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

The synergistic cooperation of NH⋯O and CH⋯O hydrogen bonds in the structures of three new phosphoric triamides

<p>The supramolecular assemblies of three new phosphoric triamides, {(C₆H₅CH₂)(CH₃)N}₂(4-CH₃-C₆H₄C(O)NH)P(O) (<b>1</b>), {(C₆H₁₁)(CH₃)N}₂(4-CH₃-C₆H₄C(O)NH)P(O) (<b>2</b>) and {(C₂H₅)₂N}₂(4-CH₃-C₆H₄C(O)NH)P(O) (<b>3</b>) were studied by single crystal X-ray diffraction as well as by Hirshfeld surface analysis. It was found that a synergistic cooperation of NH⋯O and CH⋯O hydrogen bonds occurs in all three structures, but forming unique supramolecular architectures individually. Along with the presence of centrosymmetric dimers in <b>1, 2</b> and <b>3</b>, based on a classical NH⋯O hydrogen bond, the presence of weak CH⋯O interactions play an additional and vital role in crystal architecture and construction of the final assemblies, collectively identified as a centrosymmetric dimer (0D), a 1-D array and a 3-D network, respectively. These differences in superstructures are related to the effect of aromatic, bulk and flexible groups used in the molecules designed, with a similar C(O)NHP(O) backbone. The NH⋯O contacts in <b>1, 2</b> and <b>3</b> are of the “resonance-assisted hydrogen bond” types and also the <i>anti</i>-cooperativity effect can be considered in the multi-acceptor sites P═O in <b>1</b> and <b>2</b> and C═O in <b>3</b>. All three compounds were further studied by 1D NMR experiments, 2D NMR techniques (HMQC and HMBC (H–C correlation)), high resolution ESI–MS, EI–MS spectrometry and IR spectroscopy methods.</p

Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study

Objective To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease. Design Registry based observational study. Setting 74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021 Participants All adults (aged ≥18 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11 167 patients). Main outcome measures Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with ≥20 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease. Results Of 11 167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07). Conclusions In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research

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

Total, dietary, and supplemental calcium intake and mortality from all-causes, cardiovascular disease, and cancer: A meta-analysis of observational studies

Aims: This systematic review and meta-analysis of observational studies was conducted to summarize the evidence on the association between calcium intake and mortality. Methods and results: PubMed, Institute for Scientific Information (ISI) (Web of Science), SCOPUS, SciRUS, Google Scholar, and Excerpta Medica dataBASE (EMBASE) were searched to identify related articles published through May 2014. We found 22 articles that assessed the association between total, dietary, and supplementary intake with mortality from all-causes, cardiovascular disease (CVD), and cancer. Findings from this meta-analysis revealed no significant association between total and dietary calcium intake and mortality from all-causes, CVD, and cancer. Subgroup analysis by the duration of follow-up revealed a significant positive association between total calcium intake and CVD mortality for cohort studies with a mean follow-up duration of >10 years (relative risk (RR): 1.35; 95 confidence interval (CI): 1.09-1.68). A significant inverse association was seen between dietary calcium intake and all-cause (RR: 0.84; 95 CI: 0.70-1.00) and CVD mortality (RR: 0.88; 95 CI: 0.78-0.99) for studies with a mean follow-up duration of �10 years. Although supplemental calcium intake was not associated with CVD (RR: 0.95; 95 CI: 0.82-1.10) and cancer mortality (RR: 1.22; 95 CI: 0.81-1.84), it was inversely associated with the risk of all-cause mortality (RR: 0.91; 95 CI: 0.88-0.94). Conclusions: We found a significant relationship between the total calcium intake and an increased risk of CVD mortality for studies with a long follow-up time and a significant protective association between dietary calcium intake and all-cause and CVD mortality for studies with a mean follow-up of �10 years. Supplemental calcium intake was associated with a decreased risk of all-cause mortality. © 2015 Elsevier B.V

Patterns of dietary habits in relation to obesity in Iranian adults

Purpose: Findings from few studies that investigated the relation between dietary behaviors and obesity are inconsistent. We aimed to assess the relation between patterns of dietary habits, identified by latent class analysis (LCA), and obesity in a large sample of Iranian adults. Methods: In a cross-sectional study on 7958 adults, dietary behaviors were assessed in five domains (meal patterns, eating rate, intra-meal fluid intake, meal-to-sleep interval, and fatty foods intake) using a pretested questionnaire. LCA was applied to identify classes of diet-related practices. Anthropometric measures were assessed through the use of a validated self-reported questionnaire. General and abdominal obesity were defined as a body mass index ≥ 30 kg/m², and a waist circumference ≥ 88 cm for women and ≥ 102 cm for men. Results: General and abdominal obesity were prevalent in 9.7 and 27.7 % of the study population, respectively. We identified three distinct classes of eating rates (moderate, moderate to slow, and moderate to fast), two classes of meal patterns (regular and irregular), two classes of intra-meal fluid intake (moderate and more intra-meal drinking), three classes of meal-to-sleep interval (short, moderate, and long meal-to-sleep interval), and three classes of fatty food intake (low to moderate, moderate to high, and low intake of fatty foods). After adjustment for potential confounders, individuals with 'irregular meal pattern' were 21, 24, and 22 % more likely to be overweight/obese, abdominally overweight/obese, and abdominally obese, compared with those who had a 'regular meal pattern.' Individuals with 'more intra-meal drinking' had greater odds of overweight (OR 1.37; 1.19-1.458) and obesity (OR 1.51; 1.16-1.97) than those with 'moderate intra-meal drinking.' Moderate-to-high intake of fatty foods was inversely associated with abdominally overweight/obese (OR 0.85; 0.73-1.00) and abdominally obesity (OR 0.80; 0.68-0.96) compared with 'low-to-moderate intake of fatty foods.' No significant association was observed between eating rate, meal-to-sleep interval, and general or abdominal obesity, after controlling for confounders. Conclusion: Irregular meal pattern and more intra-meal drinking were associated with increased odds of general and abdominal obesity, whereas moderate-to-high intake of fatty foods was related to the decreased odds of central obesity among Iranian adults.Parvane Saneei, Ahmad Esmaillzadeh, Ammar Hassanzadeh Keshteli, Awat Feizi, Christine Feinle-Bisset, Peyman Adib