Sequence-based study of two related proteins with different folding behaviors

ZSPA-1 is an engineered protein that binds to its parent, the three-helix-bundle Z domain of staphylococcal protein A. Uncomplexed ZSPA-1 shows a reduced helix content and a melting behavior that is less cooperative, compared with the wild-type Z domain. Here we show that the difference in folding behavior between these two sequences can be partly understood in terms of an off-lattice model with 5-6 atoms per amino acid and a minimalistic potential, in which folding is driven by backbone hydrogen bonding and effective hydrophobic attraction.Comment: 12 pages, 5 figure

Beyond e-learning: from blended methodology to transmedia education

Nowadays, at the time of convergence culture, social network, and transmedia storytelling – when social interactions are constantly remediated – e-learning, especially in universities, should be conceived as a sharing educational activity. Different learning experiences should become smoother and able to fade out the closed learning environments (as software platform and classrooms (either virtual or not)). In this paper, we will show some experiences of the Communication Sciences degree program of the University of Cagliari, which is supplied through an e-learning method. In the ten years since its foundation, the approach has evolved from a blended learning with two kinds of traditional activity (online activities and face-to-face lessons) to a much more dynamic learning experience. Many new actors (communication companies, local government, public-service corporations, new media and social media) – indeed – have been involved in educational and teaching process. But also these processes changed: collaborative working, new media comprehension, self-guided problem solving are examples of the new literacies and approaches that can be reached as new learning objectives

Interazioni tra fumi e sistemi sprinkler: analisi fluidodinamica durante un incendio

Gli incendi in galleria costituiscono uno degli scenari incidentali di maggior rischio e sono stati oggetto di ampi studi in letteratura, volti ad indagarne lo sviluppo o l’influenza di vari parametri, come ad esempio l’effetto delle ostruzioni sulla velocità critica di ventilazione. Uno sviluppo minore è invece riscontrabile per quanto riguarda l’utilizzo e gli effetti di impianti di tipo sprinkler per migliorare la sicurezza dei tunnel stradali. Un esempio recente è costituito dallo studio di Zheng e Ingason, in cui l’impiego di sprinkler è stato testato su una riproduzione in scala di una galleria stradale. Questo studio si propone di indagare l’interazione tra i fumi e i sistemi antincendio fissi ad acqua in galleria, problema che risulta essere tuttora non completamente risolto

Monte Carlo Update for Chain Molecules: Biased Gaussian Steps in Torsional Space

We develop a new elementary move for simulations of polymer chains in torsion angle space. The method is flexible and easy to implement. Tentative updates are drawn from a (conformation-dependent) Gaussian distribution that favors approximately local deformations of the chain. The degree of bias is controlled by a parameter b. The method is tested on a reduced model protein with 54 amino acids and the Ramachandran torsion angles as its only degrees of freedom, for different b. Without excessive fine tuning, we find that the effective step size can be increased by a factor of three compared to the unbiased b=0 case. The method may be useful for kinetic studies, too.Comment: 14 pages, 4 figure

Preliminary CFD analysis of a ventilated chamber for candles testing

As candles have grown in popularity with consumers over the last few years, so has the potential safety concern with their use in indoor environments. Carbon monoxide, particulate matter and different volatile and semi-volatile species can be found in candles emissions. Currently it is not possible to predict theoretically which emissions will be produced by a specific candle and in order to quantify real emissions is still necessary to proceed with experimental tests. A common way to quantify released pollutants is to burn candles in a well-controlled environment, such as a laboratory-scale test chambers. Obviously, it is required that these chambers are able to reproduce the environmental combustion regime of the candles, so as to guarantee that an equal level of emissions is produced and measured. Another crucial point is related to the measurements themselves: generally, air quality is measured in a single point inside the chamber with the assumption that the air and the exhausts in that point are representative of the whole ambient. This work aims to reproduce one of these chambers by means of a CFD (Computational Fluid Dynamics) model, with the purpose of obtaining an adequate tool to analyze and design more efficient test chambers. A comparison with an ad hoc experiment is performed to validate the CFD model

The Young Classic

2017 Jan Rehner Writing Prize Finalists, 4th Year Honourable MentionWRIT 470

The TRiC/CCT chaperone is implicated in Alzheimer's disease based on patient GWAS and an RNAi screen in Aβ-expressing Caenorhabditis elegans.

