Homologous p35 proteins of baculoviruses show distinctive anti-apoptotic activities which correlate with the apoptosis-inducing activity of each virus1The last author, Professor Maeda, has passed away after the acceptance of the paper. The rest of the authors would like this paper to be a memorial to him.1

AbstractThe anti-apoptotic activity of p35s from two baculoviruses, Autographa californica nucleopolyhedrovirus (AcNPV) and Bombyx mori NPV (BmNPV), was compared in mammalian cells. AcNPV p35 efficiently blocked apoptosis induced by caspase overexpression, but BmNPV p35 did so very poorly. Analysis of chimeric p35s and in vitro cleavage of wild type p35s suggest that the cleavage efficiency of p35 correlates with the blocking activity. Single amino acid substitutions of BmNPV p35 with those observed in AcNPV p35, however, resulted in significant loss of its anti-apoptotic activity. We speculate that sequences flanking the cleavage site have uniquely evolved during baculovirus evolution

Psychological, social, and environmental factors to meeting physical activity recommendations among Japanese adults

<p>Abstract</p> <p>Background</p> <p>Although the benefits of the recommended level of physical activity on reducing chronic diseases are well-established, most of the Japanese population is not sufficiently active. Thus, examining correlates is an important prerequisite for designing relevant polices and effective programs. The present study investigated psychological, social, and environmental factors associated with meeting physical activity recommendations among Japanese adults.</p> <p>Methods</p> <p>Data were analyzed for 1,932 men and women (43.6 ± 13.0 years), who responded to an Internet-based cross-sectional survey. Self-reported measure of physical activity, psychological (self-efficacy, pros, and cons), social (social support, health professional advice), environmental (home fitness equipment, access to facilities, neighborhood safety, enjoyable scenery, frequently observing others exercising, residential area), and demographic (gender, age, marital status, educational level, household income level, employment status) variables were obtained. Based on the current national guidelines for exercise in Japan (23 METs·hour per week), respondents were divided into two categories–recommended and not recommended (insufficient and inactive)–according to their estimated weekly physical activity level. An adjusted logistic regression model was utilized.</p> <p>Results</p> <p>When adjusting for all other variables, self-efficacy (men: OR = 2.13; 95% CI: 1.55–2.94, women: OR = 2.72; 95% CI: 1.82–4.08) and possessing home fitness equipment (men: OR = 1.55; 95% CI: 1.14–2.10, women: OR = 1.41; 95% CI: 1.01–1.99) for both genders, social support (OR = 1.44; 95% CI: 1.06–1.97) for men, and enjoyable scenery (OR = 1.60; 95% CI: 1.09–2.36) for women were positively associated with attaining the recommended level of physical activity. In women, cons (OR = 0.47; 95% CI: 0.33–0.67) and living in rural areas (OR = 0.50; 95% CI: 0.25–0.97) were negatively associated with meeting the physical activity recommendations.</p> <p>Conclusion</p> <p>In the psychological, social, and environmental domains, significant correlates of attaining the recommended level of physical activity were observed. Men and women had different patterns of psychological, social, and environmental correlates. These findings suggest that an intervention design that accounts for those correlates may more effectively promote physical activity among Japanese adults.</p

