The effects of short-term calorie restriction on mutations in the spleen cells of infant-irradiated mice.

The risk of cancer due to exposure to ionizing radiation is higher in infants than in adults. In a previous study, the effect of adult-onset calorie restriction (CR) on carcinogenesis in mice after early-life exposure to X-rays was examined (Shang, Y, Kakinuma, S, Yamauchi, K, et al. Cancer prevention by adult-onset calorie restriction after infant exposure to ionizing radiation in B6C3F1 male mice. Int J Cancer. 2014; 135: 1038-47). The results showed that the tumor frequency was reduced in the CR group. However, the mechanism of tumor suppression by CR is not yet clear. In this study, we examined the effects of CR on radiation-induced mutations using gpt delta mice, which are useful to analyze mutations in various tissues throughout the whole body. Infant male mice (1-week old) were exposed to 3.8 Gy X-rays and fed a control (95 kcal/week/mouse) or CR (65 kcal/week/mouse) diet from adult stage (7-weeks old). Mice were sacrificed at the age of 7 weeks, 8 weeks and 100 days, and organs (spleen, liver, lung, thymus) were harvested. Mutations at the gpt gene in the DNA from the spleen were analyzed by using a gpt assay protocol that detects primarily point mutations in the gpt gene. The results showed that mutation frequencies were decreased in CR groups compared with non-CR groups. Sequence analysis of the gpt gene in mutants revealed a reduction in the G:C to T:A transversion in CR groups. Since it is known that 8-oxoguanine could result in this base substitution and that CR has an effect of reducing oxidative stress, these results indicate that the suppression of oxidative stress by CR is the cause of the reduction of this transversion

Physicochemical Characterization of the Catalytic Unit of Hammerhead Ribozyme and Its Relationship with the Catalytic Activity

The catalytic mechanism of hammerhead ribozymes (HHRzs) attracted great attention in relation to the chemical origin of life. However, the basicity (pKa) of the catalytic sites of HHRzs has not been studied so far. As a result, the investigation of the currently assumed mechanism from an experimentally derived pKa value has been impossible. In HHRzs, there exists a highly functionalized structural unit (A9-G10.1 site) with a catalytic residue (G12) for the nucleophile activation and metal ion-binding residue (G10.1). As inferred from this fact, there might be a possibility that HHRzs may utilize specific functions of the A9-G10.1 motif for the catalytic reaction. Therefore, here we studied the basicity of G12/G10.1-corresponding residues using RNA duplexes including the A9-G10.1 motif without other conserved residues of HHRzs. From the pH-titration experiments with NMR spectra, we have obtained the intrinsic basicity of the G12/G10.1-corresponding residues in the motif, with pKa > 11.5 (N1 of G12) and pKa 4.5 (N7 of G10.1) for the first time. Based on the derived irregular basicity, their correlation with a catalytic activity and a metal affinity were investigated. In total, the derived thermodynamic properties are an intrinsic nature of the exclusive catalytic unit of HHRzs, which will be an outstanding pivot point for the mechanistic analyses

Physicochemical Characterization of the Catalytic Unit of Hammerhead Ribozyme and Its Relationship with the Catalytic Activity

The catalytic mechanism of hammerhead ribozymes (HHRzs) attracted great attention in relation to the chemical origin of life. However, the basicity (pKa) of the catalytic sites of HHRzs has not been studied so far. As a result, the investigation of the currently assumed mechanism from an experimentally derived pKa value has been impossible. In HHRzs, there exists a highly functionalized structural unit (A9-G10.1 site) with a catalytic residue (G12) for the nucleophile activation and metal ion-binding residue (G10.1). As inferred from this fact, there might be a possibility that HHRzs may utilize specific functions of the A9-G10.1 motif for the catalytic reaction. Therefore, here we studied the basicity of G12/G10.1-corresponding residues using RNA duplexes including the A9-G10.1 motif without other conserved residues of HHRzs. From the pH-titration experiments with NMR spectra, we have obtained the intrinsic basicity of the G12/G10.1-corresponding residues in the motif, with pKa > 11.5 (N1 of G12) and pKa 4.5 (N7 of G10.1) for the first time. Based on the derived irregular basicity, their correlation with a catalytic activity and a metal affinity were investigated. In total, the derived thermodynamic properties are an intrinsic nature of the exclusive catalytic unit of HHRzs, which will be an outstanding pivot point for the mechanistic analyses

Have the tsunami and nuclear accident following the Great East Japan Earthquake affected the local distribution of hospital physicians?

Objective: The Great East Japan Earthquake occurred on 11 March 2011 near the northeast coast of the main island, ‘Honshu’, of Japan. It wreaked enormous damage in two main ways: a giant tsunami and an accident at the Fukushima Daiichi Nuclear Power Plant (FDNPP). This disaster may have affected the distribution of physicians in the region. Here, we evaluate the effect of the disaster on the distribution of hospital physicians in the three most severely affected prefectures (Iwate, Miyagi, and Fukushima). Methods: We obtained individual information about physicians from the Physician Census in 2010 (pre-disaster) and 2012 (post-disaster). We examined geographical distributions of physicians in two ways: (1) municipality-based analysis for demographic evaluation; and (2) hospital-based analysis for geographic evaluation. In each analysis, we calculated the rate of change in physician distributions between pre- and post-disaster years at various distances from the tsunami-affected coast, and from the restricted area due to the FDNPP accident. Results: The change in all, hospital, and clinic physicians were 0.2%, 0.7%, and −0.7%, respectively. In the municipality-based analysis, after taking account of the decreased population, physician numbers only decreased within the restricted area. In the hospital-based analysis, hospital physician numbers did not decrease at any distance from the tsunami-affected coast. In contrast, there was a 3.3% and 2.3% decrease in hospital physicians 0–25 km and 25–50 km from the restricted area surrounding the FDNPP, respectively. Additionally, decreases were larger and increases were smaller in areas close to the FDNPP than in areas further away. Conclusions: Our results suggest that the tsunami did not affect the distribution of physicians in the affected regions. However, the FDNPP accident changed physician distribution in areas close to the power plant.This research was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number JP25516015 (http://www.jsps.go.jp/english/e-grants/index.html). The founder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript