Quantum Mechanics/Molecular Mechanics Study of Resting-State Vanadium Nitrogenase: Molecular and Electronic Structure of the Iron–Vanadium Cofactor

Publisher's version (útgefin grein)The nitrogenase enzymes are responsible for all biological nitrogen reduction. How this is accomplished at the atomic level, however, has still not been established. The molybdenum-dependent nitrogenase has been extensively studied and is the most active catalyst for dinitrogen reduction of the nitrogenase enzymes. The vanadium-dependent form, on the other hand, displays different reactivity, being capable of CO and CO2 reduction to hydrocarbons. Only recently did a crystal structure of the VFe protein of vanadium nitrogenase become available, paving the way for detailed theoretical studies of the iron-vanadium cofactor (FeVco) within the protein matrix. The crystal structure revealed a bridging 4-atom ligand between two Fe atoms, proposed to be either a CO32- or NO3- ligand. Using a quantum mechanics/molecular mechanics model of the VFe protein, starting from the 1.35 Å crystal structure, we have systematically explored multiple computational models for FeVco, considering either a CO32- or NO3- ligand, three different redox states, and multiple broken-symmetry states. We find that only a [VFe7S8C(CO3)]2- model for FeVco reproduces the crystal structure of FeVco well, as seen in a comparison of the Fe-Fe and V-Fe distances in the computed models. Furthermore, a broken-symmetry solution with Fe2, Fe3, and Fe5 spin-down (BS7-235) is energetically preferred. The electronic structure of the [VFe7S8C(CO3)]2- BS7-235 model is compared to our [MoFe7S9C]- BS7-235 model of FeMoco via localized orbital analysis and is discussed in terms of local oxidation states and different degrees of delocalization. As previously found from Fe X-ray absorption spectroscopy studies, the Fe part of FeVco is reduced compared to FeMoco, and the calculations reveal Fe5 as locally ferrous. This suggests resting-state FeVco to be analogous to an unprotonated E1 state of FeMoco. Furthermore, V-Fe interactions in FeVco are not as strong compared to Mo-Fe interactions in FeMoco. These clear differences in the electronic structures of otherwise similar cofactors suggest an explanation for distinct differences in reactivity.R.B. acknowledges support from the Icelandic Research Fund (Grants 141218051 and 162880051) and University of Iceland Research Fund. Open Access funding was provided by the Max Planck Society.Peer Reviewe

Oxide nanoparticle exsolution in Lu-doped (Ba,La)CoO3

This study investigated Lu doping of BaLaCoO and its influence on the exsolution of oxide nanoparticles (NPs). As a result of Lu doping, we observed the phase segregation into the main BaLaCoLuO (BLCO-Lu) phase and the secondary BaLaCoLuO (BCO-Lu) phase. We noticed the exsolution of BCO-Lu nanoparticles on the main BLCO-Lu phase. Moreover, the BLCO-Lu phase exsolved in the form of nanoparticles on the adjacent BCO-Lu grains. That shows that the phases are covered with mutually exsolved oxide NPs. In addition, trace amounts of the BaLuCoO phase are detected. We noticed that the exsolved oxides even in the as-prepared sample were fine (average size of 18 nm), and well distributed with a dense population of NPs above 280 per 1 μm. Furthermore, we showed that the size and shape of the exsolved oxide NPs can be controlled by varying the annealing temperature. For example, at 800 °C the exsolved oxides segregate and form two different shapes; spherical and cuboidal, with an average size of 31 nm and NP population of about 23 NPs per μm. Meanwhile, with lowering the temperature to 400 °C the oxides form only spherical and quite evenly distributed NPs with the occurrence of 137 NPs per 1 μm. The obtained results open the possibility of tailoring a novel, more catalytically active material for future applications in electrochemical devices.Project FunKeyCat is supported by the National Science Centre, Poland under the M-ERA.NET 2, which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement no 685451. The Research Council of Norway is also acknowledged for support to the Norwegian Center for Transmission Electron Microscopy (NORTEM) (no. 197405/F50)

