Metabolic and vascular effect of the mediterranean diet

Several studies indicated how dietary patterns that were obtained from nutritional cluster analysis can predict disease risk or mortality. Low-grade chronic inflammation represents a background pathogenetic mechanism linking metabolic risk factors to increased risk of chronic degenerative diseases. A Mediterranean diet (MeDi) style has been reported as associated with a lower degree of inflammation biomarkers and with a protective role on cardiovascular and cerebrovascular events. There is heterogeneity in defining the MedDiet, and it can, owing to its complexity, be considered as an exposome with thousands of nutrients and phytochemicals. Recently, it has been reported a novel positive association between baseline plasma ceramide concentrations and cardiovascular events and how adherence to a Mediterranean Diet-style may influence the potential negative relationship between elevated plasma ceramide concentrations and cardiovascular diseases (CVD). Several randomized controlled trials (RCTs) showed the positive effects of the MeDi diet style on several cardiovascular risk factors, such as body mass index, waist circumference, blood lipids, blood pressure, inflammatory markers and adhesion molecules, and diabetes and how these advantages of the MeDi are maintained in comparison of a low-fat diet. Some studies reported a positive effect of adherence to a Mediterranean Diet and heart failure incidence, whereas some recent studies, such as the PREDIMED study, showed that the incidence of major cardiovascular events was lower among those assigned to MeDi supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet. New studies are needed to better understand the molecular mechanisms, whereby the MedDiet may exercise its effects. Here, we present recent advances in understanding the molecular basis of MedDiet effects, mainly focusing on cardiovascular diseases, but also discussing other related diseases. We review MedDiet composition and assessment as well as the latest advances in the genomic, epigenomic (DNA methylation, histone modifications, microRNAs, and other emerging regulators), transcriptomic (selected genes and whole transcriptome), and metabolomic and metagenomic aspects of the MedDiet effects (as a whole and for its most typical food components). We also present a review of the clinical effects of this dietary style underlying the biochemical and molecular effects of the Mediterranean diet. Our purpose is to review the main features of the Mediterranean diet in particular its benefits on human health, underling the anti-inflammatory, anti-oxidant and anti-atherosclerotic effects to which new knowledge about epigenetic and gut-microbiota relationship is recently added

Enhancing Fault / Intrusion Tolerance through Design and Configuration Diversity

Fault/intrusion tolerance is usually the only viable way of improving the system dependability and security in the presence of continuously evolving threats. Many of the solutions in the literature concern a specific snapshot in the production or deployment of a fault-tolerant system and no immediate considerations are made about how the system should evolve to deal with novel threats. In this paper we outline and evaluate a set of operating systems’ and applications’ reconfiguration rules which can be used to modify the state of a system replica prior to deployment or in between recoveries, and hence increase the replicas chance of a longer intrusion-free operation

FOREVER: Fault/intrusiOn REmoVal through Evolution & Recovery

The goal of the FOREVER project is to develop a service for Fault/intrusiOn REmoVal through Evolution & Recovery. In order to achieve this goal, our work addresses three main tasks: the definition of the FOREVER service architecture; the analysis of how diversity techniques can improve resilience; and the evaluation of the FOREVER service. The FOREVER service is an important contribution to intrustion-tolerant replication middleware and significantly enhances the resilience

Dynamical fingerprints for probing individual relaxation processes in biomolecular dynamics with simulations and kinetic experiments

There is a gap between kinetic experiment and simulation in their views of the dynamics of complex biomolecular systems. Whereas experiments typically reveal only a few readily discernible exponential relaxations, simulations often indicate complex multistate behavior. Here, a theoretical framework is presented that reconciles these two approaches. The central concept is “dynamical fingerprints” which contain peaks at the time scales of the dynamical processes involved with amplitudes determined by the experimental observable. Fingerprints can be generated from both experimental and simulation data, and their comparison by matching peaks permits assignment of structural changes present in the simulation to experimentally observed relaxation processes. The approach is applied here to a test case interpreting single molecule fluorescence correlation spectroscopy experiments on a set of fluorescent peptides with molecular dynamics simulations. The peptides exhibit complex kinetics shown to be consistent with the apparent simplicity of the experimental data. Moreover, the fingerprint approach can be used to design new experiments with site-specific labels that optimally probe specific dynamical processes in the molecule under investigation

Prosocial and aggressive behavior occurrence in young athletes: Field research results in six European countries

