Claudio Donati

Dynamical Heterogeneities in a Supercooled Lennard-Jones Liquid

We present the results of a molecular dynamics computer simulation study in which we investigate whether a supercooled Lennard-Jones liquid exhibits dynamical heterogeneities. We evaluate the non-Gaussian parameter for the self part of the van Hove correlation function and use it to identify {open_quotes}mobile{close_quotes} particles. We find that these particles form clusters whose sizes grow with decreasing temperature. We also find that the relaxation time of the mobile particles is significantly shorter than that of the average particle, and that this difference increases with decreasing temperature. {copyright} {ital 1997} {ital The American Physical Society}

Microbiology in the post-genomic era

Genomics has revolutionized every aspect of microbiology. Now, 13 years after the first bacterial genome was sequenced, it is important to pause and consider what has changed in microbiology research as a consequence of genomics. In this article, we review the evolving field of bacterial typing and the genomic technologies that enable comparative analysis of multiple genomes and the metagenomes of complex microbial environments, and address the implications of the genomic era for the future of microbiology.

Structure and dynamics of the pan-genome of Streptococcus pneumoniae and closely related species

BackgroundStreptococcus pneumoniae is one of the most important causes of microbial diseases in humans. The genomes of 44 diverse strains of S. pneumoniae were analyzed and compared with strains of non-pathogenic streptococci of the Mitis group.ResultsDespite evidence of extensive recombination, the S. pneumoniae phylogenetic tree revealed six major lineages. With the exception of serotype 1, the tree correlated poorly with capsular serotype, geographical site of isolation and disease outcome. The distribution of dispensable genes - genes present in more than one strain but not in all strains - was consistent with phylogeny, although horizontal gene transfer events attenuated this correlation in the case of ancient lineages. Homologous recombination, involving short stretches of DNA, was the dominant evolutionary process of the core genome of S. pneumoniae. Genetic exchange occurred both within and across the borders of the species, and S. mitis was the main reservoir of genetic diversity of S. pneumoniae. The pan-genome size of S. pneumoniae increased logarithmically with the number of strains and linearly with the number of polymorphic sites of the sampled genomes, suggesting that acquired genes accumulate proportionately to the age of clones. Most genes associated with pathogenicity were shared by all S. pneumoniae strains, but were also present in S. mitis, S. oralis and S. infantis, indicating that these genes are not sufficient to determine virulence.ConclusionsGenetic exchange with related species sharing the same ecological niche is the main mechanism of evolution of S. pneumoniae. The open pan-genome guarantees the species a quick and economical response to diverse environments.

Growing range of correlated motion in a polymer melt on cooling towards the glass transition

Many liquids cooled to low temperatures form glasses (amorphous solids) instead of crystals. As the glass transition is approached, molecules become localized and relaxation times increase by many orders of magnitude. Many features of this ‘slowing down’ are reasonably well described by the mode-coupling theory of supercooled liquids. The ideal form of this theory predicts a dynamical critical temperature T c at which the molecules become permanently trapped in the ‘cage’ formed by their neighbours, and vitrification occurs. Although there is no sharp transition, because molecules do eventually escape their cage, its signature can still be observed in real and simulated liquids. Unlike conventional critical phenomena (such as the behaviour at the liquid–gas critical point), the mode-coupling transition is not accompanied by a diverging static correlation length. But simulation and experiment, show that liquids are dynamically heterogeneous, suggesting the possibility of a relevant ‘dynamical’ length scale characterizing the glass transition. Here we use computer simulations to investigate a melt of short, unentangled polymer chains over a range of temperatures for which the mode-coupling theory remains valid. We find that although density fluctuations remain short-ranged, spatial correlations between monomer displacements become long-ranged as T c is approached on cooling. In this way, we identify a growing dynamical correlation length, and a corresponding order parameter, associated with the glass transition. This finding suggests a possible connection between well established concepts in critical phenomena and the dynamics of glass-forming liquids.

A Second Pilus Type in Streptococcus pneumoniae Is Prevalent in Emerging Serotypes and Mediates Adhesion to Host Cells

Analysis of publicly available genomes of Streptococcus pneumoniae has led to the identification of a new genomic element containing genes typical of gram-positive pilus islets (PIs). Here, we demonstrate that this genomic region, herein referred to as PI-2 (consisting of pitA, sipA, pitB, srtG1, and srtG2) codes for a second functional pilus in pneumococcus. Polymerization of the PI-2 pilus requires the backbone protein PitB as well as the sortase SrtG1 and the signal peptidase-like protein SipA. Presence of PI-2 correlates with the genotype as defined by multilocus sequence typing and clonal complex (CC). The PI-2-positive CCs are associated with serotypes 1, 2, 7F, 19A, and 19F, considered to be emerging serotypes in both industrialized and developing countries. Interestingly, strains belonging to CC271 (where sequence type 271 is the predicted founder of the CC) contain both PI-1 and PI-2, as revealed by genome analyses. In these strains both pili are surface exposed and independently assembled. Furthermore, in vitro experiments provide evidence that the pilus encoded by PI-2 of S. pneumoniae is involved in adherence. Thus, pneumococci encode at least two types of pili that play a role in the initial host cell contact to the respiratory tract and are potential antigens for inclusion in a new generation of pneumococcal vaccines.

