The structure of a tetrameric α-carbonic anhydrase from Thermovibrio ammonificans reveals a core formed around intermolecular disulfides that contribute to its thermostability

Carbonic anhydrase enzymes catalyse the reversible hydration of carbon dioxide to bicarbonate. A thermophilic Thermovibrio ammonificans α-carbonic anhydrase (TaCA) has been expressed in Escherichia coli and structurally and biochemically characterized. The crystal structure of TaCA has been determined in its native form and in two complexes with bound inhibitors. The tetrameric enzyme is stabilized by a unique core in the centre of the molecule formed by two intersubunit disulfides and a single lysine residue from each monomer that is involved in intersubunit ionic interactions. The structure of this core protects the intersubunit disulfides from reduction, whereas the conserved intrasubunit disulfides are not formed in the reducing environment of the E. coli host cytosol. When oxidized to mimic the environment of the periplasmic space, TaCA has increased thermostability, retaining 90% activity after incubation at 70°C for 1 h, making it a good candidate for industrial carbon-dioxide capture. The reduction of all TaCA cysteines resulted in dissociation of the tetrameric molecule into monomers with lower activity and reduced thermostability. Unlike other characterized α-carbonic anhydrases, TaCA does not display esterase activity towards p-nitrophenyl acetate, which appears to result from the increased rigidity of its protein scaffold.Statoil ASAUniversity of ExeterBotechnology and Biological Sciences Research Council (BBSRC)Wellcome TrustEUEngineering and Physical Sciences Research Council (EPSRC

New Thermophilic α/β Class Epoxide Hydrolases Found in Metagenomes From Hot Environments

This is the final version. Available from Frontiers Media via the DOI in this record.Two novel epoxide hydrolases (EHs), Sibe-EH and CH65-EH, were identified in the metagenomes of samples collected in hot springs in Russia and China, respectively. The two α/β hydrolase superfamily fold enzymes were cloned, over-expressed in Escherichia coli, purified and characterized. The new EHs were active toward a broad range of substrates, and in particular, Sibe-EH was excellent in the desymmetrization of cis-2,3-epoxybutane producing the (2R,3R)-diol product with ee exceeding 99%. Interestingly these enzymes also hydrolyse (4R)-limonene-1,2-epoxide with Sibe-EH being specific for the trans isomer. The Sibe-EH is a monomer in solution whereas the CH65-EH is a dimer. Both enzymes showed high melting temperatures with the CH65-EH being the highest at 85°C retaining 80% of its initial activity after 3 h thermal treatment at 70°C making it the most thermal tolerant wild type epoxide hydrolase described. The Sibe-EH and CH65-EH have been crystallized and their structures determined to high resolution, 1.6 and 1.4 Å, respectively. The CH65-EH enzyme forms a dimer via its cap domains with different relative orientation of the monomers compared to previously described EHs. The entrance to the active site cavity is located in a different position in CH65-EH and Sibe-EH in relation to other known bacterial and mammalian EHs

Healthy dietary indices and risk of depressive outcomes : a systematic review and meta-analysis of observational studies

With depression being the psychiatric disorder incurring the largest societal costs in developed countries, there is a need to gather evidence on the role of nutrition in depression, to help develop recommendations and guide future psychiatric health care. The aim of this systematic review was to synthesize the link between diet quality, measured using a range of predefined indices, and depressive outcomes. Medline, Embase and PsychInfo were searched up to 31st May 2018 for studies that examined adherence to a healthy diet in relation to depressive symptoms or clinical depression. Where possible, estimates were pooled using random effect meta-analysis with stratification by observational study design and dietary score. A total of 20 longitudinal and 21 cross-sectional studies were included. These studies utilized an array of dietary measures, including: different measures of adherence to the Mediterranean diet, the Healthy Eating Index (HEI) and Alternative HEI (AHEI), the Dietary Approaches to Stop Hypertension, and the Dietary Inflammatory Index. The most compelling evidence was found for the Mediterranean diet and incident depression, with a combined relative risk estimate of highest vs. lowest adherence category from four longitudinal studies of 0.67 (95% CI 0.55-0.82). A lower Dietary Inflammatory Index was also associated with lower depression incidence in four longitudinal studies (relative risk 0.76; 95% CI: 0.63-0.92). There were fewer longitudinal studies using other indices, but they and cross-sectional evidence also suggest an inverse association between healthy diet and depression (e.g., relative risk 0.65; 95% CI 0.50-0.84 for HEI/AHEI). To conclude, adhering to a healthy diet, in particular a traditional Mediterranean diet, or avoiding a pro-inflammatory diet appears to confer some protection against depression in observational studies. This provides a reasonable evidence base to assess the role of dietary interventions to prevent depression.Peer reviewe

Effect of individualised dietary advice for weight loss supplemented with walnuts on blood pressure: the HealthTrack study

Background/objectives: In addition to weight-loss, healthy dietary patterns and lower sodium intakes can help reduce blood pressure (BP), but individualised dietary advice may be necessary to achieve these effects. This study aimed to examine the impact of individualised dietary advice on BP in the intensive phase of a weight-loss trial. Subjects/methods: Secondary analysis of baseline and 3-month data from the HealthTrack randomised controlled trial (n = 211). Participants were randomly assigned to one of three dietary advice groups: general advice (control), individualised advice (intervention group, I), or intervention group supplemented with 30 g walnuts/day (IW). Resting BP and 24-h urine sodium and potassium were measured. Dietary intake was evaluated through diet history interviews. Results: Unadjusted SBP reduced significantly in all groups (IW and I groups P \u3c 0.001; control group P = 0.002) and DBP in IW and I groups (P \u3c 0.001). Compared to controls, the reductions in BP were 3-4 mmHg greater in the I and IW groups, but this only reached significance for DBP in the I group (−3.3 mmHg; P = 0.041). After controlling for age, sex, medication, weight-loss, physical activity and smoking, only the IW group showed a significant association between SBP reduction and increased urinary potassium (β = −0.101, P = 0.044), decreased sodium:potassium ratio (β = 2.446, P = 0.037) and increased consumption of seed and nut products and dishes (β = −0.108, P = 0.034). Conclusions: Dietary patterns with distinctive foods and lower sodium:potassium ratios may enhance the effects of weight-loss on BP. The patterns were best achieved with individualised dietary advice and food supplements

Real life management of chronic urticaria: Multicenter and cross sectional study on patients and dermatologists in Iran

Recently, advances in understanding the etiology of urticaria and updates of diagnostic and therapeutic management guidelines have drawn attention to chronic urticaria (CU) morbidity. The present study aimed to evaluate Iranian dermatologists' practice and real life management of CU patients. A total of 35 dermatologists and 443 patients were included in the study. Number of female patients was 321 (72.5). Mean (standard deviation) age of the study patients was 38 (13) years and the median (inter quartile range) of disease duration was 12 (6�48) months. Severity of patients' symptoms was mild for 32.1, moderate for 38.7, severe for 18.8, and 10.4 of them had no evident signs or symptoms. The most common diagnostic methods were physical examination (96.6), differential blood count (83.5), erythrocyte sedimentation rate (77.4), and C-reactive protein (62.8). The number of dermatologists prescribed nonsedating antihistamines (nsAH) in regular dose and high dose mono therapy were 26 (74) and 6 (17), respectively. About 66 of dermatologists were familiar with British Association of Dermatologists (BAD) guideline. The most common first-line treatment for CU by Iranian dermatologists was nonsedating antihistamines in regular or high doses. The real-life management of patients with CU in Iran was in accordance with the available practice guidelines. © 2018 Wiley Periodicals, Inc