Architecturally diverse proteins converge on an analogous mechanism to inactivate Uracil-DNA glycosylase

Uracil-DNA glycosylase (UDG) compromises the replication strategies of diverse viruses from unrelated lineages. Virally encoded proteins therefore exist to limit, inhibit or target UDG activity for proteolysis. Viral proteins targeting UDG, such as the bacteriophage proteins ugi, and p56, and the HIV-1 protein Vpr, share no sequence similarity, and are not structurally homologous. Such diversity has hindered identification of known or expected UDG-inhibitory activities in other genomes. The structural basis for UDG inhibition by ugi is well characterized; yet, paradoxically, the structure of the unbound p56 protein is enigmatically unrevealing of its mechanism. To resolve this conundrum, we determined the structure of a p56 dimer bound to UDG. A helix from one of the subunits of p56 occupies the UDG DNA-binding cleft, whereas the dimer interface forms a hydrophobic box to trap a mechanistically important UDG residue. Surprisingly, these p56 inhibitory elements are unexpectedly analogous to features used by ugi despite profound architectural disparity. Contacts from B-DNA to UDG are mimicked by residues of the p56 helix, echoing the role of ugi’s inhibitory beta strand. Using mutagenesis, we propose that DNA mimicry by p56 is a targeting and specificity mechanism supporting tight inhibition via hydrophobic sequestration

Structure of a bacterial type IV secretion core complex at subnanometre resolution

Type IV secretion (T4S) systems are able to transport DNAs and/or proteins through the membranes of bacteria. They form large multiprotein complexes consisting of 12 proteins termed VirB1-11 and VirD4. VirB7, 9 and 10 assemble into a 1.07 MegaDalton membrane-spanning core complex (CC), around which all other components assemble. This complex is made of two parts, the O-layer inserted in the outer membrane and the I-layer inserted in the inner membrane. While the structure of the O-layer has been solved by X-ray crystallography, there is no detailed structural information on the I-layer. Using high-resolution cryo-electron microscopy and molecular modelling combined with biochemical approaches, we determined the I-layer structure and located its various components in the electron density. Our results provide new structural insights on the CC, from which the essential features of T4S system mechanisms can be derived

Dynamics of Fattening and Thinning 2D Sessile Droplets

We investigate the dynamics of a droplet on a planar substrate as the droplet volume changes dynamically due to liquid being pumped in or out through a pore. We adopt a diffuse-interface formulation which is appropriately modified to account for a localized inflow–outflow boundary condition (the pore) at the bottom of the droplet, hence allowing to dynamically control its volume, as the droplet moves on a flat substrate with a periodic chemical pattern. We find that the droplet undergoes a stick–slip motion as the volume is increased (fattening droplet) which can be monitored by tracking the droplet contact points. If we then switch over to outflow conditions (thinning droplet), the droplet follows a different path (i.e., the distance of the droplet midpoint from the pore location evolves differently), giving rise to a hysteretic behavior. By means of geometrical arguments, we are able to theoretically construct the full bifurcation diagram of the droplet equilibria (positions and droplet shapes) as the droplet volume is changed, finding excellent agreement with time-dependent computations of our diffuse-interface model

Use of an Online Platform to Evaluate the Impact of Social Distancing Measures on Psycho-Physical Well-Being in the COVID-19 Era

Background: The SARS-CoV-2 pandemic (Severe Acute Respiratory Syndrome Coronavirus 2) and the worldwide health crisis have significantly changed both people's habits and lifestyles. Most of the studies found in the literature were carried out on specific professional categories in the socio-health sector, taking into consideration psychological disorders in relation to work. The purpose of this study was to analyze the psychological impact on a portion of the normal population subjected to lockdown. Methods: A questionnaire was distributed in the period between 23 March 2020 and 18 May 2020 (during Italian lockdown) using an online platform. The scales GAD-7, IES-r, PHQ-9 and MANSA were used to investigate the level of anxiety, the presence of post-traumatic stress disorder, the severity of depression and the perceived quality of life, respectively. Results: Four hundred and eight Italian subjects responded. Females and younger people were more affected by anxiety and depression. Post-traumatic stress disorder affected about 40% of the population sample, significantly young people and women, thus attesting to an important psychopathological response. About one-fifth of the sample population recorded an unsatisfactory quality of life. Conclusions: The results highlight the need to set up preventive interventions (primary and secondary), trying to focus on the most fragile group of subjects from a psychosocial point of view, in order to obtain a significant reduction in psychophysical damage in terms of relapses and outcomes

A Design Space Exploration Framework for ANN-Based Fault Detection in Hardware Systems

This work presents a design exploration framework for developing a high level Artificial Neural Network (ANN) for fault detection in hardware systems. ANNs can be used for fault detection purposes since they have excellent characteristics such as generalization capability, robustness, and fault tolerance. Designing an ANN in order to be used for fault detection purposes includes different parameters. Through this work, those parameters are presented and analyzed based on simulations. Moreover, after the development of the ANN, in order to evaluate it, a case study scenario based on Networks on Chip is used for detection of interrouter link faults. Simulation results with various synthetic traffic models show that the proposed work can detect up to 96–99% of interrouter link faults with a delay less than 60 cycles. Added to this, the size of the ANN is kept relatively small and they can be implemented in hardware easily. Synthesis results indicate an estimated amount of 0.0523 mW power consumption per neuron for the implemented ANN when computing a complete cycle

The Circumstellar Environment of High-Mass Protostellar Objects: IV. C17O Observations and Depletion

We observe 84 candidate young high-mass sources in the rare isotopologues C17O and C18O to investigate whether there is evidence for depletion (freeze-out) towards these objects. Observations of the J=2-1 transitions of C18O and C17O are used to derive the column densities of gas towards the sources and these are compared with those derived from submillimetre continuum observations. The derived fractional abundance suggests that the CO species show a range of degrees of depletion towards the objects. We then use the radiative transfer code RATRAN to model a selection of the sources to confirm that the spread of abundances is not a result of assumptions made when calculating the column densities. We find a range of abundances of C17O that cannot be accounted for by global variations in either the temperature or dust properties and so must reflect source to source variations. The most likely explanation is that different sources show different degrees of depletion of the CO. Comparison of the C17O linewidths of our sources with those of CS presented by other authors reveal a division of the sources into two groups. Sources with a CS linewidth >3 km/s have low abundances of C17O while sources with narrower CS lines have typically higher C17O abundances. We suggest that this represents an evolutionary trend. Depletion towards these objects shows that the gas remains cold and dense for long enough for the trace species to deplete. The range of depletion measured suggests that these objects have lifetimes of 2-4x10^5 years.Comment: 18 pages. Accepted for publication in Astronomy & Astrophysic

A Gas Leak Rate Measurement System for the ATLAS MUON BIS-Monitored Drift Tubes

A low-cost, reliable and precise system developed for the gas leak rate measurement of the BIS-Monitored Drift Tubes (MDTs) for the ATLAS Muon Spectrometer is presented. In order to meet the BIS-MDT mass production rate, a total number of 100 tubes are tested simultaneously in this setup. The pressure drop of each one of the MDT is measured, within a typical time interval of 48 hours, via a differential manometer comparing with the pressure of a gas tight reference tube. The precision of the method implemented is based on the system temperature homogeneity, with accuracy of ÄT = 0.3 oC. For this reason, two thermally isolated boxes are used testing 50 tubes each of them, to achieve high degree of temperature uniformity and stability. After measuring several thousands of the MDTs, the developed system is confirmed to be appropriate within the specifications for testing the MDTs during the mass production