The Role of Nucleobase Interactions in RNA Structure and Dynamics

The intricate network of interactions observed in RNA three-dimensional structures is often described in terms of a multitude of geometrical properties, including helical parameters, base pairing/stacking, hydrogen bonding and backbone conformation. We show that a simple molecular representation consisting in one oriented bead per nucleotide can account for the fundamental structural properties of RNA. In this framework, canonical Watson-Crick, non-Watson-Crick base-pairing and base-stacking interactions can be unambiguously identified within a well-defined interaction shell. We validate this representation by performing two independent, complementary tests. First, we use it to construct a sequence-independent, knowledge-based scoring function for RNA structural prediction, which compares favorably to fully atomistic, state-of-the-art techniques. Second, we define a metric to measure deviation between RNA structures that directly reports on the differences in the base\u2013base interaction network. The effectiveness of this metric is tested with respect to the ability to discriminate between structurally and kinetically distant RNA conformations, performing better compared to standard techniques. Taken together, our results suggest that this minimalist, nucleobase-centric representation captures the main interactions that are relevant for describing RNA structure and dynamics

The influence of spatial distribution and work organization on the effectiveness of teamwork in an innovative multidisciplinary project

The aim of this paper is to investigate and define the type of teamwork that best fits along various phases of innovation projects based on design thinking process.Within the context of Innovation 4 Change program, the typical phases of a design thinking project havebeen analysedby means of a macro methodology matrix based on twocore variables: spatial distribution and internal organization of team members. Every single team member was asked, based on his experience, what is the most effective combination for teamwork

Febrile rhabdomyolysis of unknown origin in refugees coming from West Africa through the Mediterranean

Abstract Objectives Cases of undiagnosed severe febrile rhabdomyolysis in refugees coming from West Africa, mainly from Nigeria, has been observed since May 2014. The aim of this study was to describe this phenomenon. Methods This was a multicentre retrospective observational study of cases of febrile rhabdomyolysis reported from May 2014 to December 2016 in 12 Italian centres. Results A total of 48 cases were observed, mainly in young males. The mean time interval between the day of departure from Libya and symptom onset was 26.2 days. An average 8.3 further days elapsed before medical care was sought. All patients were hospitalized with fever and very intense muscle aches. Creatine phosphokinase, aspartate aminotransferase, and lactate dehydrogenase values were abnormal in all cases. The rhabdomyolysis was ascribed to an infective agent in 16 (33.3%) cases. In the remaining cases, the aetiology was undefined. Four out of seven patients tested had sickle cell trait. No alcohol abuse or drug intake was reported, apart from a single reported case of khat ingestion. Conclusions The long incubation period does not support a mechanical cause of rhabdomyolysis. Furthermore, viral infections such as those caused by coxsackievirus are rarely associated with such a severe clinical presentation. It is hypothesized that other predisposing conditions like genetic factors, unknown infections, or unreported non-conventional remedies may be involved. Targeted surveillance of rhabdomyolysis cases is warranted

Health and nutrition studies related to cereal biodiversity: a participatory multi-actor literature review approach

Recently, a large and growing body of literature has investigated the health potential of different wheat species. In particular, a considerable number of studies dealing with nutritional aspects has grown up around the theme of the recovery of ancient wheat varieties (species that have remained unchanged over the last hundred years). According to several studies, indeed, ancient varieties present a healthier nutritional profile than modern ones. In the framework of the European project "CERERE, CEreal REnaissance in Rural Europe: embedding diversity in organic and low-input food systems", this paper aimed to review recent research on the issue of health and nutritional cereal systems by adopting an innovative and participatory multi-actor approach which involved practitioners along with researchers. The participatory approach is the main innovation and peculiarity of this literature review. Nevertheless, the review highlights the many positive effects derived from eating whole and ancient grains such as a significant reduction in the risk of chronic diseases such as cancer, cardiovascular disease, and also a more favorable long-term weight management and increase in satiety. This review may be considered as a fruitful starting point that integrates research results to foster current and future healthier and sustainable practices in cereal systems

COVID-19 in the tonsillectomised population

Objective: Interactions between SARS-CoV-2 and pharyngeal associated lymphoid tissue are thought to influence the manifestations of COVID-19. We aimed to determine whether a previous history of tonsillectomy, as a surrogate indicator of a dysfunctional pharyngeal associated lymphoid tissue, could predict the presentation and course of COVID-19. Methods: Multicentric cross-sectional observational study involving seven hospitals in Northern and Central Italy. Data on the clinical course and signs and symptoms of the infection were collected from 779 adults who tested positive for SARS-CoV-2, and analysed in relation to previous tonsillectomy, together with demographic and anamnestic data. Results: Patients with previous tonsillectomy showed a greater risk of fever, temperature higher than 39°C, chills and malaise. No significant differences in hospital admissions were found. Conclusions: A previous history of tonsillectomy, as a surrogate indicator of immunological dysfunction of the pharyngeal associated lymphoid tissue, could predict a more intense systemic manifestation of COVID-19. These results could provide a simple clinical marker to discriminate suspected carriers and to delineate more precise prognostic models

