Effects of the Higashi-Nihon Earthquake: Posttraumatic Stress, Psychological Changes, and Cortisol Levels of Survivors

On March 11, 2011, the Pacific side of Japan’s northeast was devastated by an earthquake and tsunami. For years, many researchers have been working on ways of examining the psychological effects of earthquakes on survivors in disaster areas who have experienced aftershocks, catastrophic fires, and other damage caused by the earthquake. The goal of this study is to examine scores on psychological measures and salivary cortisol level in these individuals both before and three months after the earthquake. The participants had been measured for these variables before the earthquake. After the earthquake, we carried out PTSD screening using CAPS for participants for another experiment, and then again conducted the aforementioned tests. We collected saliva samples from all survivors. Our results show that social relationship scores on the WHO-QOL26, negative mood scores of the WHO-SUBI, total GHQ score, POMS confusion scores, and CMI emotional status score after the earthquake showed scores indicating significantly decreased compared to before the earthquake. On the other hand, salivary cortisol levels after the earthquake was significantly increased compared to before the earthquake. Moreover, the result of a multiple regression analysis found that negative mood score on the WHO-SUBI and social relationship score on the WHO-QOL26 were significantly related to salivary cortisol levels. Our results thus demonstrate that several psychological stress induced by the earthquake was associated with an increase in salivary cortisol levels. These results show similar findings to previous study. We anticipate that this study will provide a better understanding of posttraumatic responses in the early stages of adaptation to the trauma and expand effective prevention strategies and countermeasures for PTSD

Unexpected binding mode for 2 '-phosphoadenosine-based nucleotide inhibitors in complex with human angiogenin revealed by heteronuclear NMR spectroscopy

200343NRC publication: Ye

Unexpected binding mode for 2 '-phosphoadenosine-based nucleotide inhibitors in complex with human angiogenin revealed by heteronuclear NMR spectroscopy

200343NRC publication: Ye

Unexpected binding mode for 2′-phosphoadenosine-based nucleotide inhibitors in complex with human angiogenin revealed by heteronuclear NMR spectroscopy

Human angiogenin (Ang) is a tumor-promoting RNase in the pancreatic RNase superfamily. Efforts to develop nucleotide-based inhibitors of Ang as potential anticancer drugs have been hampered by the lack of direct structural information on Ang-nucleotide complexes. Here, we have used heteronuclear NMR spectroscopy with 15N- and 15N/13C-labeled Ang to map the interactions of Ang with the phosphate ion, seven adenosine mononucleotides (the 2′-, 3′-, and 5′-monophosphates, the 2′,5′- and 3′,5′-diphosphates, the 5′-diphosphate, and the 2′-monophospho-5′-diphosphate), and the dinucleotide 2′-deoxyuridine 3′-pyrophosphate (P′ → 5′) adenosine-2′-phosphate (dUppA-2′-p). The 2′-phosphate based derivatives, which bind more tightly than the corresponding 3′-phosphate isomers, induced characteristic large resonance perturbations of the backbone amide proton of Leu115, the backbone 15N of His 114, and the Gln12 side-chain NH2 group in the Ang active site. In contrast, adenosine derivatives with only 3′- or 5′-phosphates produced much less dramatic perturbations of Leu 115 and His114 resonances, along with modest perturbations of additional residues both within and beyond the active site. Measurements of NOEs together with molecular docking analyses revealed the three-dimensional structures of the complexes of Ang with adenosine 2′,5′-diphosphate and dUppA-2′-p; the binding modes of these inhibitors differ substantially from those predicted in earlier studies. Most notably, the 2′-phosphate rather than the 5′-phosphate occupies the P1 catalytic subsite of Ang, and the side chain of His114 has undergone a conformational transition that positions it outside P 1 and allows it to form stacking interactions with the adenine ring of the inhibitor. Strikingly, the 2′-deoxyuridine moiety of dUppA-2′-p makes only a few contacts with Ang, and these involve residues outside the B1 subsite where the pyrimidine ring of substrates normally binds