Protein folding and unfolding are coupled to a range of biological phenomena, from the regulation of cellular activity to the onset of neurodegenerative diseases. Defining the nature of the conformations sampled in nonnative proteins is crucial for understanding the origins of such phenomena. We have used a combination of nuclear magnetic resonance (NMR) spectroscopy and site-directed mutagenesis to study unfolded states of the protein lysozyme. Extensive clusters of hydrophobic structure exist within the wild-type protein even under strongly denaturing conditions. These clusters involve distinct regions of the sequence but are all disrupted by a single point mutation that replaced residue Trp62 with Gly located at the interface of the two major structural domains in the native state. Thus, nativelike structure in the denatured protein is stabilized by the involvement of Trp62 in nonnative and long-range interactions.

BackgroundThe Great East Japan Earthquake occurred at 2:46 p.m. on March 11, 2011. The epicenter was off the coast of Miyagi prefecture, and the magnitude of the earthquake was 9.0 with a maximum seismic intensity of 7.0. Although it has already been four years, victims continue to have complex problems. In the stricken areas of Miyagi prefecture, almost ten percent of the residents continue to live in temporary housing. Life altering events that force relocation and a change of living environment are known to adversely affect mental health. The purpose of this study was to examine the mental health of mothers of infants who experienced this disaster in Miyagi prefecture.MethodsWe conducted a survey using The Edinburgh Postnatal Depression Scale (10 months) and The General Health Questionnaire-28, an efficient screening tool for psychiatric distress. Eight hundred eighty-six mothers of children born from February to October, 2011 in Miyagi prefecture were surveyed 10, 16, 24, 36 and 48 months after the disaster. Data were analyzed with the use of SPSS 21.0 J for Windows. The study was approval by the review board of ethics at Tohoku University.ResultsThe questionnaire was answered by the following number of mothers at the specified months after the disaster: 677 at 10 months, 384 at 16 months, 351 at 24 months, 250 at 36 months and 193 at 48 months. Results at all time periods indicated a high prevalence of psychiatric distress among the mothers surveyed. The percentage of Japanese adults with high-risk GHQ-28 scores is 14 %, thus psychological distress among the subjects in the present study is considerably more widespread. General Health Questionnaire-28 scores were significantly higher for those mothers experiencing dissatisfaction in their marital relationships. We found that mothers have experienced severe mental distress since the disaster, which we think is a possible cause of depression that is leading to poor mental health.ConclusionThe results indicate that the upheaval caused by the tsunami affected the mental health of the mothers. Psychological distress continued to be prevalent up to four years after the disaster. Different factors were found to be associated with their distress. The most common issues were economic problems, dissatisfaction in the marital relationship, and no support with childcare.