Relationship between humoral response against hepatitis C virus and disease overcome

International audienceConclusionHumoral response against hepatitis C virus linear epitopes is partly modified according to the disease state. This study highlights the importance of considering relative quantities of antibodies with different specificities rather than the amount of each antibody.Hepatitis C virus infection leads to liver disease whose severity can range from mild to serious lifelong illness. However the parameters involved in the evolution of the disease are still unknown. Among other factors, the virus-elicited antibody profile is suspected to play a role in the outcome of the disease. Analysis of the relationship between anti-virus antibodies and disease state requires the analysis of a large number of serums from patients (hepatitis C virus+) and of epitopes from the viral proteins. Such a study would benefit from microarray-based screening systems that are appropriate for high-throughput assays.We used a method combining peptide chips and surface plasmon resonance imaging previously shown to be suitable for analyzing complex mediums and detecting peptide-protein interactions. 56 peptides covering the entire viral proteome were grafted on chips and their interaction with antibodies present in the 68 injected serums from infected and non-infected donors was measured. Statistical analyses were conducted to determine a possible relationship between antibodies (specificity and amount) and disease states.A good discrimination between infected and non-infected donors validated our approach, and several correlations between antibodies profiles and clinical parameters have been identified. In particular, we demonstrated that ratios between particular antibodies levels allow for accurate discrimination of patients according to their pathologic states

A new role for complement C3: regulation of antigen processing through an inhibitory activity.

International audienceIncreasing evidence underlines the involvement of complement component C3 in the establishment of acquired immunity which appears to play a complex role and to act at different levels. As antigen proteolysis by antigen presenting cells is a key event in the control of antigen presentation efficiency, and consequently in the quality of the immune response, we investigated whether C3 could modulate this step. Our results demonstrate for the first time that C3 can interfere with antigen proteolysis: (i) proteolysis of tetanus toxin (TT) by the lysosomal fraction from a human monocytic cell line (U937) is impaired in the presence of C3, (ii) this effect is C3-specific and involves the C3c fragment of the protein, (iii) C3c is effective even after disulfide disruption, but none of its three constitutive peptides is individually accountable for this inhibitory effect and (iv) the target-protease(s) exhibit(s) a serine-protease activity. The physiological relevance of our results is demonstrated by experiments showing a subcellular colocalisation of TT and C3 after their uptake by U937 and the reduction of TT proteolysis once internalised together with C3. These results highlight a novel role for C3 that broadens its capacity to modulate acquired immune response

Enhanced susceptibility of T lymphocytes to oxidative stress in the absence of the cellular prion protein.: PrPC and oxidative stress in T lymphocytes

International audienceThe cellular prion glycoprotein (PrP(C)) is ubiquitously expressed but its physiologic functions remain enigmatic, particularly in the immune system. Here, we demonstrate in vitro and in vivo that PrP(C) is involved in T lymphocytes response to oxidative stress. By monitoring the intracellular level of reduced glutathione, we show that PrP(-/-) thymocytes display a higher susceptibility to H(2)O(2) exposure than PrP(+/+) cells. Furthermore, we find that in mice fed with a restricted diet, a regimen known to increase the intracellular level of ROS, PrP(-/-) thymocytes are more sensitive to oxidative stress. PrP(C) function appears to be specific for oxidative stress, since no significant differences are observed between PrP(-/-) and PrP(+/+) mice exposed to other kinds of stress. We also show a marked evolution of the redox status of T cells throughout differentiation in the thymus. Taken together, our results clearly ascribe to PrP(C) a protective function in thymocytes against oxidative stress

Acceleration and collimation of relativistic MHD disk winds

We perform axisymmetric relativistic magnetohydrodynamic (MHD) simulations to investigate the acceleration and collimation of jets and outflows from disks around compact objects. The fiducial disk surface (respectively a slow disk wind) is prescribed as boundary condition for the outflow. We apply this technique for the first time in the context of relativistic jets. The strength of this approach is that it allows us to run a parameter study in order to investigate how the accretion disk conditions govern the outflow formation. Our simulations using the PLUTO code run for 500 inner disk rotations and on a physical grid size of 100x200 inner disk radii. In general, we obtain collimated beams of mildly relativistic speed and mass-weighted half-opening angles of 3-7 degrees. When we increase the outflow Poynting flux by injecting an additional disk toroidal field into the inlet, Lorentz factors up to 6 are reached. These flows gain super-magnetosonic speed and remain Poynting flux dominated. The light surface of the outflow magnetosphere tends to align vertically - implying three relativistically distinct regimes in the flow - an inner sub-relativistic domain close to the jet axis, a (rather narrow) relativistic jet and a surrounding subrelativistic outflow launched from the outer disk surface - similar to the spine-sheath structure currently discussed for asymptotic jet propagation and stability. The outer subrelativistic disk wind is a promising candidate for the X-ray absorption winds that are observed in many radio-quiet AGN.Comment: 22 pages, 15 figures; accepted for publication in ApJ; incorporates changes according to refere

