CLP-based protein fragment assembly

The paper investigates a novel approach, based on Constraint Logic Programming (CLP), to predict the 3D conformation of a protein via fragments assembly. The fragments are extracted by a preprocessor-also developed for this work- from a database of known protein structures that clusters and classifies the fragments according to similarity and frequency. The problem of assembling fragments into a complete conformation is mapped to a constraint solving problem and solved using CLP. The constraint-based model uses a medium discretization degree Ca-side chain centroid protein model that offers efficiency and a good approximation for space filling. The approach adapts existing energy models to the protein representation used and applies a large neighboring search strategy. The results shows the feasibility and efficiency of the method. The declarative nature of the solution allows to include future extensions, e.g., different size fragments for better accuracy.Comment: special issue dedicated to ICLP 201

Constraint Logic Programming approach to protein structure prediction

BACKGROUND: The protein structure prediction problem is one of the most challenging problems in biological sciences. Many approaches have been proposed using database information and/or simplified protein models. The protein structure prediction problem can be cast in the form of an optimization problem. Notwithstanding its importance, the problem has very seldom been tackled by Constraint Logic Programming, a declarative programming paradigm suitable for solving combinatorial optimization problems. RESULTS: Constraint Logic Programming techniques have been applied to the protein structure prediction problem on the face-centered cube lattice model. Molecular dynamics techniques, endowed with the notion of constraint, have been also exploited. Even using a very simplified model, Constraint Logic Programming on the face-centered cube lattice model allowed us to obtain acceptable results for a few small proteins. As a test implementation their (known) secondary structure and the presence of disulfide bridges are used as constraints. Simplified structures obtained in this way have been converted to all atom models with plausible structure. Results have been compared with a similar approach using a well-established technique as molecular dynamics. CONCLUSIONS: The results obtained on small proteins show that Constraint Logic Programming techniques can be employed for studying protein simplified models, which can be converted into realistic all atom models. The advantage of Constraint Logic Programming over other, much more explored, methodologies, resides in the rapid software prototyping, in the easy way of encoding heuristics, and in exploiting all the advances made in this research area, e.g. in constraint propagation and its use for pruning the huge search space

Formation of a Unique Cluster of G-Quadruplex Structures in the HIV-1 nef Coding Region: Implications for Antiviral Activity

G-quadruplexes are tetraplex structures of nucleic acids that can form in G-rich sequences. Their presence and functional role have been established in telomeres, oncogene promoters and coding regions of the human chromosome. In particular, they have been proposed to be directly involved in gene regulation at the level of transcription. Because the HIV-1 Nef protein is a fundamental factor for efficient viral replication, infectivity and pathogenesis in vitro and in vivo, we investigated G-quadruplex formation in the HIV-1 nef gene to assess the potential for viral inhibition through G-quadruplex stabilization. A comprehensive computational analysis of the nef coding region of available strains showed the presence of three conserved sequences that were uniquely clustered. Biophysical testing proved that G-quadruplex conformations were efficiently stabilized or induced by G-quadruplex ligands in all three sequences. Upon incubation with a G-quadruplex ligand, Nef expression was reduced in a reporter gene assay and Nef-dependent enhancement of HIV-1 infectivity was significantly repressed in an antiviral assay. These data constitute the first evidence of the possibility to regulate HIV-1 gene expression and infectivity through G-quadruplex targeting and therefore open a new avenue for viral treatment. © 2013 Perrone et al

View and review on viral oncology research

To date, almost one and a half million cases of cancer are diagnosed every year in the US and nearly 560,000 Americans are expected to die of cancer in the current year, more than 1,500 people a day (data from the American Cancer Society at http://www.cancer.org/). According to the World Health Organization (WHO), roughly 20% of all cancers worldwide results from chronic infections; in particular, up to 15% of human cancers is characterized by a viral aetiology with higher incidence in Developing Countries. The link between viruses and cancer was one of the pivotal discoveries in cancer research during the past Century. Indeed, the infectious nature of specific tumors has important implications in terms of their prevention, diagnosis, and therapy. In the 21st Century, the research on viral oncology field continues to be vigorous, with new significant and original studies on viral oncogenesis and translational research from basic virology to treatment of cancer. This review will cover different viral oncology aspects, starting from the history of viral oncology and moving to the peculiar features of oncogenic RNA and DNA viruses, with a special focus on human pathogens

Davide Ferrario filme Turin : une ville en transformation

Les critiques et les chercheurs qui ont étudié le cinéma du réalisateur italien contemporain Davide Ferrario soulignent la variété de sa filmographie, aussi bien par les sujets que par les genres abordés, ce qui rend, au premier abord, sa production difficile à classer. L'étude des films de Davide Ferrario tournés à Turin s'inscrit dans la tendance de la production cinématographique italienne d'associer le nom d'un réalisateur à une ville. Un point commun des trois films réalisés à partir d'un sujet original est donc l'unité de lieu que l'on peut trouver dans chaque film et surtout l'attention particulière pour les décors l'architecture et le paysage turinois. Dans la rédaction de ce mémoire, j'aimerais montrer comment des lieux bien identifiés de la ville façonnent le scénario et la mise en scène des films de Davide Ferrario et, en même temps, essayer de comprendre comment ce réalisateur filme les changements qui ont eu lieu dans les deux dernières décennies à Turin

Belle e maledette. Come le icone del design ci affascinano ancora oggi / Beautiful and damned. How design icons still fascinate us today

The icons of contemporary design, cult objects that represent the most popular stylistic movements, nowadays increasingly appear in our homes, in our bookcases, on the desks of our offices. These objects, which have become almost a "designer's and architect’s" fetish, are flanked by as many small obsessions, manias or simple recursive approaches of their creators, established designers but human in their funny oddities. A little of all this, and the "curse" of design that makes it so fascinating and attractive, is investigated in "Maledetto Design. L’ossessione pop delle icone"

Human Papillomavirus Type Distribution and Correlation with Cyto-Histological Patterns in Women from the South of Italy

Human papillomavirus (HPV) type-specific distribution was evaluated in genital samples collected from 654 women from the South of Italy undergoing voluntary screening and correlated with cyto-histological abnormalities. HPV DNA was detected in 45.9% of the samples, 41.7% of which had multiple infection and 89.0% had high-risk HPV infection. The prevalence of HPV infection and the rate of multiple infections decreased with age, suggesting natural selection of HPV types with better fitness. In line with other Italian studies, the most common HPV types were HPV-6 and HPV-16, followed by HPV-51, HPV-31, HPV-53, and HPV-66, in women with both normal and abnormal cytology. Cervical intraepithelial lesions grade 2 or 3 were associated with high-risk HPV-16, HPV-18, HPV-31, and HPV-51 infection. These data indicate that prophylactic HPV vaccination is expected to reduce the burden of HPV-related cervical lesions in this population, but also suggest the potential utility of new vaccines with larger type coverage