Psychosocial Stress-Induced Analgesia: An Examination of Effects on Heat Pain Threshold and Tolerance and of Neuroendocrine Mediation

Stress-induced analgesia (SIA) is an adaptive response of reduced nociception following demanding acute internal and external stressors. Although a psychobiological understanding of this phenomenon is of importance for stress-related psychiatric and pain conditions, comparably little is known about the psychobiological mechanisms of SIA in humans. The aim of this study was to investigate the effects of acute psychosocial stress on heat pain perception and its possible neuroendocrine mediation by salivary cortisol levels and α-amylase activity in healthy men. Employing an intra-individual assessment of heat pain parameters, acute psychosocial stress did not influence heat pain threshold but significantly, albeit slightly, increased heat pain tolerance. Using linear mixed-model analysis, this effect of psychosocial stress on heat pain tolerance was not mediated by increases of salivary cortisol and state anxiety levels or by the activity of α-amylase. These results show that while psychosocial stress is selectively analgesic for heat pain tolerance, this observed effect is not mediated by stress-induced increases of salivary cortisol and α-amylase activity, as proxies of both the hypothalamus-pituitary-adrenal axis and the autonomic nervous system activation

Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1

Binding of herpes simplex virus (HSV) glycoprotein D (gD) to a cell surface receptor is required to trigger membrane fusion during entry into host cells. Nectin-1 is a cell adhesion molecule and the main HSV receptor in neurons and epithelial cells. We report the structure of gD bound to nectin-1 determined by x-ray crystallography to 4.0 Å resolution. The structure reveals that the nectin-1 binding site on gD differs from the binding site of the HVEM receptor. A surface on the first Ig-domain of nectin-1, which mediates homophilic interactions of Ig-like cell adhesion molecules, buries an area composed by residues from both the gD N- and C-terminal extensions. Phenylalanine 129, at the tip of the loop connecting β-strands F and G of nectin-1, protrudes into a groove on gD, which is otherwise occupied by C-terminal residues in the unliganded gD and by N-terminal residues in the gD/HVEM complex. Notably, mutation of Phe129 to alanine prevents nectin-1 binding to gD and HSV entry. Together these data are consistent with previous studies showing that gD disrupts the normal nectin-1 homophilic interactions. Furthermore, the structure of the complex supports a model in which gD-receptor binding triggers HSV entry through receptor-mediated displacement of the gD C-terminal region

α-Herpesvirus glycoprotein D interaction with sensory neurons triggers formation of varicosities that serve as virus exit sites

α-Herpesviruses constitute closely related neurotropic viruses, including herpes simplex virus in man and pseudorabies virus (PRV) in pigs. Peripheral sensory neurons, such as trigeminal ganglion (TG) neurons, are predominant target cells for virus spread and lifelong latent infections. We report that in vitro infection of swine TG neurons with the homologous swine α-herpesvirus PRV results in the appearance of numerous synaptophysin-positive synaptic boutons (varicosities) along the axons. Nonneuronal cells that were juxtaposed to these varicosities became preferentially infected with PRV, suggesting that varicosities serve as axonal exit sites for the virus. Viral envelope glycoprotein D (gD) was found to be necessary and sufficient for the induction of varicosities. Inhibition of Cdc42 Rho GTPase and p38 mitogen-activated protein kinase signaling pathways strongly suppressed gD-induced varicosity formation. These data represent a novel aspect of the cell biology of α-herpesvirus infections of sensory neurons, demonstrating that virus attachment/entry is associated with signaling events and neuronal changes that may prepare efficient egress of progeny virus

Utilizing linked open data for web service selection and composition to support e-commerce transactions

© Springer International Publishing Switzerland 2016. Web Services (WS) have emerged during the past decades as a means for loosely coupled distributed systems to interact and communicate. Nevertheless, the abundance of services that can be retrieved online, often providing similar functionalities, can raise questions regarding the selection of the optimal service to be included in a value added composition. We propose a framework for the selection and composition of WS utilizing Linked open Data (LoD). The proposed method is based on RDF triples describing the functional and non-functional characteristics of WS. We aim at the optimal composition of services as a result of specific SPARQL queries and personalized weights for QoS criteria. Finally we utilize an approach based on the particle swarm optimization (PSO) method for the ranking of returned services

A (fascinating) litmus test for human retino-vs. non-retinotopic processing

In human vision, the optics of the eye map neighboring points of the environment onto neighboring photoreceptors in the retina. This retinotopic encoding principle is preserved in the early visual areas. Under normal viewing conditions, due to the motion of objects and to eye movements, the retinotopic representation of the environment undergoes fast and drastic shifts. Yet, perceptually our environment appears stable suggesting the existence of non-retinotopic representations in addition to the well-known retinotopic ones. Here, we present a simple psychophysical test to determine whether a given visual process is accomplished in retino-or non-retinotopic coordinates. As examples, we show that visual search and motion perception can occur within a non-retinotopic frame of reference. These findings suggest that more mechanisms than previously thought operate non-retinotopically. Whether this is true for a given visual process can easily be found out with our "litmus test.&quot

Herpes Virus Fusion and Entry: A Story with Many Characters

Herpesviridae comprise a large family of enveloped DNA viruses all of whom employ orthologs of the same three glycoproteins, gB, gH and gL. Additionally, herpesviruses often employ accessory proteins to bind receptors and/or bind the heterodimer gH/gL or even to determine cell tropism. Sorting out how these proteins function has been resolved to a large extent by structural biology coupled with supporting biochemical and biologic evidence. Together with the G protein of vesicular stomatitis virus, gB is a charter member of the Class III fusion proteins. Unlike VSV G, gB only functions when partnered with gH/gL. However, gH/gL does not resemble any known viral fusion protein and there is evidence that its function is to upregulate the fusogenic activity of gB. In the case of herpes simplex virus, gH/gL itself is upregulated into an active state by the conformational change that occurs when gD, the receptor binding protein, binds one of its receptors. In this review we focus primarily on prototypes of the three subfamilies of herpesviruses. We will present our model for how herpes simplex virus (HSV) regulates fusion in series of highly regulated steps. Our model highlights what is known and also provides a framework to address mechanistic questions about fusion by HSV and herpesviruses in general

Saliency maps for finding changes in visual scenes?

