An algorithm to enumerate all possible protein conformations verifying a set of distance constraints

International audienceBackground: The determination of protein structures satisfying distance constraints is an important problem in structural biology. Whereas the most common method currently employed is simulated annealing, there have been other methods previously proposed in the literature. Most of them, however, are designed to find one solution only. Results: In order to explore exhaustively the feasible conformational space, we propose here an interval Branch-and-Prune algorithm (iBP) to solve the Distance Geometry Problem (DGP) associated to protein structure determination. This algorithm is based on a discretization of the problem obtained by recursively constructing a search space having the structure of a tree, and by verifying whether the generated atomic positions are feasible or not by making use of pruning devices. The pruning devices used here are directly related to features of protein conformations. Conclusions: We described the new algorithm iBP to generate protein conformations satisfying distance constraints, that would potentially allows a systematic exploration of the conformational space. The algorithm iBP has been applied on three α-helical peptides

Prevalence study of mental disorders in an Italian region. Preliminary report

Background Mental disorders are a major public health problem. However, over the last few years, there have been few studies aimed at evaluating their diffusion. Therefore, this study aimed at evaluating: the prevalence of the most frequent psychiatric disorders in the general population residing in Tuscany using a clinical scale administered by trainee in psychiatry. Methods The study was carried out on a representative sample of the general population aged > 18 years, randomly extracted from the register of patients in the Tuscany region, adopting a proportional sampling method stratified by gender, age group and Local Health Units (LHU). Each person was contacted by letter followed by a phone call from an operator who makes an appointment with the trainee in psychiatry. The diagnostic interview conducted was the Mini-International Neuropsychiatric Interview (MINI). Point and lifetime prevalence by gender and age group were calculated. Differences and associations were considered statistically significant if their p-values were less than 0.05. Results Of the 408 people involved, 390 people were enrolled (of which 52.6% female). The 28.5% of the sample had been affected by a psychiatric disorder during their lifetime. In their lifetime, the most represented psychiatric disorders were major depressive episode (20.4%), major depressive disorder (17.0%) and panic disorder (10.3%), more frequent in the female than the male group. Current conditions were predominantly major depressive episode (3.1%) and agoraphobia (2.8%). A 5.9% rate of current suicidal ideation was also found. Conclusions In the general population, 28.5% of people reported a psychiatric disorder during their lifetime. This prevalence is considerably higher than that reported in a previous study carried out in central Italy

The small GTPase Rab29 is a common regulator of immune synapse assembly and ciliogenesis

Acknowledgements We wish to thank Jorge Galán, Gregory Pazour, Derek Toomre, Giuliano Callaini, Joel Rosenbaum, Alessandra Boletta and Francesco Blasi for generously providing reagents and for productive discussions, and Sonia Grassini for technical assistance. The work was carried out with the financial support of Telethon (GGP11021) and AIRC.Peer reviewedPostprin

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field