HIV-1 VPR impairs cell growth through the inactivation of two genetically distinct host cell proteins

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The envelope of human endogenous retrovirus in neuro-inflammation

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Sr/Ca ratios and oxygen isotopes from sclerosponges: Temperature history of the Carribean mixed layer and thermocline during the Little Ice Age

We investigate aragonitic skeletons of the Caribbean sclerosponge Ceratoporella nicholsoni from Jamaica, 20 m below sea level (mbsl), and Pedro Bank, 125 mbsl. We use d18O and Sr/Ca ratios as temperature proxies to reconstruct the Caribbean mixed layer and thermocline temperature history since 1400 A.D. with a decadal time resolution. Our age models are based on U/Th dating and locating of the radiocarbon bomb spike. The modern temperature difference between the two sites is used to tentatively calibrate the C. nicholsoni Sr/Ca thermometer. The resulting calibration points to a temperature sensitivity of Sr/Ca in C. nicholsoni aragonite of about -0.1 mmol/mol/K. Our Sr/Ca records reveal a pronounced warming from the early 19th to the late 20th century, both at 20 and 125 mbsl. Two temperature minima in the shallow water record during the late 17th and early 19th century correspond to the Maunder and Dalton sunspot minima, respectively. Another major cooling occurred in the late 16th century and is not correlatable with a sunspot minimum. The temperature contrast between the two sites decreased from the 14th century to a minimum in the late 17th century and subsequently increased to modern values in the early 19th century. This is interpreted as a long-term deepening and subsequent shoaling of the Caribbean thermocline. The major trends of the Sr/Ca records are reproduced in both specimens but hardly reflected in the d18O records

Strontium isotope fractionation of planktic foraminifera and inorganic calcite

We have investigated the strontium isotope fractionation (Δ88/86Srcarb–aq) between inorganic calcite and aqueous Sr2+ ions by precipitation experiments at a constant temperature of 25 °C and precipitation rates (R) ranging from 102.3 to 104.2 μmol/m2/h. Strontium isotope ratios were measured using the 87Sr–84Sr double spike technique. It was found that strontium isotope fractionation in these calcites is strongly dependent on the precipitation rate: View the MathML source The measured δ88/86Sr values are significantly correlated with previously measured δ44/40Ca and Sr/Ca values of the same calcite samples: Δ88/86Srcarb–aq=+0.18∗Δ44/40Cacarb–aq-0.01 View the MathML source The slope of 88Sr/86Sr versus 44Ca/40Ca fractionation is 0.18 ± 0.04 and compatible with a kinetic fractionation during dehydration of the strontium and calcium ions, but not with isotope fractionation in a diffusive boundary layer. Using published equilibrium Δ44/40Cacarb–aq and View the MathML source values we estimate the equilibrium isotope fractionation of strontium to be very close to zero (Δ88/86Sreq(carb–aq) = −0.01 ± 0.06‰). This estimate is confirmed by strontium isotope values of natural inorganic calcites that precipitated very slowly in basalts of the ocean crust. The results from the inorganic calcites are used to explain strontium isotope fractionation of planktic foraminifera. Specimens of two warm water species (Globigerinoides ruber and Globigerinoides sacculifer) were picked from the Holocene section of a Caribbean sediment core. We found no significant difference in δ88/86Sr between the two species. In addition, G. ruber specimens from Marine Isotope Stage 2 in the same core show δ88/86Sr values identical to the Holocene specimens. The strontium isotopes of both foraminifera species are strongly fractionated (Δ88/86Srcarb–aq = −0.248 ± 0.005‰) when compared to published data of other major marine calcifiers. Applying the results from the inorganic precipitation experiments we find that the strong foraminiferal strontium isotope fractionation can be explained by calcification in a largely open system at high precipitation rates, comparable in magnitude to rates known from scleractinian reef corals. This interpretation is in good agreement with the kinetic calcification model for planktic foraminifera by Kisakürek et al. (2011), which was based on calcium isotopes and elemental Sr/Ca ratios

