoplasm. Our method combined with live-cell imaging techniques has challenged the traditional radiobiological dogma that DNA damage is the only major cause of radiation-induced genetic alterations and is gradually revealing the role of organelles, such as mitochondria, in these biological effects. Furthermore, three-dimensionally cultured cell systems have been used as microbeam targets to mimic organs. Combining the spatial fractionation of X-ray microbeams and a unique ex vivo testes organ culture technique revealed that the tissue-sparing effect was induced in response to the non-uniform radiation fields. Spatially fractionated X-ray beams may be a promising tool in clinical radiation therapy

Targeting Specific Sites in Biological Systems with Synchrotron X-Ray Microbeams for Radiobiological Studies at the Photon Factory

X-ray microbeams have been used to explore radiobiological effects induced by targeting a specific site in living systems. Synchrotron radiation from the Photon Factory, Japan, with high brilliance and highly parallel directionality is a source suitable for delivering a particular beam size or shape, which can be changed according to target morphology by using a simple metal slit system (beam size from 5 μm to several millimeters). Studies have examined the non-targeted effects, called bystander cellular responses, which are thought to be fundamental mechanisms of low-dose or low-dose-rate effects in practical radiation risk research. Narrow microbeams several tens of micrometers or less in their size targeted both the cell nucleus and the cytoplasm. Our method combined with live-cell imaging techniques has challenged the traditional radiobiological dogma that DNA damage is the only major cause of radiation-induced genetic alterations and is gradually revealing the role of organelles, such as mitochondria, in these biological effects. Furthermore, three-dimensionally cultured cell systems have been used as microbeam targets to mimic organs. Combining the spatial fractionation of X-ray microbeams and a unique ex vivo testes organ culture technique revealed that the tissue-sparing effect was induced in response to the non-uniform radiation fields. Spatially fractionated X-ray beams may be a promising tool in clinical radiation therapy

Radio-adaptive response induced by the targeted cytoplasmic irradiation in normal human fibroblasts with X-ray microbeams

高エネルギー加速器研究機構放射光科学研究施設での放射光共同研究課題『細胞質へのX線照射がトリガーとなる放射線適応応答へのバイスタンダー効果の関与』（課題番号：2021G539、課題代表者：鈴木雅雄）において、放射光X線マイクロビーム細胞照射装置を駆使して、ヒト培養細胞の細胞核または細胞質のみに限定的にX線を照射したときの細胞応答（バイスタンダー効果）の現象論と誘導メカニズム解明を目的とし計画した