Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.

G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology

Data-collection strategy for challenging native SAD phasing

Recent improvements in data-collection strategies have pushed the limits of native SAD (single-wavelength anomalous diffraction) phasing, a method that uses the weak anomalous signal of light elements naturally present in macromolecules. These involve the merging of multiple data sets from either multiple crystals or from a single crystal collected in multiple orientations at a low X-ray dose. Both approaches yield data of high multiplicity while minimizing radiation damage and systematic error, thus ensuring accurate measurements of the anomalous differences. Here, the combined use of these two strategies is described to solve cases of native SAD phasing that were particular challenges: the integral membrane diacylglycerol kinase (DgkA) with a low Bijvoet ratio of 1% and the large 200 kDa complex of the CRISPR-associated endonuclease (Cas9) bound to guide RNA and target DNA crystallized in the low-symmetry space group C2. The optimal native SAD data-collection strategy based on systematic measurements performed on the 266 kDa multiprotein/multiligand tubulin complex is discussed

Smoking, leisure-time exercise and frequency of self-reported common cold among the general population in northeastern China: a cross-sectional study

Abstract Background Physical activity (PA) and smoking have been reported to be associated with the duration and severity of common cold symptoms. However, few studies have addressed the associations between the frequency of leisure-time exercise, cigarette smoking status and the frequency of the common cold in a cold area. This study was designed to investigate these issues in northeastern China. Methods This cross-sectional study included individuals who participated in a regular health examination conducted in Jilin Province, China. Information on episodes of the common cold, the frequency of leisure-time exercise and cigarette smoking status in the past year were collected by self-administered health questionnaires. Ordinal logistic regression models were used to analyse the associations between the frequency of leisure-time exercise, cigarette smoking status and the retrospective frequency of common cold. Results A total of 1413 employees participated in the study, with an average age of 38.92 ± 9.04 years and 44.4% of them were male. Of all participants, 80.8% reported having experienced the common cold in the past year. After adjustment, the risk of suffering from the common cold more than once (odds ratios (ORs), 1.59; 95% confidence interval (CI), 1.27–1.99) in passive smokers was 1.59 times as high as that in non-smokers. Nevertheless, the results of the adjusted analysis showed no statistically significant relation between current smoking and the frequency of the common cold. A high frequency of leisure-time exercise (≥3 days/week) was associated with a 26% reduced risk of having at least one episode of the common cold (OR, 0.74; 95% CI, 0.55–0.98) compared with a low frequency group (< 4 days/month). For current and passive smokers, the protective effect of a high frequency of leisure-time exercise appears not to be obvious (current smokers: OR, 0.68; 95% CI, 0.33–1.43; passive smokers: OR, 1.15; 95% CI, 0.69–1.93). Conclusion Passive smoking was associated with a higher risk of having self-reported common cold at least once, while a high frequency of leisure-time exercise was related to a lower risk of reporting more than one episode of the disease in Chinese

Gender-specific association of metabolic syndrome and its components with arterial stiffness in the general Chinese population

<div><p>Objectives</p><p>Metabolic syndrome (MS) is considered to be a cluster of interrelated risk factors for metabolism, which may increase arterial stiffness and cardiovascular morbidity. The cardio-ankle vascular index (CAVI) is a reliable indicator of arterial stiffness and early arteriosclerosis. The main objective of this study is to evaluate the gender-specific relationship between MS and CAVI in the general Chinese population.</p><p>Methods</p><p>A total of 1,301 subjects aged 20 to 60 years participated in this study. CAVI was measured noninvasively using a Vasera VS-1000 device. Blood samples and waist circumference were examined to identify metabolic syndrome according to the criteria set forth in the 2009 Joint Scientific Statement.</p><p>Results</p><p>The prevalence of MS in the study subjects was 17.4% (30.7% in males and 7.0% in females, P < 0.001). CAVI values were significantly higher in MS subjects than in non-MS subjects and increased linearly as the number of MS components increased in females, but not in males. Using multiple regression analysis, we found that BMI was correlated with CAVI in the overall population and in both genders, and that high-density lipoprotein cholesterol (HDL-C) was associated with CAVI in males, while the number of MS components was related to CAVI in females. CAVI values increased linearly with age in both genders (P-trend < 0.001 for both), and this correlation was stronger in males than in females.</p><p>Conclusions</p><p>There are gender-specific differences in the association of MS and CAVI. First, the effects of the number of MS components on CAVI are stronger in females than in males. Second, the effect of each MS component on arterial stiffness may differ in relation to gender. In addition, aging affects arterial stiffness more severely in males, and the increase in arterial stiffness tends to occur at a younger age in males than in females. Larger samples and longitudinal studies are needed to further confirm our results in the future.</p></div

Trend test of CAVI values with the number of MS components in males and females.

<p>The solid lines show the differences between the groups in males, and the dotted line is the trendline for females. * <i>P</i> < 0.05 in males.</p

Characteristics of subjects stratified by sex and the presence/absence of metabolic syndrome.

<p>Characteristics of subjects stratified by sex and the presence/absence of metabolic syndrome.</p

The association between BMI and body weight perception among children and adolescents in Jilin City, China

<div><p>Objectives</p><p>We evaluated the association between BMI and body weight perception in a sample of children and adolescents.</p><p>Methods</p><p>A cross-sectional school-based study was conducted among 7–18 year-olds (N = 9727) from 4 districts in Jilin City, China. We calculated BMI from measured weight and height and assessed body weight perception using a single questionnaire item. We analyzed these data using SPSS version 20.0.</p><p>Results</p><p>Approximately 19.8% of these youth perceived themselves as underweight, 57.8% as normal weight, and 22.4% as overweight. In reality, 4.9% were underweight, 64.3% were normal weight, and 30.8% were overweight. Furthermore, approximately 66.4% of these Chinese youth correctly perceived their body image, 28.2% underestimated their true body image, and 5.4% overestimated their weight status. Girls were more likely than boys to overestimate their weight (<i>χ</i>^<i>2</i> = 135.4, p < 0.05). Adolescents 13–18 years old were more likely than children 7–12 years old to overestimate their weight (<i>χ</i>^<i>2</i> = 248.4, p < 0.05). Senior high school students were the most likely to overestimate their weight (<i>χ</i>^<i>2</i> = 297.6, p < 0.05). Kappa tests revealed significant differences in consistency analysis of BMI and body weight perception (<i>Kappa</i> = 0.352, p < 0.05). <i>Kappa</i> < 0.4, the consistency of BMI and body weight perception was poor.</p><p>Conclusions</p><p>A mismatch existed between BMI and body weight perception among these children and adolescents. Thus, schools and parents should take steps to help them improve weight management and overall health awareness.</p></div

Trend test of CAVI values with age in males and females.

<p>The solid line is the trendline for males, and the dotted line is the trendline for female.</p

Baseline characteristics of subjects.

<p>Baseline characteristics of subjects.</p