Quantum ESPRESSO: a modular and open-source software project for quantum simulations of materials

Quantum ESPRESSO is an integrated suite of computer codes for electronic-structure calculations and materials modeling, based on density-functional theory, plane waves, and pseudopotentials (norm-conserving, ultrasoft, and projector-augmented wave). Quantum ESPRESSO stands for "opEn Source Package for Research in Electronic Structure, Simulation, and Optimization". It is freely available to researchers around the world under the terms of the GNU General Public License. Quantum ESPRESSO builds upon newly-restructured electronic-structure codes that have been developed and tested by some of the original authors of novel electronic-structure algorithms and applied in the last twenty years by some of the leading materials modeling groups worldwide. Innovation and efficiency are still its main focus, with special attention paid to massively-parallel architectures, and a great effort being devoted to user friendliness. Quantum ESPRESSO is evolving towards a distribution of independent and inter-operable codes in the spirit of an open-source project, where researchers active in the field of electronic-structure calculations are encouraged to participate in the project by contributing their own codes or by implementing their own ideas into existing codes.Comment: 36 pages, 5 figures, resubmitted to J.Phys.: Condens. Matte

Monitoring and predicting the risk of violence in residential facilities. No difference between patients with history or with no history of violence

none34noopende Girolamo, Giovanni; Buizza, Chiara; Sisti, Davide; Ferrari, Clarissa; Bulgari, Viola; Iozzino, Laura; Boero, Maria Elena; Cristiano, Giuseppe; De Francesco, Alessandra; Giobbio, Gian Marco; Maggi, Paolo; Rossi, Giuseppe; Segalini, Beatrice; Candini, Valentina; Andreose, Suor; Basso, Pasquale; Beneduce, Rossella; Bertolotti, Pietro; Braida, Vanda; Bonelli, Marina; Bongiorno, Fanny; Bussi, Riccardo; Castagno, Elisa; Dominicis, Fabio; Ghersi, Loredana; Greppo, Stefania; Sodano, Alessandro Jaretti; Leporatti, Massimo; Presti, Eleonora Lo; Milone, Valeria; Panigada, Fausto; Pasquadibisceglie, Livia; Rigamonti, Danilo; Rillosi, Lucianade Girolamo, Giovanni; Buizza, Chiara; Sisti, Davide; Ferrari, Clarissa; Bulgari, Viola; Iozzino, Laura; Boero, Maria Elena; Cristiano, Giuseppe; De Francesco, Alessandra; Giobbio, Gian Marco; Maggi, Paolo; Rossi, Giuseppe; Segalini, Beatrice; Candini, Valentina; Andreose, Suor; Basso, Pasquale; Beneduce, Rossella; Bertolotti, Pietro; Braida, Vanda; Bonelli, Marina; Bongiorno, Fanny; Bussi, Riccardo; Castagno, Elisa; Dominicis, Fabio; Ghersi, Loredana; Greppo, Stefania; Sodano, Alessandro Jaretti; Leporatti, Massimo; Presti, Eleonora Lo; Milone, Valeria; Panigada, Fausto; Pasquadibisceglie, Livia; Rigamonti, Danilo; Rillosi, Lucian

Multiple Routes and Milestones in the Folding of HIV–1 Protease Monomer

Proteins fold on a time scale incompatible with a mechanism of random search in conformational space thus indicating that somehow they are guided to the native state through a funneled energetic landscape. At the same time the heterogeneous kinetics suggests the existence of several different folding routes. Here we propose a scenario for the folding mechanism of the monomer of HIV–1 protease in which multiple pathways and milestone events coexist. A variety of computational approaches supports this picture. These include very long all-atom molecular dynamics simulations in explicit solvent, an analysis of the network of clusters found in multiple high-temperature unfolding simulations and a complete characterization of free-energy surfaces carried out using a structure-based potential at atomistic resolution and a combination of metadynamics and parallel tempering. Our results confirm that the monomer in solution is stable toward unfolding and show that at least two unfolding pathways exist. In our scenario, the formation of a hydrophobic core is a milestone in the folding process which must occur along all the routes that lead this protein towards its native state. Furthermore, the ensemble of folding pathways proposed here substantiates a rational drug design strategy based on inhibiting the folding of HIV–1 protease