Streptococcus pneumoniae Contains 3 rlrA Pilus Variants That Are Clonally Related

BACKGROUND Pilus components of Streptococcus pneumoniae encoded by rlrA were recently shown to elicit protection in an animal model of infection. Limited data are available on the prevalence of the rlrA operon in pneumococci; therefore, we investigated its distribution and its antigenic variation among disease-causing strains. METHODS The prevalence of rlrA and its association with serotype and genotype were evaluated in a global panel of 424 pneumococci isolates (including the 26 drug-resistant clones described by the Pneumococcal Molecular Epidemiology Network). RESULTS The rlrA islet was found in 130 isolates (30.6%) of the defined collection. Sequence alignment of 15 rlrA islets defined the presence of 3 clade types, with an overall homology of 88%-92%. The presence or absence of a pilus-encoding operon correlated with S. pneumoniae genotype (P < .001), as determined by multilocus sequence typing, and not with serotype. Further investigation identified a positive trend of rlrA occurrence among antimicrobial-resistant pneumococci. CONCLUSIONS On the basis of S. pneumoniae genotype, it is possible to predict the incidence of the rlrA pilus operon in a collection of pneumococcal isolates. This will facilitate the development of a protein vaccine.

Growing Spatial Correlations of Particle Displacements in a Simulated Liquid on Cooling Toward the Glass Transition

We define a correlation function that quantifies the spatial correlation of single-particle displacements in liquids and amorphous materials. We show that for an equilibrium liquid this function is related to fluctuations in a bulk dynamical variable. We evaluate this function using computer simulations of an equilibrium glass-forming liquid, and show that long range spatial correlations of displacements emerge and grow on cooling toward the mode coupling critical temperature. [S0031-9007(99)09452-1] Liquids cooled toward their glass transition exhibit remarkable dynamical behavior [1]. The initial slowing of transport processes for liquids at temperatures T well above their glass transition temperature Tg is described by the mode coupling theory (MCT) [2], which predicts diverging relaxation times at a dynamical critical temperature Tc (in real and simulated liquids, this divergence is only apparent). The dynamical singularity of MCT occurs without a corresponding growing static correlation length associated with density or composition fluctuations [3]. Yet recent studies show that in the range of T described by MCT, simulated glass-forming liquids exhibit spatially heterogeneous dynamics [4 ‐6]. In this Letter, we define a correlation function that quantifies the spatial correlation of particle displacements and evaluate this function for a Lennard-Jones liquid. We find that spatial correlations of displacement arise and become long ranged on cooling toward Tc. First, we briefly review the conventional static correla

THEORY OF NON-LINEAR SUSCEPTIBILITY AND CORRELATION LENGTH IN GLASSES AND LIQUIDS

Abstract Within the framework of the effective potential theory of the structural glass transition, we calculate for the p-spin model and for a hard sphere liquid in the hypernetted chain approximation a static non-linear susceptibility related to a four-point density correlation function, and show that it diverges in mean field with exponent γ=1/2 as the critical temperature Tc is approached from below. When Tc is approached from above, we calculate for the p-spin model a time dependent non-linear susceptibility and show that there is a characteristic time where this susceptibility has a maximum, and that this time grows with decreasing T. This susceptibility diverges as Tc is approached from above, and has key features in common with a generalized susceptibility related to particle displacements, previously introduced to measure correlated particle motion in simulations of glass-forming liquids.

New evidences on the altered gut microbiota in autism spectrum disorders

BackgroundAutism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by social and behavioural impairments. In addition to neurological symptoms, ASD subjects frequently suffer from gastrointestinal abnormalities, thus implying a role of the gut microbiota in ASD gastrointestinal pathophysiology.ResultsHere, we characterized the bacterial and fungal gut microbiota in a cohort of autistic individuals demonstrating the presence of an altered microbial community structure. A fraction of 90% of the autistic subjects were classified as severe ASDs. We found a significant increase in the Firmicutes/Bacteroidetes ratio in autistic subjects due to a reduction of the Bacteroidetes relative abundance. At the genus level, we observed a decrease in the relative abundance of Alistipes, Bilophila, Dialister, Parabacteroides, and Veillonella in the ASD cohort, while Collinsella, Corynebacterium, Dorea, and Lactobacillus were significantly increased. Constipation has been then associated with different bacterial patterns in autistic and neurotypical subjects, with constipated autistic individuals characterized by high levels of bacterial taxa belonging to Escherichia/Shigella and Clostridium cluster XVIII. We also observed that the relative abundance of the fungal genus Candida was more than double in the autistic than neurotypical subjects, yet due to a larger dispersion of values, this difference was only partially significant.ConclusionsThe finding that, besides the bacterial gut microbiota, also the gut mycobiota contributes to the alteration of the intestinal microbial community structure in ASDs opens the possibility for new potential intervention strategies aimed at the relief of gastrointestinal symptoms in ASDs.

Reverse vaccinology in the 21st century: improvements over the original design

Reverse vaccinology (RV), the first application of genomic technologies in vaccine research, represented a major revolution in the process of discovering novel vaccines. By determining their entire antigenic repertoire, researchers could identify protective targets and design efficacious vaccines for pathogens where conventional approaches had failed. Bexsero, the first vaccine developed using RV, has recently received positive opinion from the European Medicines Agency. The use of RV initiated a cascade of changes that affected the entire vaccine development process, shifting the focus from the identification of a list of vaccine candidates to the definition of a set of high throughput screens to reduce the need for costly and labor intensive tests in animal models. It is now clear that a deep understanding of the epidemiology of vaccine candidates, and their regulation and role in host‐pathogen interactions, must become an integral component of the screening workflow. Far from being outdated by technological advancements, RV still represents a paradigm of how high‐throughput technologies and scientific insight can be integrated into biotechnology research.