Rigid-body fitting to atomic force microscopy images for inferring probe shape and biomolecular structure

Atomic force microscopy (AFM) can visualize functional biomolecules near the physiological condition, but the observed data are limited to the surface height of specimens. Since the AFM images highly depend on the probe tip shape, for successful inference of molecular structures from the measurement, the knowledge of the probe shape is required, but is often missing. Here, we developed a method of the rigid-body fitting to AFM images, which simultaneously finds the shape of the probe tip and the placement of the molecular structure via an exhaustive search. First, we examined four similarity scores via twin-experiments for four test proteins, finding that the cosine similarity score generally worked best, whereas the pixel-RMSD and the correlation coefficient were also useful. We then applied the method to two experimental high-speed-AFM images inferring the probe shape and the molecular placement. The results suggest that the appropriate similarity score can differ between target systems. For an actin filament image, the cosine similarity apparently worked best. For an image of the flagellar protein FlhAC, we found the correlation coefficient gave better results. This difference may partly be attributed to the flexibility in the target molecule, ignored in the rigid-body fitting. The inferred tip shape and placement results can be further refined by other methods, such as the flexible fitting molecular dynamics simulations. The developed software is publicly available

ストリング法によるタンパク質構造変化解析

要旨あり生体高分子の揺らぎとダイナミクス－シミュレーションと実験の統計解析－研究詳

心室頻拍に於ける外科的標本の組織再構築の研究

金沢大学医学部・附属病院心室性頻拍(VT)の本態を明らかにする目的で、実験梗塞犬とVT臨床例を対象に電気生理学的および病理学的検討を行った。実験モデルとして多分枝結紮法による心筋梗塞作成後3週間以上経過した梗塞犬を用い、プログラム刺激法でVTを誘発し、心表面マッピング、心筋内4層からなる三次元マッピングを作製した。さらにコンピュ-タ-を用いて作製した立体再構築像との対比を行った。また、人VT臨床例も同様に術中マッピングと立体再構築像を対比検討し以下の結論を得た。1,VT実験例、臨床例の責任心筋病変部の病理学的構造を可視化し得た。2,三次元マッピングにより梗塞犬における持続性VTのリエントリ-路を示した。心表面マッピンング上、心表面リエントリ-と考えられるVTの興奮伝播像が、実際は心筋全層にわたり8の字状に伝播するマクロリエントリ-を心表面で二次元的に観察した像であることが示された。3,持続性VTの誘発された梗予犬では洞調律時、VT時ともに遅延電位が検出され、洞調律時の遅延電位検出部位はVT時の最早期興奮部行と一致した。また、VT時の遅延電位検出部位はリエントリ-路終末の機能的ブロック部位に一致した。4,立体再構築像の検討では最早期興奮部位には線維化、脂肪変性のなかで残存心筋が縁状ないし島状に存在する構造が観察されこれらの残存心筋は心内膜側心筋層と連絡し、VT時のリエントリ-回路を形成した。5,VT時に遅延電位の検出された部位でも島状に心筋が残存し最早期興奮部位と類似構造であった。6,臨床VT例の立体再構築像では最早期興奮部位に接して変性心筋層が見られ、遅延電位が検出された。変性により伝導性の低下した心筋層がリエントリ-の成立に必要な伝導遅延部位を形成した。7,最早期興奮部位と遅延電位検出部位には構造的類似性がありVTの根治には両者の廃絶が必要である。研究課題/領域番号:02670602, 研究期間(年度):1990出典：研究課題「心室頻拍に於ける外科的標本の組織再構築の研究」課題番号02670602（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-02670602/）を加工して作

Aldo–Keto Reductase 1B10 and Its Role in Proliferation Capacity of Drug-Resistant Cancers