Monitoring of French Polynesia coral reefs and their recent development

French Polynesia, consisting of 118 islands in the centre of the Pacific Ocean, has more than 15000 km2 of reefs and lagoons managed by the local government. Tourism and pearl culture are the two main economic resources of the country. Polynesian coral reefs are extremely diverse and are among those for which we have thorough knowledge. The exploitation of local resources has been recorded for multiple decades and includes : coral materials, fishing, harvest and export of mother-of-pearl molluscs, pearl production, and ornamental fish. All over the country, many monitoring programmes have been launched to measure the health of reefs and the natural and anthropogenic perturbations that they suffer : hurricanes and seismic events, water quality, health of benthic and fish communities, pearl oyster pathology and radiobiology. These data, collected over the last few decades, allowed to defi ne the relative importance of natural and anthropogenic degradation on reefs and lagoons, and to explain the present status of reefs at different spatial scales. Devastating hurricanes are rare (1903-1906, 1982-1983 and occasionally at other times), but they may annihilate outer slope coral communities on some islands. Bleaching events with considerable coral mortality at different geographical scales occurred mainly in 1991, 1994 and 2003. Outbreaks of Acanthaster destroyed numerous reefs (lagoons and outer slopes) from 1978-1982 and a new demographic wave began in 2006 at many Society islands. Eutrophication events only occurred occasionally and only in some lagoons. Whereas natural catastrophic events degrade the coral reef ecosystem across many islands, at the archipelago or even regional scale, anthropogenic degradation is limited to a few Society Islands, occurring rarely on atolls and not at all on those (one third) which are uninhabited. The main causes of reef degradation in some areas of Tahiti and Moorea include the embankment of fringing zones, coral mining, overfishing, absence of urban sewage treatment and the development of leisure and tourism activities. Because of its large geographical extent, one may conclude that major reef degradation in French Polynesia is caused by catastrophic natural events. On the other hand, anthropogenic degradation is more localized. Unfortunately, the synergistic effects of these causes of degradation prevent reefs from recovering. Optimum coral cover on French Polynesian outer reef slopes is between 50-60 %. After a major destructive impact (hurricane, bleaching, Acanthaster) a reef is reduced to less than 10 % coral cover, however if no more major disturbance events occur a reef will recover in about 12 years. Most of the 15000 km2 of reefs and lagoons in French Polynesia are in good health, and along with their neighbouring reefs in East and Central Pacific they are considered as the least degraded reefs worldwide and at a low risk of becoming degraded in the few next decades. However, we are more and more anxious about the future of reefs in the world particularly because present simulations predict that major impacts of climate change would include : elevation of sea surface temperatures, increase in the strength of hurricanes and acidification of seawater which will affect the formation of coral structuresLa Polynésie française, 118 îles au coeur du Pacifique, possède une surface de plus de 15000 km2 de récifs et lagons gérés par le gouvernement polynésien. Le tourisme et la perliculture représentent les deux ressources économiques majeures du Pays. Les formations récifales très diversifiées sont parmi les mieux connues. Plusieurs suivis d'exploitation des ressources sont opérationnels depuis des décennies : granulats coralliens, pêche pour l'alimentation, collecte et exportation de mollusques nacriers, production de perles, poissons d'ornement. À l'échelle du Pays de très nombreux programmes de surveillance de l'état des récifs et des perturbations qu'ils subissent, naturelles et anthropiques, ont été mis en place: perturbations cycloniques et sismiques, qualité des eaux, état de santé des peuplements benthiques et ichtyologiques, pathologie des nacres, radiobiologie. Toutes ces données recueillies au fil des décennies ont permis d'établir l'importance relative des dégradations naturelles et anthropiques sur les récifs et lagons polynésiens et d'expliquer leur état de santé actuel en considérant différentes échelles spatiales. Les périodes cycloniques dévastatrices pour les récifs sont rares (1903-1906, 1982-1983 et épisodiquement) mais les cyclones ont parfois anéanti les communautés coralliennes de pentes externes dans certaines îles. Les blanchissements suivis de mortalités importantes à des échelles spatiales diverses, ont été surtout ceux de 1991, 1994 et 2003. Les explosions démographiques d'Acanthaster ont détruit de nombreux récifs (lagons et pentes externes) en 1978-1982 et une nouvelle pullulation s'amplifie depuis 2006 dans plusieurs îles de la Société. Les crises dystrophiques n'ont perturbé qu'épisodiquement certains lagons. Si les événements naturels précédents dégradent les récifs à l'échelle de plusieurs îles, d'archipel ou du Pays, les dégradations anthropiques sont limitées à quelques îles peuplées de la Société, plus exceptionnellement dans les atolls et encore moins dans un tiers d'entre eux qui sont inhabités. Les remblais en zone frangeante, les extractions de matériaux coralliens, la surpêche, l'absence de réseaux d'assainissement des eaux usées urbaines et le développement d'activités de loisir et du tourisme sont les causes essentielles de la dégradation des communautés coralliennes du lagon dans certains secteurs de Tahiti et de Moorea. Ainsi apparaît-il clairement que les dégradations majeures des récifs en Polynésie sont occasionnées par des phénomènes naturels compte tenu de leur étendue géographique. En revanche les dégradations anthropiques sont géographiquement plus localisées. Malheureusement la synergie des deux causes de dégradation ne facilite pas la récupération des récifs. Il est établi qu'une pente externe avec un recouvrement corallien de 50-60 % est à son optimum. Une dégradation majeure (cyclone, blanchissement, Acanthaster) réduit ce recouvrement à moins de 10 %. La communauté met une douzaine d'années pour revenir au recouvrement optimum si aucune autre perturbation importante ne survient. La très large majorité des 15000 km2 de récifs et lagons de Polynésie française sont en bonne santé. Avec leurs voisins du Pacifique Est et Central, ces formations coralliennes sont considérées comme les moins dégradées au monde et à faible risque de dégradation dans les prochaines décennies