新規トランスポーターマッピング剤による「アルツハイマー病の早期診断」に関する研究

金沢大学学際科学実験センターアルツハイマー病を核医学的手法により客観的に診断するには、アルツハイマー病の神経化学的変化等を鋭敏に控える放射性核種標識分子イメージング剤の開発が必要である。我々は以前より、アルツハイマー病で最も変化があるとされるアセチルコリン神経系に注目し、その中でもアセチルコリン神経シナプス前終末部に存在するアセチルコリントランスポーター(VAChT)の変化を画像化する分子イメージング剤の開発研究を進めてきた。また、シグマ受容体は学習/記憶メカニズムと密接に関係があるとされている。また、シグマ受容体は老齢化に伴い増加する傾向があり、シグマ受容体は老化による、精神神経的な異常に対して、正常に保とうと強く働いている可能性がある。したがって、シグマ受容体分子イメージングにより、アルツハイマー病を含む痴呆や種々の精神神経疾患の進行度(重症度)が把握できることが期待される。本研究では、アルツハイマー病の神経化学的変化等を鋭敏に捉える放射性核種標識分子イメージング剤の開発をめざし、PET用のポジトロン核種である炭素-11(11C)で標識したVAChT及びシグマ受容体分子イメージング剤の開発を検討した。まず、我々は、ベサミコール類がVAChTとシグマ受容体に高い親和性を有していることから、それぞれVAChTやシグマ受容体にのみ高い親和性を有するベサミコール類の合成を検討した。その結果、ポジトロン核種であるC-11の導入を容易にするため、ベサミコールのオルト位にメチル基を導入した(-)-ortho-imethylvesamicol((-)-oMeVES)とベサミコールのパラ位にメチル基を導入した(+)-para-methylvesamicol((+)-pMeVES)がそれぞれVAChTとシグマ受容体に選択的に高い親和性を有する化合物であることがわかった。合成はそれぞれ2-bromobenzaldehyde及び4-bromobenzaldehydeを出発原料として、同じ合成経路を経て、10行程で目的の(-)-oMeVES及び(+)-pMeVESが通算収率2-5%で合成できた。構造はNMR,質量分析、元素分析により確認した。(-)-oMeVESはVAChTに対してベサミコール(ki=4.4nM)と同様に高い親和性(Ki=6.7nM)を示した。また、(+)-pMeVESはシグマ受容体(σ-1)対して、高い親和性(σ-1(Ki=3.0nM),σ-2(Ki=40.7nM))を示した。以上のことから、メチル基を有する(-)oMeVESや(+)pMeVESはポジトロン核種であるC-11で容易に標識可能であり、それぞれPET用のVAChTやシグマ受容体分子イメージング剤のリガンドになると考えられた。We synthesized methylvesamicol analogs and investigated the binding characteristics of 2-[4-phenylpiperidino]cyclohexanol (vesamicol) and methylvesamicol analogs, with a methyl group introduced into the 4-phenylpiperidine moiety, to sigma receptors (σ-1, σ-2) and to vesicular acetylcholine transporters (VAChT) in membranes of the rat brain and liver. In competitive inhibition studies, (-)-o-methylvesamicol [(-)-oMeV] (Ki = 6.7 nM), as well as (-)-vesamicol (Ki = 4.4 nM) had a high affinity for VAChT. (+)-p-methylvesamicol [(+)-pMeV] (Ki = 3.0 nM), as well as SA4503 (Ki = 4.4 nM), reported as a σ-1 mapping agent for positron emission tomography (PET), had a high affinity for the σ-1 receptor. The binding affinity of (+)-pMeV for the σ-1 receptor (Ki = 3.0 nM), was about 13 times higher than the sigma-2 (σ-2) receptor (Ki = 40.7 nM). (+)-pMeV (Ki = 199 nM) had a much lower affinity for VAChT than SA4503 (Ki = 50.2 nM) and haloperidol (Ki = 41.4 nM). These results showed that the binding characteristics of (-)-oMeV (13) to VAChT were similar to that of (-)-vesamicol and, that (+)-pMeV (16) bound to the σ-1 receptor with high affinity. In conclusion, (-)-oMeV and (+)-pMeV(16), which had a suitable structure, with a methyl group for labeling with 11C, may become not only a new VAChT ligand and a new type of σ receptor ligand, respectively, but may also become a new target compound of VAChT and the σ-1 receptor radiolig and for positron emission tomography (PET), respectively.研究課題/領域番号:17591257, 研究期間(年度):2005 – 2006出典：「新規トランスポーターマッピング剤による「アルツハイマー病の早期診断」に関する研究」研究成果報告書　課題番号17591257（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/report/KAKENHI-PROJECT-17591257/175912572006kenkyu_seika_hokoku_gaiyo/)を加工して作

アルツハイマー性痴呆の診断を目的としたSPECT用標識薬剤の開発に関する研究

金沢大学助手研究課題/領域番号:03770685, 研究期間(年度):1991出典：研究課題「アルツハイマー性痴呆の診断を目的としたSPECT用標識薬剤の開発に関する研究」課題番号03770685（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-03770685/）を加工して作