Sudden changes in the environment reliably summon attention. This rapid change detection appears to operate in a similar fashion as pop-out in visual search, the phenomenon that very salient stimuli are directly attended, independently of the number of distracting objects. Pop-out is usually explained by the workings of saliency maps, i.e., map-like representations that code for the conspicuity at each location of the visual field. While past research emphasized similarities between pop-out search and change detection, our study highlights differences between the saliency computations in the two tasks: in contrast to pop-out search, saliency computation in change detection (i) operates independently across different stimulus properties (e.g., color and orientation), and (ii) is little influenced by trial history. These deviations from pop-out search are not due to idiosyncrasies of the stimuli or task design, as evidenced by a replication of standard findings in a comparable visual-search design. To explain these results, we outline a model of change detection involving the computation of feature-difference maps, which explains the known similarities and differences with visual search

LHC1: a semiconductor pixel detector readout chip with internal, tunable delay providing a binary pattern of selected events

The Omega3/LHCl pixel detector readout chip comprises a matrix of 128 X 16 readout cells of 50 mu m X 500 mu m and peripheral functions with 4 distinct modes of initialization and operation, together more than 800 000 transistors. Each cell contains a complete chain of amplifier, discriminator with adjustable threshold and fast-OR output, a globally adjustable delay with local fine-tuning, coincidence logic and memory. Every cell can be individually addressed for electrical test and masking, First results have been obtained from electrical tests of a chip without detector as well as from source measurements, The electronic noise without detector is similar to 100 e(-) rms. The lowest threshold setting is close to 2000 e(-) and non-uniformity has been measured to be better than 450 e(-) rms at 5000 e(-) threshold. A timewalk of < 10 ns and a precision of < 6 ns rms on a delay of 2 mu s have been measured. The results may be improved by further optimization

Glycosaminoglycan Interactions in Murine Gammaherpesvirus-68 Infection

Glycosaminoglycans (GAGs) commonly participate in herpesvirus entry. They are thought to provide a reversible attachment to cells that promotes subsequent receptor binding. Murine gamma-herpesvirus-68 (MHV-68) infection of fibroblasts and epithelial cells is highly GAG-dependent. This is a function of the viral gp150, in that gp150-deficient mutants are much less GAG-dependent than wild-type. Here we show that the major MHV-68 GAG-binding protein is not gp150 but gp70, a product of ORF4. Surprisingly, ORF4-deficient MHV-68 showed normal cell binding and was more sensitive than wild-type to inhibition by soluble heparin rather than less. Thus, the most obvious viral GAG interaction made little direct contribution to infection. Indeed, a large fraction of the virion gp70 had its GAG-binding domain removed by post-translational cleavage. ORF4 may therefore act mainly to absorb soluble GAGs and prevent them from engaging gp150 prematurely. In contrast to gp70, gp150 bound poorly to GAGs, implying that it provides little in the way of adhesion. We hypothesize that it acts instead as a GAG-sensitive switch that selectively activates MHV-68 entry at cell surfaces

Identification of restriction endonuclease with potential ability to cleave the HSV-2 genome: Inherent potential for biosynthetic versus live recombinant microbicides

<p>Abstract</p> <p>Background</p> <p>Herpes Simplex virus types 1 and 2 are enveloped viruses with a linear dsDNA genome of ~120–200 kb. Genital infection with HSV-2 has been denoted as a major risk factor for acquisition and transmission of HIV-1. Developing biomedical strategies for HSV-2 prevention is thus a central strategy in reducing global HIV-1 prevalence. This paper details the protocol for the isolation of restriction endunucleases (REases) with potent activity against the HSV-2 genome and models two biomedical interventions for preventing HSV-2.</p> <p>Methods and Results</p> <p>Using the whole genome of HSV-2, 289 REases and the bioinformatics software Webcutter2; we searched for potential recognition sites by way of genome wide palindromics. REase application in HSV-2 biomedical therapy was modeled concomitantly. Of the 289 enzymes analyzed; 77(26.6%) had potential to cleave the HSV-2 genome in > 100 but < 400 sites; 69(23.9%) in > 400 but < 700 sites; and the 9(3.1%) enzymes: BmyI, Bsp1286I, Bst2UI, BstNI, BstOI, EcoRII, HgaI, MvaI, and SduI cleaved in more than 700 sites. But for the 4: PacI, PmeI, SmiI, SwaI that had no sign of activity on HSV-2 genomic DNA, all 130(45%) other enzymes cleaved < 100 times. In silico palindromics has a PPV of 99.5% for in situ REase activity (2) Two models detailing how the REase EcoRII may be applied in developing interventions against HSV-2 are presented: a nanoparticle for microbicide development and a "recombinant lactobacillus" expressing cell wall anchored receptor (truncated nectin-1) for HSV-2 plus EcoRII.</p> <p>Conclusion</p> <p>Viral genome slicing by way of these bacterially- derived R-M enzymatic peptides may have therapeutic potential in HSV-2 infection; a cofactor for HIV-1 acquisition and transmission.</p