The human aldo–keto reductase AKR1B10, originally identified as an aldose reductase-like protein and human small intestine aldose reductase, is a cytosolic NADPH-dependent reductase that metabolizes a variety of endogenous compounds, such as aromatic and aliphatic aldehydes and dicarbonyl compounds, and some drug ketones. The enzyme is highly expressed in solid tumors of several tissues including lung and liver, and as such has received considerable interest as a relevant biomarker for the development of those tumors. In addition, AKR1B10 has been recently reported to be significantly up-regulated in some cancer cell lines (medulloblastoma D341 and colon cancer HT29) acquiring resistance toward chemotherapeutic agents (cyclophosphamide and mitomycin c), suggesting the validity of the enzyme as a chemoresistance marker. Although the detailed information on the AKR1B10-mediated mechanisms leading to the drug resistance process is not well understood so far, the enzyme has been proposed to be involved in functional regulations of cell proliferation and metabolism of drugs and endogenous lipids during the development of chemoresistance. This article reviews the current literature focusing mainly on expression profile and roles of AKR1B10 in the drug resistance of cancer cells. Recent developments of AKR1B10 inhibitors and their usefulness in restoring sensitivity to anticancer drugs are also reviewed

Oseltamivir (Tamiflu®)-induced pneumonia

SummaryWe report the first case of oseltamivir-induced pneumonia. A 50-year-old man was diagnosed with influenza and prescribed oseltamivir. He had a persistent high fever, and developed a productive cough with peripheral blood eosinophilia and his chest radiograph showed ground glass opacity. Bronchoalveolar lavage fluid and histological findings obtained from transbronchial lung biopsy suggested eosinophilic pneumonia with component of cryptogenic organizing pneumonia. Drug lymphocyte stimulation test against oseltamivir was positive. In spite of discontinuation of oseltamivir, his condition did not ameliorate. He was treated with prednisolone for oseltamivir-induced lung injury and the symptoms improved immediately. We should recognize oseltamivir-induced pneumonia as a differential diagnosis in the case of developing pneumonia following treatment with oseltamivir

Oseltamivir (Tamiflu®)-induced pneumonia

SummaryWe report the first case of oseltamivir-induced pneumonia. A 50-year-old man was diagnosed with influenza and prescribed oseltamivir. He had a persistent high fever, and developed a productive cough with peripheral blood eosinophilia and his chest radiograph showed ground glass opacity. Bronchoalveolar lavage fluid and histological findings obtained from transbronchial lung biopsy suggested eosinophilic pneumonia with component of cryptogenic organizing pneumonia. Drug lymphocyte stimulation test against oseltamivir was positive. In spite of discontinuation of oseltamivir, his condition did not ameliorate. He was treated with prednisolone for oseltamivir-induced lung injury and the symptoms improved immediately. We should recognize oseltamivir-induced pneumonia as a differential diagnosis in the case of developing pneumonia following treatment with oseltamivir

「特集生体高分子の揺らぎとダイナミクス― シミュレー\\nションと実験の統計解析―」について

要旨なし生体高分子の揺らぎとダイナミクス－シミュレーションと実験の統計解析－その他・前書

Radioligand Assay-Based Detection of Antibodies against SARS-CoV-2 in Hospital Workers Treating Patients with Severe COVID-19 in Japan.

This study aimed to clarify whether infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is prevalent among the staff of a hospital providing treatment to patients with severe coronavirus disease 2019 (COVID-19) using radioligand assay (RLA). One thousand samples from the staff of a general hospital providing treatment to patients with severe COVID-19 were assayed for SARS-CoV-2 nucleocapsid protein (N) IgG using RLA. Nine patients with COVID-19 who had been treated in inpatient settings and had already recovered were used as control subjects, and 186 blood donor samples obtained more than 10 years ago were used as negative controls. Four of the 1000 samples showed apparently positive results, and approximately 10 or more samples showed slightly high counts. Interestingly, a few among the blood donor samples also showed slightly high values. To validate the results, antibody examinations using ELISA and neutralizing antibody tests were performed on 21 samples, and chemiluminescence immunoassay (CLIA) was performed on 201 samples, both resulting in a very high correlation. One blood donor sample showed slightly positive results in both RLA and CLIA, suggesting a cross-reaction. This study showed that five months after the pandemic began in Japan, the staff of a general hospital with a tertiary emergency medical facility had an extremely low seroprevalence of the antibodies against SARS-CoV-2. Further investigation will be needed to determine whether the slightly high results were due to cross-reactions or a low titer of anti-SARS-CoV-2 antibodies. The quantitative RLA was considered sensitive enough to detect low titers of antibodies