4,632 research outputs found

    The M, E, and N structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles

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    Copyright @ 2008 American Society for Microbiology.The production of virus-like particles (VLPs) constitutes a relevant and safe model to study molecular determinants of virion egress. The minimal requirement for the assembly of VLPs for the coronavirus responsible for severe acute respiratory syndrome in humans (SARS-CoV) is still controversial. Recent studies have shown that SARS-CoV VLP formation depends on either M and E proteins or M and N proteins. Here we show that both E and N proteins must be coexpressed with M protein for the efficient production and release of VLPs by transfected Vero E6 cells. This suggests that the mechanism of SARS-CoV assembly differs from that of other studied coronaviruses, which only require M and E proteins for VLP formation. When coexpressed, the native envelope trimeric S glycoprotein is incorporated onto VLPs. Interestingly, when a fluorescent protein tag is added to the C-terminal end of N or S protein, but not M protein, the chimeric viral proteins can be assembled within VLPs and allow visualization of VLP production and trafficking in living cells by state-of-the-art imaging technologies. Fluorescent VLPs will be used further to investigate the role of cellular machineries during SARS-CoV egress.The University of Hong Kong and the French Ministry of Health

    Resection of phaeochromocytoma extending into the right atrium in a patient with multiple endocrine neoplasia type 2A

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    We report the first case of successful surgical resection of a malignant phaeochromocytoma with tumour extension into vena cava and right atrium in a patient with multiple endocrine neoplasia type 2A. A 21-year-old woman with genetic confirmation of multiple endocrine neoplasia type 2A syndrome was diagnosed with a very rare case of malignant phaeochromocytoma with tumour thrombus extension into vena cava and right atrium causing Budd-Chiari syndrome. It posed a challenge to the surgeons with regard to complete tumour resection and vascular control. Reviewing the limited literature, surgical resection by means of cardiopulmonary bypass with hypothermic circulatory arrest has been reported with success in phaeochromocytoma with advance vascular involvement. Adopting this approach, adrenalectomy with complete thrombus excision by inferior vena cava exploration and right atriotomy were performed successfully by a multidisciplinary team.published_or_final_versio

    Radio relics in cosmological simulations

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    Radio relics have been discovered in many galaxy clusters. They are believed to trace shock fronts induced by cluster mergers. Cosmological simulations allow us to study merger shocks in detail since the intra-cluster medium is heated by shock dissipation. Using high resolution cosmological simulations, identifying shock fronts and applying a parametric model for the radio emission allows us to simulate the formation of radio relics. We analyze a simulated shock front in detail. We find a rather broad Mach number distribution. The Mach number affects strongly the number density of relativistic electrons in the downstream area, hence, the radio luminosity varies significantly across the shock surface. The abundance of radio relics can be modeled with the help of the radio power probability distribution which aims at predicting radio relic number counts. Since the actual electron acceleration efficiency is not known, predictions for the number counts need to be normalized by the observed number of radio relics. For the characteristics of upcoming low frequency surveys we find that about thousand relics are awaiting discovery.Comment: 10 pages, 4 figures, Invited talk at the conference "Diffuse Relativistic Plasmas", Bangalore, 1-4 March 2011; in press in special issue of Journal of Astrophysics and Astronom

    Enhanced IL-6/IL-6R Signaling Promotes Growth and Malignant Properties in EBV-Infected Premalignant and Cancerous Nasopharyngeal Epithelial Cells

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    Nasopharyngeal carcinoma (NPC) is etiologically associated with Epstein-Barr virus (EBV) infection. However, the exact role of EBV in NPC pathogenesis remains elusive. Activation of signal transducer and activator of transcription 3 (STAT3) is common in human cancers including NPC and plays an important role in the pathogenesis and progression of human cancers. Interleukin-6 (IL-6), a major inflammatory cytokine, is a potent activator of STAT3. In this study, we report that EBV-infected immortalized nasopharyngeal epithelial (NPE) cells often acquire an enhanced response to IL-6-induced STAT3 activation to promote their growth and invasive properties. Interestingly, this enhanced IL-6/STAT3 response was mediated by overexpression of IL-6 receptor (IL-6R). Furthermore, IL-6R overexpression enhanced IL-6-induced STAT3 activation in uninfected immortalized NPE cells in vitro, and promoted growth and tumorigenicity of EBV-positive NPC cell line (C666-1) in vivo. Moreover, it is shown for the first time that IL-6R was overexpressed in clinical specimens of NPC. IL-6 expression could also be strongly detected in the stromal cells of NPC and a higher circulating level of IL-6 was found in the sera of advance-staged NPC patients compared to the control subjects. Therefore, IL-6R overexpression, coupled with enhanced IL-6/STAT3 signaling may facilitate the malignant transformation of EBV-infected premalignant NPE cells into cancer cells, and enhance malignant properties of NPC cells. © 2013 Zhang et al.published_or_final_versio

    Persistence of magnetic field driven by relativistic electrons in a plasma

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    The onset and evolution of magnetic fields in laboratory and astrophysical plasmas is determined by several mechanisms, including instabilities, dynamo effects and ultra-high energy particle flows through gas, plasma and interstellar-media. These processes are relevant over a wide range of conditions, from cosmic ray acceleration and gamma ray bursts to nuclear fusion in stars. The disparate temporal and spatial scales where each operates can be reconciled by scaling parameters that enable to recreate astrophysical conditions in the laboratory. Here we unveil a new mechanism by which the flow of ultra-energetic particles can strongly magnetize the boundary between the plasma and the non-ionized gas to magnetic fields up to 10-100 Tesla (micro Tesla in astrophysical conditions). The physics is observed from the first time-resolved large scale magnetic field measurements obtained in a laser wakefield accelerator. Particle-in-cell simulations capturing the global plasma and field dynamics over the full plasma length confirm the experimental measurements. These results open new paths for the exploration and modelling of ultra high energy particle driven magnetic field generation in the laboratory

    Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition

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    BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations
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