Aggression and violence among youth areresearched as social phenomena in sport. This paper was designed to determine the occurrence of these behaviors as well as prosocial behaviorsamong young athletes. The current paper is a research report aiming to detect the frequency of aggressive behavior, social exclusion, prosocial behavior and cohesion in the youth environment, the frequency of personal experience of peer violence or social exclusion, and to evaluate cross-national differences in terms of occurrence of these phenomena. The field research was conducted in six European countries (Austria, Bosnia and Herzegovina, Croatia, Italy, Lithuania, and Serbia) on a sample of 482 children aged 6 to 16. The conducted questionnaire consisted of pre-existing scales and measures for specific behaviors and social aspects that formed the Youth Environment Assessment and Youth Characteristics Questionnaire. Previous personal experience of violence and social exclusion determined groups in the sample. One-way ANOVA and discriminant analysis were conducted to compare various variables and groups within the sample. The results have shown that aggressive and social exclusion behaviors are rare or very rare, predominantly in the form of verbal aggression in the sports club environment. The results of the conducted discriminant analysis indicate that prosocial and cohesion behaviors occur "quite often" to "often" among sports club athletes' samples. The percentage of athletes who have had personal experience of violence or social exclusion in the last two years and whose feeling of hurt by that experience was assessed as "a lot" or "fully" on the measurement scale is estimated to be approximately 25%. Mild cross-national differences emerged in the overmentioned variables, probably due to the sample specificity, or to cultural variety. The results indicate the need for longitudinal research on this topic since the sport is an environment in which cohesion can be developed among young athletes, but it is not free from social exclusion or aggression

β-hairpin-mediated formation of structurally distinct multimers of neurotoxic prion peptides

Protein misfolding disorders are associated with conformational changes in specific proteins, leading to the formation of potentially neurotoxic amyloid fibrils. During pathogenesis of prion disease, the prion protein misfolds into β-sheet rich, protease-resistant isoforms. A key, hydrophobic domain within the prion protein, comprising residues 109–122, recapitulates many properties of the full protein, such as helix-to-sheet structural transition, formation of fibrils and cytotoxicity of the misfolded isoform. Using all-atom, molecular simulations, it is demonstrated that the monomeric 109–122 peptide has a preference for α-helical conformations, but that this peptide can also form β-hairpin structures resulting from turns around specific glycine residues of the peptide. Altering a single amino acid within the 109–122 peptide (A117V, associated with familial prion disease) increases the prevalence of β-hairpin formation and these observations are replicated in a longer peptide, comprising residues 106–126. Multi-molecule simulations of aggregation yield different assemblies of peptide molecules composed of conformationally-distinct monomer units. Small molecular assemblies, consistent with oligomers, comprise peptide monomers in a β-hairpin-like conformation and in many simulations appear to exist only transiently. Conversely, larger assemblies are comprised of extended peptides in predominately antiparallel β-sheets and are stable relative to the length of the simulations. These larger assemblies are consistent with amyloid fibrils, show cross-β structure and can form through elongation of monomer units within pre-existing oligomers. In some simulations, assemblies containing both β-hairpin and linear peptides are evident. Thus, in this work oligomers are on pathway to fibril formation and a preference for β-hairpin structure should enhance oligomer formation whilst inhibiting maturation into fibrils. These simulations provide an important new atomic-level model for the formation of oligomers and fibrils of the prion protein and suggest that stabilization of β-hairpin structure may enhance cellular toxicity by altering the balance between oligomeric and fibrillar protein assemblies

Hydrogen-Bond Driven Loop-Closure Kinetics in Unfolded Polypeptide Chains

Characterization of the length dependence of end-to-end loop-closure kinetics in unfolded polypeptide chains provides an understanding of early steps in protein folding. Here, loop-closure in poly-glycine-serine peptides is investigated by combining single-molecule fluorescence spectroscopy with molecular dynamics simulation. For chains containing more than 10 peptide bonds loop-closing rate constants on the 20–100 nanosecond time range exhibit a power-law length dependence. However, this scaling breaks down for shorter peptides, which exhibit slower kinetics arising from a perturbation induced by the dye reporter system used in the experimental setup. The loop-closure kinetics in the longer peptides is found to be determined by the formation of intra-peptide hydrogen bonds and transient β-sheet structure, that accelerate the search for contacts among residues distant in sequence relative to the case of a polypeptide chain in which hydrogen bonds cannot form. Hydrogen-bond-driven polypeptide-chain collapse in unfolded peptides under physiological conditions found here is not only consistent with hierarchical models of protein folding, that highlights the importance of secondary structure formation early in the folding process, but is also shown to speed up the search for productive folding events