The multiple autoimmune syndromes. A clue for the autoimmune tautology

The multiple autoimmune syndromes (MAS) consist on the presence of three or more well-defined autoimmune diseases (ADs) in a single patient. The aim of this study was to analyze the clinical and genetic characteristics of a large series of patients with MAS. A cluster analysis and familial aggregation analysis of ADs was performed in 84 patients. A genome-wide microsatellite screen was performed in MAS families, and associated loci were investigated through the pedigree disequilibrium test. Systemic lupus erythematosus (SLE), autoimmune thyroid disease (AITD), and Sjögren's syndrome together were the most frequent ADs encountered. Three main clusters were established. Aggregation for type 1 diabetes, AITD, SLE, and all ADs as a trait was found. Eight loci associated with MAS were observed harboring autoimmunity genes. The MAS represent the best example of polyautoimmunity as well as the effect of a single genotype on diverse phenotypes. Its study provides important clues to elucidate the common mechanisms of ADs (i.e., autoimmune tautology). © Springer Science+Business Media, LLC 2012.

Agregación de autoinmunidad en familias extremas con Síndrome de Sjogren: una aproximación a la medicina personalizada

Objetivo: investigar la agregación de autoinmunidad en familiares en primer grado (FPG) de probandos con Síndrome de Sjogren (SS) con poliautoinmunidad y autoinmunidad familiar. Metodología: estudio de corte transversal en el cual se incluyeron 14 familias de mujeres con SS. Se realizó un análisis genético a través del cálculo de riesgos relativos para cada enfermedad autoinmune (EAI). La agregación familiar se calculó para los FPG, teniendo en cuenta la prevalencia de la enfermedad en cada familia y en la población general. Resultados: Se analizaron un total de 112 individuos, con una media de edad de 51.7 años ± 12.9. Veintidós individuos de los FPG tuvieron al menos una EAI (28.2%). La prevalencia de poliautoinmunidad fue del 93% y 6.4% en probandos y FPG, respectivamente. Se observaron valores que soportaron la agregación familiar para varias EAIs, entre ellas púrpura trombocitopénica idiopática, granulomatosis con poliangeiitis, síndrome antifosfolipídico, lupus eritematoso sistémico y artritis reumatoide. Discusión: estos resultados indican que las EAIs se agregan entre familias con SS, sugiriendo un origen común entre ellas. La elección de fenotipos clínicamente relevantes representa una nueva aproximación a la medicina personalizada en autoinmunidad.

New insights on growth mechanisms of protein clusters at surfaces: an AFM and simulation study

Despite its relevance to a wide range of technological and fundamental areas, a quantitative understanding of protein surface clustering dynamics is often lacking. In inorganic crystal growth, surface clustering of adatoms is well described by diffusion-aggregation models. In such models, the statistical properties of the aggregate arrays often reveal the molecular scale aggregation processes. We investigate the potential of these theories to reveal hitherto hidden facets of protein clustering by carrying out concomitant observations of lysozyme adsorption onto mica surfaces, using atomic force microscopy. and Monte Carlo simulations of cluster nucleation and growth. We find that lysozyme clusters diffuse across the substrate at a rate that varies inversely with size. This result suggests which molecular scale mechanisms are responsible for the mobility of the proteins on the substrate. In addition the surface diffusion coefficient of the monomer can also be extracted from the comparison between experiments and simulations. While concentrating on a model system of lysozyme-on-mica, this 'proof of concept' study successfully demonstrates the potential of our approach to understand and influence more biomedically applicable protein-substrate couples.

Reversible state transition in nanoconfined aqueous solutions

Using molecular dynamics simulations, we find a reversible transition between the dispersion and aggregation states of solute molecules in aqueous solutions confined in nanoscale geometry, which is not observed in macroscopic systems. The nanoscale confinement also leads to a significant increase of the critical aggregation concentration (CAC). A theoretical model based on Gibbs free energy calculation is developed to describe the simulation results. It indicates that the reversible state transition is attributed to the low free energy barrier (of order kBT) in between two energy minima corresponding to the dispersion and aggregation states, and the enhancement of the CAC results from the fact that at lower concentrations the number of solute molecules is not large enough to allow the formation of a stable cluster in the confined systems.

Structure and magnetic properties of polydisperse ferrofluids: a molecular dynamics study

We study by Langevin molecular dynamics simulations systematically the influence of polydispersity in the particle size, and subsequently in the dipole moment, on the physical properties of ferrofluids. The polydispersity is in a first approximation modeled by a bidisperse system that consists of small and large particles at different ratios of their volume fractions. In the first part of our investigations the total volume fraction of the system is fixed, and the volume fraction phi(L) of the large particles is varied. The initial susceptibility chi and magnetization curve of the systems show a strong dependence on the value of phi(L). With the increase of phi(L), the magnetization M of the system has a much faster increment at weak fields, and thus leads to a larger chi. We performed a cluster analysis that indicates that this is due to the aggregation of the large particles in the systems. The average size of these clusters increases with increasing phi(L). In the second part of our investigations, we fixed the volume fraction of the large particles, and increased the volume fraction phi(S) of the small particles in order to study their influence on the chain formation of the large ones. We found that the average aggregate size formed by large particles decreases when phi(S) is increased, demonstrating a significant effect of the small particles on the structural properties of the system. A topological analysis of the structure reveals that the majority of the small particles remain nonaggregated. Only a small number of them are attracted to the ends of the chains formed by large particles.

Computer simulation study of equilibrium properties of magnetic dipolar fluids

Langevin dynamics simulations are used to investigate the equilibrium magnetization properties and structure of magnetic dipolar fluids. The influence of using different boundary conditions are systematically studied. Simulation results on the initial susceptibility and magnetization curves are compared with theoretical predictions. The effect of particle aggregation is discussed in detail by performing a cluster analysis of the microstructure.

Engineering the electronic bandgaps and band edge positions in carbon-substituted 2D boron nitride: a first-principles investigation

Modification of graphene to open a robust gap in its electronic spectrum is essential for its use in field effect transistors and photochemistry applications. Inspired by recent experimental success in the preparation of homogeneous alloys of graphene and boron nitride (BN), we consider here engineering the electronic structure and bandgap of C2xB1−xN1−x alloys via both compositional and configurational modification. We start from the BN end-member, which already has a large bandgap, and then show that (a) the bandgap can in principle be reduced to about 2 eV with moderate substitution of C (x < 0.25); and (b) the electronic structure of C2xB1−xN1−x can be further tuned not only with composition x, but also with the configuration adopted by C substituents in the BN matrix. Our analysis, based on accurate screened hybrid functional calculations, provides a clear understanding of the correlation found between the bandgap and the level of aggregation of C atoms: the bandgap decreases most when the C atoms are maximally isolated, and increases with aggregation of C atoms due to the formation of bonding and anti-bonding bands associated with hybridization of occupied and empty defect states. We determine the location of valence and conduction band edges relative to vacuum and discuss the implications on the potential use of 2D C2xB1−xN1−x alloys in photocatalytic applications. Finally, we assess the thermodynamic limitations on the formation of these alloys using a cluster expansion model derived from first-principles.