42 research outputs found
Omori-like decay of postseismic velocities following continental earthquakes
Various mechanisms have been proposed to explain the transient, enhanced surface deformation rates following earthquakes. Unfortunately, these different mechanisms can produce very similar surface deformation patterns leading to difficulty in distinguishing between them. Here, we return to the observations themselves and compile near-field postseismic velocity measurements following moderate to large continental earthquakes. We find that these velocities have a remarkably consistent pattern, with velocity inversely proportional to time since the earthquake. This suggests that postseismic velocities show an Omori-like decay and that postseismic displacements increase logarithmically over time. These observations are inconsistent with simple, linear Maxwell or Burgers body viscoelastic relaxation mechanisms but are consistent with rate-and-state frictional afterslip models and power-law shear zone models. The results imply that postseismic surface deformation measurements are primarily the result of fault zone processes, and therefore, that the inference of lower crustal viscosities from near-field postseismic deformation requires care
Exosomes released by EBV-infected nasopharyngeal carcinoma cells convey the viral Latent Membrane Protein 1 and the immunomodulatory protein galectin 9
BACKGROUND: Nasopharyngeal carcinomas (NPC) are consistently associated with the Epstein-Barr virus (EBV). Their malignant epithelial cells contain the viral genome and express several antigenic viral proteins. However, the mechanisms of immune escape in NPCs are still poorly understood. EBV-transformed B-cells have been reported to release exosomes carrying the EBV-encoded latent membrane protein 1 (LMP1) which has T-cell inhibitory activity. Although this report suggested that NPC cells could also produce exosomes carrying immunosuppressive proteins, this hypothesis has remained so far untested. METHODS: Malignant epithelial cells derived from NPC xenografts – LMP1-positive (C15) or negative (C17) – were used to prepare conditioned culture medium. Various microparticles and vesicles released in the culture medium were collected and fractionated by differential centrifugation. Exosomes collected in the last centrifugation step were further purified by immunomagnetic capture on beads carrying antibody directed to HLA class II molecules. Purified exosomes were visualized by electron microscopy and analysed by western blotting. The T-cell inhibitory activities of recombinant LMP1 and galectin 9 were assessed on peripheral blood mononuclear cells activated by CD3/CD28 cross-linking. RESULTS: HLA-class II-positive exosomes purified from C15 and C17 cell supernatants were containing either LMP1 and galectin 9 (C15) or galectin 9 only (C17). Recombinant LMP1 induced a strong inhibition of T-cell proliferation (IC50 = 0.17 nM). In contrast recombinant galectin 9 had a weaker inhibitory effect (IC50 = 46 nM) with no synergy with LMP1. CONCLUSION: This study provides the proof of concept that NPC cells can release HLA class-II positive exosomes containing galectin 9 and/or LMP1. It confirms that the LMP1 molecule has intrinsic T-cell inhibitory activity. These findings will encourage investigations of tumor exosomes in the blood of NPC patients and assessment of their effects on various types of target cells
Epstein–Barr Virus DNase (BGLF5) induces genomic instability in human epithelial cells
Epstein–Barr Virus (EBV) DNase (BGLF5) is an alkaline nuclease and has been suggested to be important in the viral life cycle. However, its effect on host cells remains unknown. Serological and histopathological studies implied that EBV DNase seems to be correlated with carcinogenesis. Therefore, we investigate the effect of EBV DNase on epithelial cells. Here, we report that expression of EBV DNase induces increased formation of micronucleus, an indicator of genomic instability, in human epithelial cells. We also demonstrate, using γH2AX formation and comet assay, that EBV DNase induces DNA damage. Furthermore, using host cell reactivation assay, we find that EBV DNase expression repressed damaged DNA repair in various epithelial cells. Western blot and quantitative PCR analyses reveal that expression of repair-related genes is reduced significantly in cells expressing EBV DNase. Host shut-off mutants eliminate shut-off expression of repair genes and repress damaged DNA repair, suggesting that shut-off function of BGLF5 contributes to repression of DNA repair. In addition, EBV DNase caused chromosomal aberrations and increased the microsatellite instability (MSI) and frequency of genetic mutation in human epithelial cells. Together, we propose that EBV DNase induces genomic instability in epithelial cells, which may be through induction of DNA damage and also repression of DNA repair, subsequently increases MSI and genetic mutations, and may contribute consequently to the carcinogenesis of human epithelial cells
Contribution of the KSHV and EBV Lytic Cycles to Tumourigenesis
