New variants of alpha-1-antitrypsin: structural simulations and clinical expression.

Background: Alpha-1 antitrypsin deficiency (AATD) is characterized by reduced serum levels of the AAT protein and predisposes to liver and lung disease. The characterization at structural level of novel pathogenic SERPINA1 mutants coding for circulating AAT could provide novel insights into the mechanisms of AAT misfolding. The present study aimed to provide a practical framework for the identification and analysis of new AAT mutations, combining structural simulations and clinical data.

Nonlinear complexification of periodic orbits in the generalized Landau scenario.

We have found a way for penetrating the space of the dynamical systems toward systems of arbitrary dimension exhibiting the nonlinear mixing of a large number of oscillation modes through which extraordinarily complex time evolutions may arise. The system design is based on assuring the occurrence of a number of Hopf bifurcations in a set of fixed points of a relatively generic system of ordinary differential equations, in which the main peculiarity is that the nonlinearities appear through functions of a linear combination of the system variables. The paper outlines the design procedure and presents a selection of numerical simulations with a variety of designed systems whose dynamical behaviors are really rich and full of unknown features.

Conservation and variability of hepatitis B core at different chronic hepatitis stages.

Background: Since it is currently not possible to eradicate hepatitis B virus (HBV) infection with existing treatments, research continues to uncover new therapeutic strategies. HBV core protein, encoded by the HBV core gene (), intervenes in both structural and functional processes, and is a key protein in the HBV life cycle. For this reason, both the protein and the gene could be valuable targets for new therapeutic and diagnostic strategies.

Unraveling the effect of silent, intronic and missense mutations on splicing: contribution of next generation sequencing in the study of mRNA.

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on mRNA. This study aimed to elucidate the true effects of 18 mutations on mRNA processing, investigate the contribution of next-generation sequencing to mRNA study in von Willebrand disease, and compare the findings with prediction.