^<14>C -標識神経伝達物質の合成並びに脳内代謝に関する研究

金沢大学医学部研究課題/領域番号:57770732, 研究期間(年度):1982出典：研究課題「^C -標識神経伝達物質の合成並びに脳内代謝に関する研究」課題番号57770732（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-57770732/）を加工して作

Improvement of resistance against hydrogen embrittlement by increasing carbon segregationat prior austenite grain boundary in low-carbon martensitic steels

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Improvement of resistance against hydrogen embrittlement by controlling carbon segregation at prior austenite grain boundary in 3Mn-0.2C martensitic steels

This study challenged to improve the resistance against hydrogen embrittlement by increasing the concentration of carbon segregated at prior austenite grain boundary (PAGB), XPAGB, in low-carbon martensitic steels. The specimens with/without carbon segregation treatment (Non-seg and Seg specimens, respectively) had almost the same microstructure, other than higher XPAGB in the Seg specimen. While the uncharged Non-seg and Seg specimens exhibited similar mechanical properties, the maximum stress of the hydrogen-charged specimen was much higher in the Seg specimen than that in the Non-seg specimen even when diffusible hydrogen contents were almost the same. In addition, the fraction of intergranular fracture surface was much smaller in the Seg specimen. Based on these results, we conclude that the segregated carbon suppressed the accumulation of hydrogen around PAGB by site competition and increased cohesive energy of PAGB, leading to the significantly improved resistance against hydrogen-related intergranular fracture

High-sensitivity quantitative analysis reveals the non-linear relationship between the dose and deposition of diphenylarsinic acid in the rat central nervous system following its subchronic exposure

In the year 2003, the residents of Kamisu, Japan, were exposed to pentavalent organic arsenic diphenylarsinic acid (DPAA[V]) via their normal drinking water. Following the exposure, they developed cerebellar and brainstem symptoms. Although the relatively high dose of DPAA(V) is assumed to have caused their symptoms, the relationship between the exposed dose of DPAA(V) and the level of their deposition in the central nervous system (CNS) remains unclear. Using liquid chromatography–tandem mass spectrometry, we examined the deposition of DPAA(V) and its pentavalent metabolites in the CNS tissues of Crl:CD(SD) rats following the administration of DPAA(V) for 28 days. We found that the concentrations of DPAA(V) in the CNS were very high, given a dose of 5.0 mg/kg/day. However, very low concentrations of DPAA(V) were detected at a dose of 0.3 or 1.2 mg/kg/day, suggesting the absence of a linear dose-response relationship between the dose and deposition of DPAA(V). We also found that this non-linear relationship was commonly observed in various non-CNS tissues, including the excretory system. Our study showed for the first time the exact relationship between the dose and tissue deposition of the organic arsenic following its subchronic administration

Change of Deformation Mechanisms Leading to High Strength and Large Ductility in Mg-Zn-Zr-Ca Alloy with Fully Recrystallized Ultrafine Grained Microstructures

Recently, we have found that fully recrystallized ultrafine-grained (UFG) microstructures could be realized in a commercial precipitation-hardened Magnesium (Mg) alloy. The UFG specimens exhibited high strength and large ductility under tensile test, but underlying mechanisms for good mechanical properties remained unclear. In this study, we have carried out systematic observations of deformation microstructures for revealing the influence of grain size on the change of dominant deformation modes. We found that plastic deformation of conventionally coarse-grained specimen was predominated by {0001} slip and {10–12} twinning, and the quick decrease of work-hardening rate was mainly due to the early saturation of deformation twins. For the UFG specimens, {10–12} twinning was dramatically suppressed, while non-basal slip systems containing component of Burgers vector were activated, which contributed significantly to the enhanced work-hardening rate leading to high strength and large ductility. It was clarified by this study that limited ductility of hexagonal Mg alloys could be overcome by activating unusual slip systems ( dislocations) in fully recrystallized UFG microstructures