Glycoprotein L sets the neutralization profile of murid herpesvirus 4

Antibodies readily neutralize acute, epidemic viruses, but are less effective against more indolent pathogens such as herpesviruses. Murid herpesvirus 4 (MuHV-4) provides an accessible model for tracking the fate of antibody-exposed gammaherpesvirus virions. Glycoprotein L (gL) plays a central role in MuHV-4 entry: it allows gH to bind heparan sulfate and regulates fusion-associated conformation changes in gH and gB. However, gL is non-essential: heparan sulfate binding can also occur via gp70, and the gB–gH complex alone seems to be sufficient for membrane fusion. Here, we investigated how gL affects the susceptibility of MuHV-4 to neutralization. Immune sera neutralized gL− virions more readily than gL+ virions, chiefly because heparan sulfate binding now depended on gp70 and was therefore easier to block. However, there were also post-binding effects. First, the downstream, gL-independent conformation of gH became a neutralization target; gL normally prevents this by holding gH in an antigenically distinct heterodimer until after endocytosis. Second, gL− virions were more vulnerable to gB-directed neutralization. This covered multiple epitopes and thus seemed to reflect a general opening up of the gH–gB entry complex, which gL again normally restricts to late endosomes. gL therefore limits MuHV-4 neutralization by providing redundancy in cell binding and by keeping key elements of the virion fusion machinery hidden until after endocytosis

Parsing Spice Netlists Using a Typed Functional Language

International audienceParsing a Spice netlist is the first step of all circuit simulation programs. This part is usually done by low-level coding techniques in C or Fortran language. The aim of this paper is to show the usefulness of functional programming techniques to the needs of scientific computing

Biological relevance of charge transfer branching pathways in photolyases

In PhrA, a class III CPD photolyase, two branching tryptophan charge transfer pathways have been characterized in the mechanism of FAD photoreduction. To provide a molecular explanation of the charge transfer abilities of both pathways, we performed simulations where the protein motion and the positive charge are simultaneously propagated. Our computational approach reveals that one pathway drives a very fast charge transfer whereas the other pathway provides a very good thermodynamic stabilization of the positive charge. During the simulations, the positive charge firstly moves on the fast triad, allowing the stabilization of reduced FAD. After one nanosecond, we observe a nearly equal probability to find the charge at ending tryptophan of either pathway. Our results highlight the role of the protein environment, which manages the association of a kinetic and a thermodynamic pathways to trigger a fast and efficient FAD photoreduction

Study of the Oscillation Condition of Quartz Oscillators by Gyrator Transformation

International audienceThe calculation of the oscillation condition is one of the main points of oscillator analysis. Its determination in finite term allows one to calculate the steady state amplitude and frequency of the oscillator. Symbolic solutions provide an additional insight into the behavior of the circuit. As an example the sensitivity of the oscillator to parameter change can be expressed in an exact form. Numerical solutions are not as helpful as symbolic solutions in the design stage. We present a technique, based on the gyrator transformation, to set up the nonlinear equation network in a form suitable to be solved with analytical methods. We develop a symbolic program based on this technique. As an example, the symbolic program is applied to compute the exact expression of the steady state frequency and amplitude of the Van der Pol oscillator and the Colpitts oscillator

Ecological determinants of fungal diversity on dead wood in European forests

International audienceThe fine-scale ecological determinants for wood-inhabiting aphyllophoroid basidiomycetes were investigated with statistical analyses of the occurrence of fruit bodies on woody debris collected in Switzerland and Ukraine. Three substrate descriptors were considered: diameter, degree of decomposition and host tree species. By means of Multiple Regression Trees, thresholds in the response of fungal communities to these local environmental descriptors were detected. Three classes for diameter, as well as for degree of decomposition were thus delimited. They revealed the importance of very small sizes, which were not reported in the literature so far: the relevant diameter class limits were about 0.72 cm and 1.35 cm. Within the host tree species, a clear distinction between coniferous and broadleaf species was found. The next splits followed rather climatic determinants of tree distribution than taxonomical entities such as families or genera. The fidelity of the 59 fungal species to diameter classes, decomposition classes and host tree species was measured by the Dufrêne-Legendre index and only significant responses after permutation tests were retained. This brought new insights on the ecology of many wood-inhabiting aphyllophoroid basidiomycetes. Redundancy Analysis was applied to investigate the response of fungal species to diameter and degree of decomposition of woody debris from the most common host tree species, Fagus sylvatica. This direct gradient analysis made it possible to reconstruct the succession of fungal species along the wood decomposition process

Design and realisation of a 100MHz synthesis chain from an X-band reference signal

LPMO has undertaken the building of a cryogenic sapphire oscillator with the support of th french Space and Metrolgy agencies (CNES and BNM). The aim of this project is to provide a reference oscillator presenting short frequency stability better than 5.10-14 in order to fulfill reference tests requirements for spacial and metrological applications. The cryogenic oscillator can operate on different frequencies ranging from 8 to 13GHz depending on the sapphire resonator mode chosen as reference. The exact output signal frequency is not ‘a priori' known with a great accuracy due to the large relative uncertainties (of the order of 10-4) affecting the resonator frequencies theoritical determination. Then a special synthesis chain has to be designed in order to transfert the cryogenic oscillator performances to a reference signal whose frequency is fully compatible with most of Time and Frequency instrumentation. In this paper, we present the design, realization and preliminary tests of a synthesis chain generating a 100MHz signal from an X-band reference. The performances of the two realyzed prototypes will enable to transfert better than 5.10-14 short term frequency stability

Murid herpesvirus 4 infection protects mice from the development of an anti-pneumovirus vaccine-induced TH2 immunopathology

Gammaherpesvirus imprintin

Herpesvirus Glycoproteins Undergo Multiple Antigenic Changes before Membrane Fusion

Herpesvirus entry is a complicated process involving multiple virion glycoproteins and culminating in membrane fusion. Glycoprotein conformation changes are likely to play key roles. Studies of recombinant glycoproteins have revealed some structural features of the virion fusion machinery. However, how the virion glycoproteins change during infection remains unclear. Here using conformation-specific monoclonal antibodies we show in situ that each component of the Murid Herpesvirus-4 (MuHV-4) entry machinery—gB, gH/gL and gp150—changes in antigenicity before tegument protein release begins. Further changes then occurred upon actual membrane fusion. Thus virions revealed their final fusogenic form only in late endosomes. The substantial antigenic differences between this form and that of extracellular virions suggested that antibodies have only a limited opportunity to block virion membrane fusion

Interventional radiology in the management of complications after liver transplantation

The arrival of new surgical transplantation techniques, such as split living donor or auxiliary liver transplantation, have increased the incidence of vascular and biliary complications. The causes, symptoms, and diagnostic modalities of arterial, portal caval, and biliary complications are detailed. Interventional techniques, such as balloon angioplasty and stent placement in the arterial and portal tree, as well as biliary interventional techniques, are discusse