Epstein-Barr Virus Infection of CR2-Transfected Epithelial Cells Reveals the Presence of MHC Class II on the Virion

AbstractEpithelial cell lines transfected with the Epstein-Barr virus (EBV) receptor CR2 are susceptible to infection by EBV. Following infection with certain EBV strains we found that these cells became positive for MHC class II. The class II was confirmed as being of viral and not target cell origin by immunostaining with HLA-specific monoclonal antibodies. Electron microscopic immunogold staining confirmed the presence of MHC class II on the surface of the virion. While some MHC class I was also found on the EB virion, other cell surface molecules were absent. Dual color immunofluorescence and confocal microscopy analysis demonstrated colocalization of class II with EBV-encoded structural proteins (MA and VCA) in infected epithelial cells. However, preincubation of EBV with antibodies against either MHC class I or MHC class II failed to affect either EBV binding or EBV infection. The presence of MHC on the surface of the EB virion may be a consequence of the intracellular pathways through which productive virus exits from the cell and may influence the target cell tropism of EBV

Deinstitutionalization: A Review of the Literature with Implication for Social Work Training and Practice in Rural Areas

The manuscript reviews the social, legal, and political background of the deinstitutionalization movement, reviews successful programs for deinstitutionalized chronic mental patients in the major problem areas of socialization skills training, supportive living, interventions with families, vocational rehabilitation, and medication monitoring. Problems which prevent the successful replication of these programs in rural areas, such as differing characteristics of rural and urban clients, distance and travel, and staff attitudes are discussed. Implications for social work training and practice in rural areas include the increased need for paraprofessional staff development and supervision skills, ability to utilize and mobilize existing community helping networks, and training in behavior modification techniques

Pathogens best paper awards for 2015

Pathogens is instituting annual awards to recognize the most outstanding papers in the areas of all aspects of pathogens and pathogen-host interactions published in Pathogens. We are pleased to announce the recipients of the first “Pathogens Best Paper Awards”. Nominations were selected by the Editor-in-Chief and several Editorial Board members of Pathogens from all original research articles published in 2013 or 2014. We are pleased to announce that the following three papers were chosen to receive “Pathogens Best Paper Awards” for 2015. I congratulate all of the authors and thank them for their significant and important contributions to the field of pathogens. I also thank the members of the Selection Committee for their efforts

The Transmembrane Domains of the EBV-Encoded Latent Membrane Protein 1 (LMP1) Variant CAO Regulate Enhanced Signalling Activity

AbstractSequence variants of the Epstein–Barr virus (EBV)-encoded latent membrane protein-1 (LMP1) have been reported in association with EBV-linked malignancies but little is known about their effects on signalling pathways and phenotype. We have examined the ability of the nasopharyngeal carcinoma (NPC)-derived variant, CAO-LMP1 to activate the transcription factors NF-κB and AP-1 in epithelial cells. In this study, transient expression of CAO-LMP1 was found to activate higher levels of NF-κB and AP-1 than the prototype B95.8-LMP1 in human embryonic kidney (HEK) 293 cells and SV40-transformed keratinocytes (SVK). In addition, pulse–chase analysis revealed that CAO-LMP1 has a longer half-life than B95.8-LMP1. Chimera studies localised these phenomena to the transmembrane domains of CAO-LMP1, suggesting that this enhanced signalling capacity may be a consequence of its prolonged half-life. The ability of CAO-LMP1 to activate higher levels of NF-κB and AP-1 may contribute to its potent transforming properties

CD40 ligand induced cytotoxicity in carcinoma cells is enhanced by inhibition of metalloproteinase cleavage and delivery via a conditionally-replicating adenovirus

Background CD40 and its ligand (CD40L) play a critical role in co-ordinating immune responses. CD40 is also expressed in lymphoid malignancies and a number of carcinomas. In carcinoma cells the physiological outcome of CD40 ligation depends on the level of receptor engagement with low levels promoting cell survival and high levels inducing cell death. The most profound induction of cell death in carcinoma cells is induced by membrane-bound rather than recombinant soluble CD40L, but like other TNF family ligands, it is cleaved from the membrane by matrix metalloproteinases. Results We have generated a replication-deficient adenovirus expressing a mutant CD40L that is resistant to metalloproteinase cleavage such that ligand expression is retained at the cell membrane. Here we show that the mutated, cleavage-resistant form of CD40L is a more potent inducer of apoptosis than wild-type ligand in CD40-positive carcinoma cell lines. Since transgene expression via replication-deficient adenovirus vectors in vivo is low, we have also engineered a conditionally replicating E1A-CR2 deleted adenovirus to express mutant CD40L, resulting in significant amplification of ligand expression and consequent enhancement of its therapeutic effect. Conclusions Combined with numerous studies demonstrating its immunotherapeutic potential, these data provide a strong rationale for the exploitation of the CD40-CD40L pathway for the treatment of solid tumours

PASSIVE SUPPRESSION OF AEROELASTIC INSTABILITIES OF IN-FLOW WINGS BY TARGETED ENERGY TRANSFERS TO LIGHTWEIGHT ESSENTIALLY NONLINEAR ATTACHMENTS

