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

Nonlinear static procedures for state-dependent seismic fragility analysis of reinforced concrete buildings

This paper introduces a simplified methodology to develop state-dependent fragility relationships, based on nonlinear static analyses combined with the Cloud Capacity Spectrum Method. Capacity reduction factors for structural members are applied to simulate the attainment of a specific damage state under a mainshock. A cloud-based procedure is adopted to compute fragility analyses. The procedure is illustrated for a case-study building designed for gravity loads only. Results highlight the importance of considering the effect of cumulative damage in the fragility analysis of buildings. The proposed methodology may be used for seismic-risk assessment studies accounting for ground-motion sequences

Energy-based procedures for seismic fragility analysis of mainshock-damaged buildings

In recent decades, significant research efforts have been devoted to developing fragility and vulnerability models for mainshock-damaged buildings, i.e., depending on the attained damage state after a mainshock ground motion (state-dependent fragility/vulnerability relationships). Displacement-based peak quantities, such as the maximum interstory drift ratio, are widely adopted in fragility analysis to define both engineering demands and structural capacities at the global and/or local levels. However, when considering ground-motion sequences, the use of peak quantities may lead to statistical inconsistencies (e.g., fragility curves’ crossings) due to inadequate consideration of damage accumulation. In this context, energy-based engineering demand parameters (EDPs), explicitly accounting for cumulative damage, can help address this issue. This paper provides an overview of recent findings on the development of aftershock-fragility models of mainshock-damaged buildings. Particular focus is given to state-of-the-art frameworks for fragility analyses based on cumulative damage parameters. Moreover, a literature review on damage indices and energy-based concepts and approaches in earthquake engineering is reported to better understand the main advantages of the mostly adopted energy-based parameters, as well as their limitations. Different refinement levels of seismic response analyses to derive fragility relationships of mainshock-damaged buildings are also discussed. Finally, the benefits of adopting energy-based EDPs rather than, or in addition to, peak quantities in state-dependent fragility analyses are demonstrated on a reinforced concrete frame building. Specifically, a refined lumped plasticity modeling approach is adopted, and sequential cloud-based time-history analyses of a Multi-Degree-of-Freedom (MDoF) model are carried out. The results highlight that energy-based approaches for fragility analysis effectively capture damage accumulation during earthquake sequences without inconsistencies in the obtained statistical models. On the other hand, estimating global or local structural capacity in terms of cumulative EDPs is still challenging. Further experimental data are needed to better calibrate the quantification of energy-based damaged states

Examination on total ozone column retrievals by Brewer spectrophotometry using different processing software

The availability of long-term records of the total ozone content (TOC) represents a valuable source of information for studies on the assessment of short-and long-term atmospheric changes and their impact on the terrestrial ecosystem. In particular, ground-based observations represent a valuable tool for validating satellite-derived products. To our knowledge, details about software packages for processing Brewer spectrophotometer measurements and for retrieving the TOC are seldom specified in studies using such datasets. The sources of the differences among retrieved TOCs from the Brewer instruments located at the Italian stations of Rome and Aosta, using three freely available codes (Brewer Processing Software, BPS; O3Brewer software; and European Brewer Network (EUBREWNET) level 1.5 products) are investigated here. Ground-based TOCs are also compared with Ozone Monitoring Instrument (OMI) TOC retrievals used as an independent dataset since no other instruments near the Brewer sites are available. The overall agreement of the BPS and O3Brewer TOC data with EUBREWNET data is within the estimated total uncertainty in the retrieval of total ozone from a Brewer spectrophotometer (1%). However, differences can be found depending on the software in use. Such differences become larger when the instrumental sensitivity exhibits a fast and dramatic drift which can affect the ozone retrievals significantly. Moreover, if daily mean values are directly generated by the software, differences can be observed due to the configuration set by the users to process single ozone measurement and the rejection rules applied to data to calculate the daily value. This work aims to provide useful information both for scientists engaged in ozone measurements with Brewer spectrophotometers and for stakeholders of the Brewer data products available on Web-based platforms

A sensitivity study on the mechanical properties of interface elements adopted in finite element analyses to simulate the interaction between soil and laterally loaded piles

An increasing number of offshore energy structures have been built recently on driven piles, ranging from jack- et piles with typical length-to-diameter (L/D) ratios of 10-40 to monopiles with far lower L/D ratios. The load-displacement behaviour of these foundations can be investigated by means of Finite Element (FE) analyses, for instance following the design methodology developed by the PISA Joint Industry Project (JIP). A challenging aspect of the modelling, for piles loaded either axially or laterally, is the simulation of the behaviour at the soil-pile interface with the adoption of suitable formulations for the interface elements and with representative mechanical properties. This paper presents a sensitivity study conducted on both the elastic and plastic properties of interface elements adopted in FE analyses of laterally loaded piles driven in chalk. The study benefited from the extensive field and laboratory test results collected during the ALPACA JIP and the corresponding pile tests. The aim of the paper is to provide guidance for numerical modelling on the selection of the most appropriate mechanical properties of interface elements to be used in the analyses of soil-pile interaction under lateral loading

Use of DPP4 inhibitors in Italy does not correlate with diabetes prevalence among COVID-19 deaths

In a nationwide study of 3,818 charts from patients with fatal COVID-19, we found that geographical differences in Dipeptidyl peptidase 4 (DPP4) inhibitors use did not correlate with diabetes prevalence among COVID-19 deaths, thus not supporting the hypothesis of a clinically relevant involvement of DPP4 in COVID-19 development and progression

Nursing student attitudes towards older people: validity and reliability of the Italian version of the Kogan Attitudes towards Older People scale

Aim. This paper reports a study testing the validity and reliability of the Italian version of the Kogan Attitude towards Older People scale. Background. Nursing students’ attitudes towards older people can affect their preference for working with them. One of the most common instruments used to assess these attitudes is the Kogan Attitude towards Older People scale. Previous validation studies performed on college students internationally have demonstrated good reliability and validity. The psychometric properties of the Italian version have not yet been tested. Design. A cross-sectional, descriptive study. Method. The study was conducted from March–June 2010 with a convenience sample of nursing students attending two Italian universities. Reliability was evaluated using internal consistency and item-to-total correlation. Content and construct validity were evaluated using a content validity index and principal factor analysis. Results. A total of 1637 nursing students participated in the study. Two factors were extracted from the factor analysis: prejudice describing a negative disposition and appreciation indicating a favourable feeling and opinion towards older people. Conclusion. The Kogan Attitude towards Older People scale applied to Italian nursing students exhibited good internal consistency. The two-dimensional construct of the scale was congruent with some, but not all, results of previous studies due to methodological differences among the studies. Based on the study findings, the scale can be recommended for future research studies in Italy including use as pre/post-test measurement associated with nursing education programmes

Antimicrobial peptides from plants: stabilization of the core of a tomato defensin by intramolecular disulfide bond

Cysteine-containing antimicrobial peptides of diverse phylogeny share a common structural signature, the γ core, characterized by a strong polarization of charges in two antiparallel β sheets. In this work, we analyzed peptides derived from the tomato defensin SolyC07g007760 corresponding to the protein γ core and demonstrated that cyclization of the peptides, which results in segregation of positive charges to the turn region, produces peptides very active against Gram negative bacteria, such as Salmonella enterica and Helicobacter pylori. Interestingly, these peptides show very low hemolytic activity and thus represent a scaffold for the design of new antimicrobial peptides

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.