The role of a disulfide bridge in the stability and folding kinetics of Arabidopsis thaliana cytochrome c6A

Cytochrome c 6A is a eukaryotic member of the Class I cytochrome c family possessing a high structural homology with photosynthetic cytochrome c 6 from cyanobacteria, but structurally and functionally distinct through the presence of a disulfide bond and a heme mid-point redox potential of + 71 mV (vs normal hydrogen electrode). The disulfide bond is part of a loop insertion peptide that forms a cap-like structure on top of the core α-helical fold. We have investigated the contribution of the disulfide bond to thermodynamic stability and (un)folding kinetics in cytochrome c 6A from Arabidopsis thaliana by making comparison with a photosynthetic cytochrome c 6 from Phormidium laminosum and through a mutant in which the Cys residues have been replaced with Ser residues (C67/73S). We find that the disulfide bond makes a significant contribution to overall stability in both the ferric and ferrous heme states. Both cytochromes c 6A and c 6 fold rapidly at neutral pH through an on-pathway intermediate. The unfolding rate for the C67/73S variant is significantly increased indicating that the formation of this region occurs late in the folding pathway. We conclude that the disulfide bridge in cytochrome c 6A acts as a conformational restraint in both the folding intermediate and native state of the protein and that it likely serves a structural rather than a previously proposed catalytic role. © 2011 Elsevier B.V. All rights reserved

Arc sensitivity to cluster ellipticity, asymmetries and substructures

We investigate how ellipticity, asymmetries and substructures separately affect the ability of galaxy clusters to produce strong lensing events, i.e. gravitational arcs, and how they influence the arc morphologies and fluxes. This is important for those studies aiming, for example, at constraining cosmological parameters from statistical lensing, or at determining the inner structure of galaxy clusters through gravitational arcs. We do so by creating two-dimensional gradually smoothed, differently elliptical and asymmetric versions of some numerical models. On average, we find that the contributions of ellipticity, asymmetries and substructures amount to ~40%, ~10% and ~30% of the total strong lensing cross section, respectively. However, our analysis shows that substructures play a more important role in less elliptical and asymmetric clusters, even if located at large distances from the cluster centers (~1Mpc/h). Conversely, their effect is less important in highly asymmetric lenses. The morphology, position and flux of individual arcs are strongly affected by the presence of substructures in the clusters. Removing substructures on spatial scales <~50kpc/h, roughly corresponding to mass scales <~5 10^{10}M_\odot/h, alters the image multiplicity of ~35% of the sources used in the simulations and causes position shifts larger than 5'' for ~40% of the arcs longer than 5''. We conclude that any model for cluster lens cannot neglect the effects of ellipticity, asymmetries and substructures. On the other hand, the high sensitivity of gravitational arcs to deviations from regular, smooth and symmetric mass distributions suggests that strong gravitational lensing is potentially a powerfull tool to measure the level of substructures and asymmetries in clusters.Comment: 16 pages, 18 figures. Accepted version. Version with full resolution images can be found at http://www.ita.uni-heidelberg.de/~massimo/sub/publications.htm

Transport properties and Langevin dynamics of heavy quarks and quarkonia in the Quark Gluon Plasma

Quark Gluon Plasma transport coefficients for heavy quarks and quark-antiquark pairs are computed through an extension of the results obtained for a hot QED plasma by describing the heavy-quark propagation in the eikonal approximation and by weighting the gauge field configurations with the Hard Thermal Loop effective action. It is shown that such a model allows to correctly reproduce, at leading logarithmic accuracy, the results obtained by other independent approaches. The results are then inserted into a relativistic Langevin equation allowing to follow the evolution of the heavy-quark momentum spectra. Our numerical findings are also compared with the ones obtained in a strongly-coupled scenario, namely with the transport coefficients predicted (though with some limitations and ambiguities) by the AdS/CFT correspondence.Comment: Minor changes. One figure added. Final version accepted for publication by Nucl. Phys.

Quantum fluctuations of vacuum stress tensors and spacetime curvatures

We analyze the quantum fluctuations of vacuum stress tensors and spacetime curvatures, using the framework of linear response theory which connects these fluctuations to dissipation mechanisms arising when stress tensors and spacetime metric are coupled. Vacuum fluctuations of spacetime curvatures are shown to be a sum of two contributions at lowest orders; the first one corresponds to vacuum gravitational waves and is restricted to light-like wavevectors and vanishing Einstein curvature, while the second one arises from gravity of vacuum stress tensors. From these fluctuations, we deduce noise spectra for geodesic deviations registered by probe fields which determine ultimate limits in length or time measurements. In particular, a relation between noise spectra characterizing spacetime fluctuations and the number of massless neutrino fields is obtained.Comment: 11 page