Theoretical and experimental suppression of aeroelastic instabilities by means of broadband passive targeted energy transfers has been recently studied. A single-degree-offreedom (SDOF) nonlinear energy sink (NES) was coupled to a 2-DOF rigid wing modeled in the low-speed, subsonic regime with quasi-steady aerodynamic theory. The nonlinear attachment was designed and optimized to suppress the critical nonlinear modal energy exchanges between the flow and the (pitch and heave) wing modes, thus suppressing the (transient) triggering mechanism of aeroelastic instability. We performed bifurcation analysis to find regions of robust passive aeroelastic suppression in parameter space. Then, we employed multi-degreeof-freedom nonlinear energy sinks (MDOF NESs) to improve robustness of the aeroelastic instability suppression. Bifurcation analysis by a numerical continuation technique demonstrated that controlling the occurrence of a limit point cycle (LPC or saddle-node) bifurcation point above a Hopf bifurcation point is crucial to enhancing suppression robustness. MDOF NESs not only can enhance robustness of suppression against even strong gust-like disturbances, but they require lower NES mass compared to SDOF NES designs. The validity of the theoretical findings was proven by a series of wind tunnel experiments

Upregulation of Id1 by Epstein-Barr Virus-encoded LMP1 confers resistance to TGFβ-mediated growth inhibition

BACKGROUND: Epstein-Barr virus (EBV)-encoded LMP1 protein is commonly expressed in nasopharyngeal carcinoma (NPC). LMP1 is a prime candidate for driving tumourigenesis given its ability to activate multiple signalling pathways and to alter the expression and activity of variety of downstream targets. Resistance to TGFβ-mediated cytostasis is one of the growth transforming effects of LMP1. Of the downstream targets manipulated by LMP1, the induction of Id1 and inactivation of Foxo3a appear particularly relevant to LMP1-mediated effects. Id1, a HLH protein is implicated in cell transformation and plays a role in cell proliferation, whilst Foxo3a, a transcription factor controls cell integrity and homeostasis by regulating apoptosis. The mechanism(s) by which LMP1 induces these effects have not been fully characterised. RESULTS: In this study, we demonstrate that the ability of LMP1 to induce the phosphorylation and inactivation of Foxo3a is linked to the upregulation of Id1. Furthermore, we show that the induction of Id1 is essential for the transforming function of LMP1 as over-expression of Id1 increases cell proliferation, attenuates TGFβ-SMAD-mediated transcription and renders cells refractory to TGFβ-mediated cytostasis. Id1 silencing in LMP1-expressing epithelial cells abolishes the inhibitory effect of LMP1 on TGFβ-mediated cell growth arrest and reduces the ability of LMP1 to attenuate SMAD transcriptional activity. In response to TGFβ stimulation, LMP1 does not abolish SMAD phosphorylation but inhibits p21 protein expression. In addition, we found the induction of Id1 in LMP1-expressing cells upon stimulation by TGFβ. We provide evidence that LMP1 suppresses the transcriptional repressor ATF3, possibly leading to the TGFβ-induced Id1 upregulation. CONCLUSION: The current data provide novel information regarding the mechanisms by which LMP1 suppresses TGFβ-induced cytostasis, highlighting the importance of Id1 in LMP1 mediated cell transformatio

The Electron Scattering Region in Seyfert Nuclei

The electron scattering region (ESR) is one of important ingredients in Seyfert nuclei because it makes possible to observe the hidden broad line region (hereafter HBLR) in some type 2 Seyfert nuclei (hereafter S2s). However, little is known about its physical and geometrical properties. Using the number ratio of S2s with and without HBLR, we investigate statistically where the ESR is in Seyfert nuclei. Our analysis suggests that the ESR is located at radius between $\sim$ 0.01 pc and $\sim$ 0.1 pc from the central engine. We also discuss a possible origin of the ESR briefly.Comment: 5 pages and 1 figure. The Astrophysical Journal (Letters), in pres

Gender Specific Disruptions in Emotion Processing in Younger Adults with Depression

Background: One of the principal theories regarding the biological basis of major depressive disorder (MDD) implicates a dysregulation of emotion-processing circuitry. Gender differences in how emotions are processed and relative experience with emotion processing might help to explain some of the disparities in the prevalence of MDD between women and men. This study sought to explore how gender and depression status relate to emotion processing. Methods: This study employed a 2 (MDD status) × 2 (gender) factorial design to explore differences in classifications of posed facial emotional expressions (N=151). Results: For errors, there was an interaction between gender and depression status. Women with MDD made more errors than did nondepressed women and men with MDD, particularly for fearful and sad stimuli (Ps Ps P=.01). Men with MDD, conversely, performed similarly to control men (P=.61). Conclusions: These results provide novel and intriguing evidence that depression in younger adults (years) differentially disrupts emotion processing in women as compared to men. This interaction could be driven by neurobiological and social learning mechanisms, or interactions between them, and may underlie differences in the prevalence of depression in women and men. Depression and Anxiety, 2009. Published 2008 Wiley-Liss, Inc