Kaposi’s Sarcoma-associated herpesvirus (KSHV) and Epstein Barr virus (EBV) are the causative agents of several malignancies. Like all herpesviruses, KSHV and EBV undergo distinct latent and lytic replication programmes. The transition between these states allows the establishment of a lifelong persistent infection, dissemination to sites of disease and the spread to new hosts. Latency-associated viral proteins have been well characterised in transformation and tumourigenesis pathways; however, a number of studies have shown that abrogation of KSHV and EBV lytic gene expression impairs the oncogenesis of several cancers. Furthermore, several lytically expressed proteins have been functionally tethered to the angioproliferative and anti-apoptotic phenotypes of virus-infected cells. As a result, the investigation and therapeutic targeting of KSHV and EBV lytic cycles may be essential for the treatment of their associated malignancies
Recherche automatique du reseau hydrographique a l'aide du modele numerique de terrain
SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc
Quasistatic response of loose cohesive granular materials
DEM-simulated model cohesive assemblies of spherical grains of diameter d, with contact tensile strength F0, once prepared in loose states, are quasistatically subjected to growing isotropic pressure P, and then to triaxial compression, maintaining lateral stresses σ2 = σ3 = P while increasing axial stress σ1 = P + q and strain є1. Reduced pressure P* = d2P/F0 varies from 0.1 (cohesion dominated case, for which systems typically equilibrate with solid fraction Ф ≃ 0.35), to large values for which the cohesionless behavior is retrieved. In triaxial compression, while the moderate strain response (є1 ~ 0.1) is influenced by initial coordination numbers and mesoscale heterogeneities, the approach to the critical state, as both q (deviator) and Ф steadily increase, gets slower for smaller P*. Critical ratio q/P strongly increases for decreasing P*, as roughly predicted in an “effective stress” scheme. Anomalously small elastic moduli are observed in the gel-like structures. While extensive geometric rearrangements take place, no shear banding is observed. Loose cohesive granular assemblies are thus capable of large quasistatic stable plastic strains and ductile rupture
Quasistatic response of loose cohesive granular materials
DEM-simulated model cohesive assemblies of spherical grains of diameter d, with contact tensile strength F0, once prepared in loose states, are quasistatically subjected to growing isotropic pressure P, and then to triaxial compression, maintaining lateral stresses σ2 = σ3 = P while increasing axial stress σ1 = P + q and strain є1. Reduced pressure P* = d2P/F0 varies from 0.1 (cohesion dominated case, for which systems typically equilibrate with solid fraction Ф ≃ 0.35), to large values for which the cohesionless behavior is retrieved. In triaxial compression, while the moderate strain response (є1 ~ 0.1) is influenced by initial coordination numbers and mesoscale heterogeneities, the approach to the critical state, as both q (deviator) and Ф steadily increase, gets slower for smaller P*. Critical ratio q/P strongly increases for decreasing P*, as roughly predicted in an “effective stress” scheme. Anomalously small elastic moduli are observed in the gel-like structures. While extensive geometric rearrangements take place, no shear banding is observed. Loose cohesive granular assemblies are thus capable of large quasistatic stable plastic strains and ductile rupture
Expression of the DNase encoded by the BGLF5 gene of Epstein-Barr virus in nasopharyngeal carcinoma epithelial cells.
In contrast with most Epstein-Barr virus (EBV)-infected healthy carriers, nasopharyngeal carcinoma patients frequently have increased serum levels of antibodies directed against EBV-DNase. These antibodies are potentially interesting serological markers for the diagnosis and the follow-up of nasopharyngeal carcinoma (NPC). In this context, it is important to determine whether malignant EBV-infected cells are the source of significant amounts of EBV-DNase contributing to antigenic stimulation. Therefore EBV-DNase expression has been investigated in several NPC specimens. A significant expression of this viral enzyme was demonstrated in both fresh biopsies and transplanted tumor lines. The DNase isolated from tumor has a molecular weight varying between 52 and 60 kDa and its activity eluted from a single-stranded DNA affinity column was specifically inhibited by both NPC sera and the rabbit polyclonal antibody against EBV-DNase. The enzyme activity was functional in the presence of 300 mM KCl, with which cellular DNases are completely inhibited. The DNase was mainly localized in epithelial tumor cells of both NPC biopsies and nude mice-derived NPC cells
Coseismic deformation of the May 21st, 2003, M w = 6.8 Boumerdes earthquake, Algeria, from GPS measurements
International audienceOn May 21st, 2003, a M w = 6.8 earthquake struck the central part of northern Algeria causing extensive damage in the Boumerdes area, 40 km east of Algiers. It is among the largest events to occur in the western Mediterranean over the past 25 years. We present GPS measurements of horizontal coseismic displacements that provide new constraints on the rupture geometry. Modeling the data with a uniform dislocation on a rectangular fault in an elastic half‐space, we find that the rupture occurred on a reverse fault dipping 42°S, with its upper edge 6 km offshore and lower edge 4 km inland. The amplitude distribution of the coseismic displacements indicates that the rupture did not reach the surface, at least in its western part, and ended to the west around 3.4°E. Offshore faults like that of the Boumerdes earthquake could account for part of the Africa‐Eurasia relative plate motion in the western Mediterranean and represent a significant seismic threat for Algeria