1,730 research outputs found

    New Insights into the Mechanisms Underlying NEDD8 Structural and Functional Specificities

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    Ubiquitin (Ub) and ubiquitin-like (Ubl) proteins are small polypeptides that are conjugated to substrates affecting their activity and stability. Cells encode “receptors” containing Ub-/Ubl-binding domains that interpret and translate each modification into appropriate cellular responses. Among the different Ubls, NEDD8, which is the ubiquitin’s closest relative, retains many of the structural determinants that enable ubiquitin the ability to target proteins to degradation. Nevertheless, the direct involvement of NEDD8 conjugation to proteasome recruitment has been proved only in a few cases. To date, well-defined major NEDD8 substrates are primarily members of the cullin family, and cullin neddylation does not appear to mark these proteins for degradation. Various studies have demonstrated that selectivity between ubiquitin and NEDD8 is guaranteed by small but substantial differences. Nevertheless, several issues still need to be addressed, mainly concerning which interaction surfaces mediate NEDD8 function and what domains recognize them. Recently, two novel domains identified in KHNYN and N4BP1 proteins have shed new light on this research area. Here, I discuss some recent reports that contributed to shed light on the mechanisms underlining the discrimination between ubiquitin and NEDD8. Understanding the details of these molecular mechanisms represents a prominent facet for the identification of new therapeutic targets

    Performances of silicone coated high resistive bakelite RPC

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    Performances of several single gap (gas gap 2 mm) prototype Resistive Plate Chambers (RPC) made of high resistive ({\rho} \sim 1010 - 1012 {\Omega} cm) bakelite, commercially available in India have been studied in recent times. To make the inner electrode surfaces smooth, a thin coating of silicone has been applied. An efficiency > 90% and time resolution \sim 2 ns (FWHM) have been obtained for both the streamer and the avalanche mode. The induced charge distributions of those silicone coated RPC are studied and the results are presented. A numerical study on the effect of surface roughness of the resistive electrodes on the electric field of the device has been carried out using Garfield-neBEM code. A few results for a simplified model representing surface roughness, measured using a surface profilometer for the bakelite surfaces, have also been presented

    Performances of linseed oil-free bakelite RPC prototypes with cosmic ray muons

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    A comparative study has been performed on Resistive Plate Chambers (RPC) made of two different grades of bakelite paper laminates, produced and commercially available in India. The chambers, operated in the streamer mode using argon, tetrafluroethane and isobutane in 34:59:7 mixing ratio, are tested for the efficiency and the stability with cosmic rays. A particular grade of bakelite (P-120, NEMA LI-1989 Grade XXX), used for high voltage insulation in humid conditions, was found to give satisfactory performance with stable efficiency of > 96% continuously for more than 130 days. A thin coating of silicone fluid on the inner surfaces of the bakelite RPC is found to be necessary for operation of the detector.Comment: 6 figures, Presented in IX International Workshop on Resistive Plate Chamber and related Detectors-2007, TIFR, Mumbai, India, February 13-16, 200

    Binding to DPF-motif by the POB1 EH domain is responsible for POB1-Eps15 interaction

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    <p>Abstract</p> <p>Background</p> <p>Eps15 homology (EH) domains are protein interaction modules binding to peptides containing Asn-Pro-Phe (NPF) motifs and mediating critical events during endocytosis and signal transduction. The EH domain of POB1 associates with Eps15, a protein characterized by a striking string of DPF triplets, 15 in human and 13 in mouse Eps15, at the C-terminus and lacking the typical EH-binding NPF motif.</p> <p>Results</p> <p>By screening a multivalent nonapeptide phage display library we have demonstrated that the EH domain of POB1 has a different recognition specificity since it binds to both NPF and DPF motifs. The region of mouse Eps15 responsible for the interaction with the EH domain of POB1 maps within a 18 amino acid peptide (residues 623–640) that includes three DPF repeats. Finally, mutational analysis in the EH domain of POB1, revealed that several solvent exposed residues, while distal to the binding pocket, mediate specific recognition of binding partners through both hydrophobic and electrostatic contacts.</p> <p>Conclusion</p> <p>In the present study we have analysed the binding specificity of the POB1 EH domain. We show that it differs from other EH domains since it interacts with both NPF- and DPF-containing sequences. These unusual binding properties could be attributed to a different conformation of the binding pocket that allows to accommodate negative charges; moreover, we identified a cluster of solvent exposed Lys residues, which are only found in the EH domain of POB1, and influence binding to both NPF and DPF motifs. The characterization of structures of the DPF ligands described in this study and the POB1 EH domain will clearly determine the involvement of the positive patch and the rationalization of our findings.</p