Structural properties of mixed conductor Ba1−xGd1−yLax+yCo2O6−δ

BaGdLaCoO (BGLC) compositions with large compositional ranges of Ba, Gd, and La have been characterised with respect to phase compositions, structure, and thermal and chemical expansion. The results show a system with large compositional flexibility, enabling tuning of functional properties and thermal and chemical expansion. We show anisotropic chemical expansion and detailed refinements of emerging phases as La is substituted for Ba and Gd. The dominating phase is the double perovskite structure Pmmm, which is A-site ordered along the c-axes and with O vacancy ordering along the b-axis in the Ln-layer. Phases emerging when substituting La for Ba are orthorhombic Ba-deficient Pbnm and cubic LaCoO-based R3̄c. When La is almost completely substituted for Gd, the material can be stabilised in Pmmm, or cubic Pm3̄m, depending on thermal and atmospheric history. We list thermal expansion coefficients for x = 0-0.3, y = 0.2.The research has been supported by the National Science Centre Poland (2016/22/Z/ST5/00691), the Spanish Ministry of Science and Innovation (PCIN-2017-125, RTI2018-102161 and IJCI-2017-34110), and the Research Council of Norway (Grant no. 272797 “GoPHy MiCO”) through the M-ERA.NET Joint Call 2016. The authors acknowledge the skilful assistance from the staff of the Swiss–Norwegian Beamline (SNBL) at the European Synchrotron Radiation Facility (ESRF), Grenoble, France. Dr. Cheng Li at POWGEN, SNS, Oak Ridge, US and Dr. Chiu C. Tang at beamline I11 at Diamond, Didcot, UK are gratefully acknowledged for PND and SR-PXD measurements, respectively

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

Maternal position during the first stage of labor: a systematic review

BACKGROUND: Policy makers and health professionals are progressively using evidence-based rationale to guide their decisions. There has long been controversy regarding which maternal position is more appropriate during the first stage of labor. This problem has been examined often and repeatedly and the optimal recommendation remains unclear. METHODS: This is a systematic review of the effect of maternal position during the first stage of labor. The main question addressed here is: Does encouraging women to adopt an upright position or to ambulate during the first stage of labor reduce the duration of this stage? All randomized controlled trials carried out to assess this effect were taken into consideration in this review. The following electronic databases were accessed to identify studies: MEDLINE, Popline, the Scientific Electronic Library On-line and the Latin American and Caribbean Health Science Information. Citation eligibility was independently assessed by two reviewers. The methodological quality of each trial was also evaluated independently by two reviewers and a trial under consideration was included only when consensus had been attained. Allocation concealment and screening for the occurrence of attrition, performance and detection biases were considered when studies were appraised. The decision whether to perform data pooling was based on the clinical similarity of studies. RESULTS: The search strategy resulted in 260 citations, of which 18 were assessed in full-text. Nine eligible randomized controlled trials were included in the systematic review. Randomization methods were not fully described in eight studies. The allocation concealment was considered adequate in four studies and unclear in five. The investigators pooled the data from seven studies in which the length of the first stage of labor and results were in favor of the intervention, but the high level of heterogeneity (I(2 )= 88.4%) impaired the meaning of this finding. The intervention did not affect other outcomes studied (mode of delivery, use of analgesia, labor augmentation and condition of the child at birth). CONCLUSION: Adoption of the upright position or ambulation during first stage of labor may be safe, but considering the available evidence and its consistency, it cannot be recommended as an effective intervention to reduce duration of the first stage of labor

The structure of quality systems is important to the process and outcome, an empirical study of 386 hospital departments in Sweden

<p>Abstract</p> <p>Background</p> <p>Clinicians, nurses, and managers in hospitals are continuously confronted by new technologies and methods that require changes to working practice. Quality systems can help to manage change while maintaining a high quality of care. A new model of quality systems inspired by the works of Donabedian has three factors: structure (resources and administration), process (culture and professional co-operation), and outcome (competence development and goal achievement). The objectives of this study were to analyse whether structure, process, and outcome can be used to describe quality systems, to analyse whether these components are related, and to discuss implications.</p> <p>Methods</p> <p>A questionnaire was developed and sent to a random sample of 600 hospital departments in Sweden. The adjusted response rate was 75%. The data were analysed with confirmatory factor analysis and structural equation modeling in LISREL. This is to our knowledge the first large quantitative study that applies Donabedian's model to quality systems.</p> <p>Results</p> <p>The model with relationships between structure, process, and outcome was found to be a reasonable representation of quality systems at hospital departments (p = 0.095, indicating no significant differences between the model and the data set). Structure correlated strongly with process (0.72) and outcome (0.60). Given structure, process also correlated with outcome (0.20).</p> <p>Conclusion</p> <p>The model could be used to describe and evaluate single quality systems or to compare different quality systems. It could also be an aid to implement a systematic and evidence-based system for working with quality improvements in hospital departments.</p

Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations

A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 x 10(-7), 4.3 x 10(-9)) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.publishedVersio

The Dutch Disease in Reverse: Iceland's Natural Experiment

For a long time, abundant natural resources brought Iceland a high and volatile real exchange rate with adverse effects on manufacturing and services. During 2003-2008, another national treasure, the sovereign’s AAA rating, was used by privatized banks to attract foreign capital, elevating the real exchange rate even further. The financial collapse and the associated collapse of the currency in 2008 left the country with a large foreign debt which offset some of the effect of the natural resources on the real exchange rate. In effect, this was the Dutch disease in reverse as witnessed, in particular, by a massive increase in the number of tourists following the financial collapse. This paper discusses the behavior of the exchange rate of the Icelandic króna before and after 2008 as well as its relationship to natural resources, capital flows, output, exports and imports, including tourism