The antioxidant properties of Ce-containing bioactive glass nanoparticles explained by Molecular Dynamics simulations

Molecular dynamics simulations of two glass nanoparticles with composition 25Na2O·25CaO 50SiO2 mol% (Ce-K NP) and 46.1SiO2·24.4Na2O·26.9CaO· 2.6P2O5 mol.% (Ce-BG NP) doped with 3.6 mol% of CeO2 have been carried out in order to explain the enhanced antioxidant properties of the former glass with respect to the latter. The present models show that the different catalase mimetic activity of the two NPs is related to the Ce3+/Ce4+ ratio exposed at their surface. In fact, this ratio is about 3.5 and 13 in the bulk and at the surface of the Ce-BG NP, and 1.0 and 2.1 in the bulk and at the surface of the Ce-K NPs, respectively. Since both oxidation states are necessary for the catalysis of the dismutation reaction of hydrogen peroxides, NPs with a very high Ce3+/Ce4+ ratio possess poorer antioxidant properties. Moreover, our simulations reveal that the already low silicate connectivity found in the bulk glasses examined here is further reduced on the nanoparticle surface, whereas the Na+/Ca2+ ratio rapidly increases. Sodium, calcium and cerium sites in proximity of the surface are found to be under-coordinated, prone to quickly react with water present in physiological environments, thus accelerating the glass biodegradatio

Folding mechanisms steer the amyloid fibril formation propensity of highly homologous proteins

Significant advances in the understanding of the molecular determinants of fibrillogenesis can be expected from comparative studies of the aggregation propensities of proteins with highly homologous structures but different folding pathways. Here, we fully characterize, by means of stopped-flow, T-jump, CD and DSC experiments, the unfolding mechanisms of three highly homologous proteins, zinc binding Ros87 and Ml153-149 and zinc-lacking Ml452-151. The results indicate that the three proteins significantly differ in terms of stability and (un)folding mechanisms. Particularly, Ros87 and Ml153-149 appear to be much more stable to guanidine denaturation and are characterized by folding mechanisms including the presence of an intermediate. On the other hand, metal lacking Ml452-151 folds according to a classic two-state model. Successively, we have monitored the capabilities of Ros87, Ml452-151 and Ml153-149 to form amyloid fibrils under native conditions. Particularly, we show, by CD, fluorescence, DLS, TEM and SEM experiments, that after 168 hours, amyloid formation of Ros87 has started, while Ml153-149 has formed only amorphous aggregates and Ml452-151 is still monomeric in solution. This study shows how metal binding can influence protein folding pathways and thereby control conformational accessibility to aggregation-prone states, which in turn changes aggregation kinetics, shedding light on the role of metal ions in the development of protein deposition diseases

Naposomes: a new class of peptide-derivatized, target-selectivemultimodal nanoparticles for imaging and therapeutic applications

Modified supramolecular aggregates for selective delivery of contrast agents and/or drugs are examined with a focus on a new class of peptide-derivatized nanoparticles: naposomes. These nanoparticles are based on the co‑aggregation of two different amphiphilic monomers that give aggregates of different shapes and sizes (micelles, vesicles and liposomes) with diameters ranging between 10 and 300 nm. Structural properties and in vitro and in vivo behaviors are discussed. For the high relaxitivity values (12–19 mM-1s-1) and to detect for the presence of a surface exposed peptide, the new peptide-derived supramolecular aggregates are very promising candidates as targetselective MRI contrast agents. The efficiency of surface-exposed peptides in homing these nanovectors to a specific target introduces promising new opportunities for the development of diagnostic and therapeutic agents with high specificity toward the biological target and reduced toxic side effects on nontarget organs

Supramolecular aggregates containing lipophilic Gd(III) complexes as contrast agents in MRI

Magnetic resonance imaging (MRI) contrast agents based on paramagnetic gadolinium complexes are widely used in biomedical research and diagnosis. Their application is intended to improve efficacy of MRI providing physiological information along with the impressive anatomical detail already obtained by images without contrast. The classical gadolinium complexes currently used for MRI contrast enhancement are all lowmolecularweightcompounds that rapidly equilibrate between the intra and extravascular spaces after intravenous administration. In order to obtain gadolinium-based agents with different pharmacokinetic properties, supramolecular aggregates such as micelles and liposomes have been recently proposed. Micelles and liposomes, obtained by the aggregation of lipophilic gadolinium complexes are here described, with the aim to correlate their structural and relaxometric properties.We report on the state of the art in the development of supramolecular aggregates obtained by self-assembly of lipophilic gadolinium complexes and aggregates in which lipophilic gadolinium complexes are assembled with surfactants. Moreover aggregates derivatized with bioactive molecules, such as peptides and antibodies, acting as target selective MRI contrast agents are described

Computational Modeling of Silicate Glasses: A Quantitative Structure-Property Relationship Perspective

This article reviews the present state of Quantitative Structure-Property Relationships (QSPR) in glass design and gives an outlook into future developments. First an overview is given of the statistical methodology, with particular emphasis to the integration of QSPR with molecular dynamics simulations to derive informative structural descriptors. Then, the potentiality of this approach as a tool for interpretative and predictive purposes is highlighted by a number of recent inspiring applications