    "Processo di Acquisto e soluzioni di e-Procurement in ambito B2B: il caso Italcementi / BravoSolution piattaforma EASY Supply"

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    Il lavoro svolto ha come obiettivi lo studio delle soluzioni di e-Procurement in ambito B2B, l'analisi della propensione all'uso degli strumenti di e-Sourcing nelle principali filiere industriali e da qui la focalizzazione sul settore Build. Segue la descrizione critica della soluzione offerta dalla piattaforma tecnologica di BravoSolution alle nuove esigenze di Acquisto della multinazionale Italcementi Group. Viene infine messa in evidenza l'esperienza effettiva del candidato all'interno del Team EASY Supply, gruppo dedicato alla gestione del processo di approvvigionamento on-line di Italcementi Group

    DOMINO: a database of domain–peptide interactions

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    Many protein interactions are mediated by small protein modules binding to short linear peptides. DOMINO () is an open-access database comprising more than 3900 annotated experiments describing interactions mediated by protein-interaction domains. DOMINO can be searched with a versatile search tool and the interaction networks can be visualized with a convenient graphic display applet that explicitly identifies the domains/sites involved in the interactions

    CUBAN, a Case Study of Selective Binding:Structural Details of the Discrimination between Ubiquitin and NEDD8

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    The newly identified CUBAN (Cullin binding domain associating with NEDD8) domain recognizes both ubiquitin and the ubiquitin-like NEDD8. Despite the high similarity between the two molecules, CUBAN shows a clear preference for NEDD8, free and conjugated to cullins. We previously characterized the domain structure, both alone and in complex with NEDD8. The results here reported are addressed to investigate the determinants that drive the selective binding of CUBAN towards NEDD8 and ubiquitin. The 15N HSQC NMR perturbation pattern of the labeled CUBAN domain, when combined with either NEDD8 or ubiquitin, shows a clear involvement of hydrophobic residues that characterize the early stages of these interactions. After a slow conformational selection step, hydrophobic and then neutral and polar interactions take place, which drive the correct orientation of the CUBAN domain, leading to differences in the recognition scheme of NEDD8 and ubiquitin. As a result, a cascade of induced fit steps seems to determine the structural preference shown for NEDD8 and therefore the basis of the selectivity of the CUBAN domain. Finally, molecular dynamics analysis was performed to determine by fluctuations the internal flexibility of the CUBAN/NEDD8 complex. We consider that our results, based on a structural investigation mainly focused on the early stages of the recognition, provide a fruitful opportunity to report the different behavior of the same protein with two highly similar binding partners

    A needlet-based approach to the shower-mode data analysis in the ARGO-YBJ experiment

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    The ARGO-YBJ experiment, located at the Yangbajing Cosmic Ray Laboratory (Tibet, 4300 m a.s.l., 606 g/cm2), is an EAS-array exploiting the full coverage approach at high altitude. The large field of view (2 sr) and the low energy threshold (few hundreds of GeV) result in a trigger rate of ∼3.5kHz and ∼1011EAS collected per year. Such a data set contains signals laying on different angular scales: point-like and extended gamma-ray sources, as well as large and intermediate scale cosmic-ray anisotropies. The separation of all these contributions is crucial, mostly when they overlap with each other. Needlets are a new form of spherical wavelets that have recently drawn a lot of attention in the cosmological literature, especially in connection with the analysis of CMB data. Needlets enjoy a number of important statistical and numerical properties which suggest that they can be very effective in handling cosmic-ray and gamma-ray data analysis. An unprecedented application to astroparticle physics is shown here. In particular, we focus on their use for background estimation, which is expected to be optimal or nearly-optimal in a well-defined mathematical sense, and for point-source detection. This technique is applied here to the ARGO-YBJ data set, stressing its advantages with respect to standard methods

    Elemental Analysis of Glass and Bakelite Electrodes Using PIXE Facility

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    The evolution of particle detectors dates back to the discovery of X-rays and radioactivity in 1890s. In detector history, the Resistive Plate Chambers (RPCs) are introduced in early 1980s. An RPC is a gaseous detector made up of two parallel electrodes having high resistivity like that of glass and bakelite. Currently several high energy physics experiments are using RPC-based detector system due to robustness and simplicity of construction. In each and every experiment, RPCs have to run continuously for several years. So, it demands an in-depth characterization of the electrode materials. In the present study, an elemental analysis of locally available glass and bakelite samples is done using PIXE facility available at Panjab University Cyclotron, Chandigarh. PIXE measurements are done using 2.7 MeV proton beam incident on the electrode sample target. The constituent elements present in these electrode samples are reported.Comment: 4 pages, 1 figures, 1 table; Presented in XXII DAE-BRNS High Energy Physics Symposium 201
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