Superconducting Vortex‐Antivortex Pairs: Nucleation and Confinement in Magnetically Coupled Superconductor‐Ferromagnet Hybrids

Superconducting vortices are a well known class of vortices, each of them carrying a single magnetic flux quantum. In this chapter the authors present the results of low temperature Magnetic Force Microscopy experiments to investigate the nucleation and dynamics of superconducting vortices in magnetically coupled Superconductor/Ferromagnet (S/F) heterostructures made by Nb/Py. It is here shown that by controlling the thicknesses of both S and F layer, the formation of spontaneous vortex-antivortex pairs (V-AV) can be favored and their confinement and mobility can be tuned. The experimental results are compared with two theoretical models dealing with the spontaneous nucleation of V/AV pairs in the limits of S thickness respectively greater and smaller than the London penetration depth. It is shown that vortex nucleation and confinement is regulated by the intensity of the out-of-plane component of the magnetization with respect to a critical magnetization set by the thickness of both S and F layers. Additionally, external field cooling processes were used to probe in-field vortex nucleation and V-AV unbalancing, whereas the sweeping of an external magnetic field when below the superconducting critical temperature was used to force the vortex into motion, probing the vortex mobility/rigidity and the vortex avalanche events

Causes and outcomes of hyponatraemia at Mater Dei Hospital, Malta

CONTEXT: Hyponatraemia is the most common electrolyte balance disorder in clinical practice, amounting to 15–20% of casualty visits. While there is general agreement that associated mortality rates are high, most studies are uncontrolled.OBJECTIVE: To determine the characteristics, causes and outcome of severe hyponatraemia (<125 mmol/l) in hospitalised patients and to indentify mortality predictors.DESIGN: This is a retrospective case-controlled study of all medical admissions in the months of February, June and November, who at any point during the index admission developed a serum sodium <125 mmol/l. For each case, an age- and gender-matched control was identified.RESULTS: A total of 5195 medical admissions were reviewed. Of these, 193 patients had a sodium level <125 mmol/. 26 patients were excluded from the case group leaving a total of 167 cases and 193 controls. Length of hospital stay was more prolonged in the case group (12 vs 8 days, P<0.001). There was a highly significant excess mortality, both during the index admission (25% in cases vs 7% in controls (P < 0.001)) as well as till the end of the follow-up period (52% in cases vs 22% in controls (P<0.001)). Mortality was unrelated to severity of hyponatraemia. Patients who developed the lowest serum sodium later on during their admission (ie sodium levels continued falling during the admission or fell de novo), had a higher rate of mortality than patients whose lowest serum sodium was on the day of admission (64.3% vs 45%, P 0.019). A cox regression analysis showed that hyponatraemia (P<0.001), male gender (P 0.033), age (P 0.021), and serum creatinine level (P 0.008) were independent risk factors for mortality. There was no statistically significant difference between the rates of ITU admission at different levels of hyponatraemia <125 mmol/l (P=0.497). Thus, serum sodium levels of <125 mmol/l should be used to identify patients who need more intensive monitoring and therapy irrespective of the degree of hyponatraemia. Only 41% of cases developed neurological symptoms, of these, confusion and altered level of consciousness were the more prevalent at 12% each, followed by falls (9%), unsteady gait (4%) and seizures (4%). The cause for hyponatraemia was frequently poorly evaluated and in 23% of cases no definite diagnosis was made.CONCLUSION: Data on assessment, investigation and management of hyponatraemia illustrates variability and shortcomings in clinical practice. The question remains whether the relationship between hyponatraemia and increased mortality is causal or associative.peer-reviewe

Buprenorphine for neuropathic pain in adults

BACKGROUND Opioid drugs, including buprenorphine, are commonly used to treat neuropathic pain, and are considered effective by some professionals. Most reviews have examined all opioids together. This review sought evidence specifically for buprenorphine, at any dose, and by any route of administration. Other opioids are considered in separate reviews. OBJECTIVES To assess the analgesic efficacy of buprenorphine for chronic neuropathic pain in adults, and the adverse events associated with its use in clinical trials. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from inception to 11 June 2015, together with reference lists of retrieved papers and reviews, and two online study registries. SELECTION CRITERIA We included randomised, double-blind studies of two weeks' duration or longer, comparing any oral dose or formulation of buprenorphine with placebo or another active treatment in chronic neuropathic pain. DATA COLLECTION AND ANALYSIS Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality. We did not carry out any pooled analyses. MAIN RESULTS Searches identified 10 published studies, and one study with results in ClinicalTrials.gov. None of these 11 studies satisfied our inclusion criteria, and so we included no studies in the review. AUTHORS' CONCLUSIONS There was insufficient evidence to support or refute the suggestion that buprenorphine has any efficacy in any neuropathic pain condition