Calibrating whole building energy model: a case study using BEMS data

This paper describes a Calibration methodology which is specifically configured to best match actual building performance, based on a case study conducted to calibrate whole building energy model using Building Energy Management System (BEMS) measured data. It details the calibration approach which was designed to meet the specific characteristic of the spaces, systems and energy use in the pilot school building. Two calibration methods were developed; one is for electrical and the other is for thermal energy along with calibrated weather file. The result shows excellent correlation with the measured electricity and room air temperature and demonstrates the effectiveness of the methodology. Mean Bias Error (MBE) and Cumulative Variation of Root Mean Squared Error (CVRMSE) for electricity consumption is 6% and 14% respectively and -5 and 7% for air temperature

Leachate Analyses of volcanic ashes from the 2010 Eyjafjallaj\uf6kull eruption

Volcanic processes which lead to eruptions can be investigated by monitoring a variety of parameters, including the composition of ash leachates. Fine-grained tephra erupted from active vents, and transported through volcanic plumes, can adsorb, and therefore rapidly scavenge, volatile elements such as sulphur, halogens, and metal species in the form of soluble salts adhering to ash surfaces. Analysis of such water-soluble surface materials is a suitable complement for the remote sensing of volcanic gases at inaccessible volcanoes. The April 2010 Eyjafjallaj\uf6kull eruption has been characterised by several distinct phases, with an initial effusion of alkali basalt on the volcano's northeast flank since March 20th, followed (since April 14th) by a complex summit, sustained, explosive to mixed activity, characterised by trachyandesitic magma The first phase of the summit eruption (14 to 18 April) was initially characterised by interaction between glacial meltwater from the icecap and erupting magma, and by three main pulses during which dark ash plumes were dispersed to the SE and S. Following a decrease in the intensity in explosive activity associated to the emission of a lava flow (from 19 April to 4 May), activity renewed in intensity on 5 May, when an ash-laden plume, up to 10 km in height, was continuously dispersed until May 18. Activity progressively declined and eruption closed on 9 June [1]. Here, we report on the chemical composition of leachates from volcanic ash samples deposited during the Eyjafjallaj\uf6kull explosive phase (from 14 April to 8 May). Twenty-eight freshly fallen volcanic ash samples were collected at various distances from the eruptive vent, and their leached solutions were analyzed for major and trace elements. We show that ash leachate solutions from Eyjafjallaj\uf6kull are dominated - among cations - by Na and Ca, while they display nearly equal S:Cl:F abundances (mean S/Cl and S/F molar ratios of 1.04 and 0.76 respectively), as characteristic of divergent-plate and within-plate volcanism. The good correlations between Ca and F (r2=0.8), Ca and SO4 (r2=0.7), and Na and Cl (r2=0.9) in ash leachates suggest that fluorite, anhydrite, and halite were the most likely soluble surface minerals formed in the plume (and therefore leached during our experiments). These correlations in the extracted solutions also indicate that either the sources of cations and anions in ash leachates were the same (e.g. direct condensation of NaCl(g) and CaSO4(g) from the plume) or, more probably, that the highest the condensation of plume acidic compounds (e.g., SO2(g), HCl(g), HF(g)) on ash, the largest the leaching of cations from silicate fragments. Indeed, our data bring evidence for that the extent of gas-ash reaction (likely, a proxy for ash residence time in the plume) was a key casual factor in determining ash leachate composition. Samples from the 4- 8th May eruptive period, showing the most acid pH values (4.5-5.5), consistently have the highest abundances for all elements, and especially Mg, S and F. Large variations in S and halogens proportions are observed in our dataset, with samples from the 4-8th May eruptive period showing the highest S/Cl and lowest Cl/F ratios. To interpret these variations, and particularly to verify whether they reflect changes in plume gas composition, in gas-ash reaction dynamics and rates,2]will require in-depth comparison with direct (FTIR) measurement of the Eyjafjallaj\uf6kull gas plume[2] . [1] Hoskuldsson, A., et al., 2011. Geophysical Research Abstracts Vol. 13, EGU2011-14165, 2011; [2] Allard, P., et al., 2010. Abstract V53F-07 presented at Fall Meeting, AGU, San Francisco, Calif. 13-17 Dec.

Tunable diode laser measurements of hydrothermal/volcanic CO2 and implications for the global CO2 budget

Quantifying the CO2 flux sustained by low-temperature fumarolic fields in hydrothermal/volcanic environments has remained a challenge, to date. Here, we explored the potential of a commercial infrared tunable laser unit for quantifying such fumarolic volcanic/hydrothermal CO2 fluxes. Our field tests were conducted between April 2013 and March 2014 at Nea Kameni (Santorini, Greece), Hekla and Krýsuvík (Iceland) and Vulcano (Aeolian Islands, Italy). At these sites, the tunable laser was used to measure the path-integrated CO2 mixing ratios along cross sections of the fumaroles' atmospheric plumes. By using a tomographic post-processing routine, we then obtained, for each manifestation, the contour maps of CO2 mixing ratios in the plumes and, from their integration, the CO2 fluxes. The calculated CO2 fluxes range from low (5.7 ± 0.9 t d−1; Krýsuvík) to moderate (524 ± 108 t d−1; La Fossa crater, Vulcano). Overall, we suggest that the cumulative CO2 contribution from weakly degassing volcanoes in the hydrothermal stage of activity may be significant at the global scale