The human Aβ peptide causes progressive paralysis when expressed in the muscles of the nematode worm, C. elegans. We have exploited this model of Aβ toxicity by carrying out an RNAi screen to identify genes whose reduced expression modifies the severity of this locomotor phenotype. Our initial finding was that none of the human orthologues of these worm genes is identical with the genome-wide significant GWAS genes reported to date (the "white zone"); moreover there was no identity between worm screen hits and the longer list of GWAS genes which included those with borderline levels of significance (the "grey zone"). This indicates that Aβ toxicity should not be considered as equivalent to sporadic AD. To increase the sensitivity of our analysis, we then considered the physical interactors (+1 interactome) of the products of the genes in both the worm and the white+grey zone lists. When we consider these worm and GWAS gene lists we find that 4 of the 60 worm genes have a +1 interactome overlap that is larger than expected by chance. Two of these genes form a chaperonin complex, the third is closely associated with this complex and the fourth gene codes for actin, the major substrate of the same chaperonin

Universality and diversity of folding mechanics for three-helix bundle proteins

In this study we evaluate, at full atomic detail, the folding processes of two small helical proteins, the B domain of protein A and the Villin headpiece. Folding kinetics are studied by performing a large number of ab initio Monte Carlo folding simulations using a single transferable all-atom potential. Using these trajectories, we examine the relaxation behavior, secondary structure formation, and transition-state ensembles (TSEs) of the two proteins and compare our results with experimental data and previous computational studies. To obtain a detailed structural information on the folding dynamics viewed as an ensemble process, we perform a clustering analysis procedure based on graph theory. Moreover, rigorous pfold analysis is used to obtain representative samples of the TSEs and a good quantitative agreement between experimental and simulated Fi-values is obtained for protein A. Fi-values for Villin are also obtained and left as predictions to be tested by future experiments. Our analysis shows that two-helix hairpin is a common partially stable structural motif that gets formed prior to entering the TSE in the studied proteins. These results together with our earlier study of Engrailed Homeodomain and recent experimental studies provide a comprehensive, atomic-level picture of folding mechanics of three-helix bundle proteins.Comment: PNAS, in press, revised versio

Fibril elongation mechanisms of HET-s prion-forming domain: Topological evidence for growth polarity

The prion-forming C-terminal domain of the fungal prion HET-s forms infectious amyloid fibrils at physiological pH. The conformational switch from the non-prion soluble form to the prion fibrillar form is believed to have a functional role, since HET-s in its prion form participates in a recognition process of different fungal strains. Based on the knowledge of the high-resolution structure of HET-s(218-289) (the prion forming-domain) in its fibrillar form, we here present a numerical simulation of the fibril growth process which emphasizes the role of the topological properties of the fibrillar structure. An accurate thermodynamic analysis of the way an intervening HET-s chain is recruited to the tip of the growing fibril suggests that elongation proceeds through a dock and lock mechanism. First, the chain docks onto the fibril by forming the longest $\beta$-strands. Then, the re-arrangement in the fibrillar form of all the rest of molecule takes place. Interestingly, we predict also that one side of the HET-s fibril is more suitable for substaining its growth with respect to the other. The resulting strong polarity of fibril growth is a consequence of the complex topology of HET-s fibrillar structure, since the central loop of the intervening chain plays a crucially different role in favouring or not the attachment of the C-terminus tail to the fibril, depending on the growth side.Comment: 16 pages, 10 figure