Analyse des mutations des domaines ISDR et V3 de la protéine NS5A du virus de l'hépatite C avant le traitement par l'interféron avec ou sans ribavirine

Aim of the study. – The hepatitis C virus (HCV) non-structural NS5A protein has been controversially implicated in the resistance of HCV to interferon therapy in clinical studies. In Japan, mutations in the interferon sensitivity-determining region (ISDR) in the NS5A gene were associated with response to interferon therapy in patients infected with genotype 1b. In contrast, studies from Europe did not confirm such association. More recently, it has been suggested that the V3 domain outside the putative ISDR might also have amino acids changes that may be involved in the resistance to IFN. In this study, the relationship between NS5A mutations in ISDR and V3 domains and virological response to therapy were investigated. Materials and methods. – The NS5A gene was sequenced from 35 HCV genotype 1b infected patients at D0 of a prospective clinical trial of interferon therapy and interferon plus Ribavirin combination therapy. Results. – In the ISDR domain, we did not observe any significant differences in amino acids changes between responders (1.7 ± 1.8, n = 19, range 0–6) and non-responders (1.1 ± 0.8, n = 14, range: 0–3), (P = 0.483), to therapy before the beginning of treatment. In the V3 domain, we found more mutations in responders (6.5 ± 1.9, range: 2–11) than in non-responders (4.7 ± 1.2, range: 3–8) (P = 0.0013), before the beginning of treatment. Conclusion. – Our results confirm that, in Europe, the ISDR domain is not predictive for treatment success but suggest that the V3 domain have greater variability in responders than non-responders

Mutations within the hepatitis C virus genotype 1b E2-PePHD domain do not correlate with treatment outcome.

The hepatitis C virus (HCV) envelope protein 2 (E2) interacts in vitro with the interferon alpha (IFN-alpha)-inducible double-stranded RNA-activated protein kinase, suggesting a possible mechanism by which HCV may evade the antiviral effects of IFN-alpha. Variability in the part of the HCV E2 gene encoding the carboxy-terminal part of the protein, which includes the interaction domain (E2-PePHD), was explored in 25 patients infected with HCV genotype 1b and receiving IFN-alpha therapy. PCR products were generated and sequenced for 15 patients with a sustained response and for 10 patients with no virological response after treatment with IFN-alpha and ribavirin. PePHD amino acid sequences were obtained for isolates from serum collected before and during treatment, after 2 months in responders, and after 6 months in nonresponders. Quasispecies analysis of the pretreatment PePHD region was performed for isolates from patients displaying amino acid substitutions in this domain on direct sequencing. The E2-PePHD sequence was highly conserved in both resistant and susceptible genotype 1b strains and was identical to the prototype HCV type J sequence. No significant emergence of PePHD mutants during therapy was observed in our clonal analysis, and sporadic mutations and treatment outcomes were not found to be correlated. The PePHD sequence before or during treatment cannot be used to predict reliably the outcome of treatment in HCV type 1b-infected patients

Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy

AIM: To evaluate the implication of substitutions in the hepatitis C virus (HCV) non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported to interact with the HCV RNA-dependent RNA polymerase, NS5B, as well as with many cellular proteins, the function of NS5A in the life cycle of HCV remains unclear. METHODS: HCV quasispecies were studied by cloning and sequencing of sequential isolates from patients infected by HCV genotype 1b. Patients were treated by IFN-alpha2b for 3 mo followed by IFN-alpha2b alone or combined IFN-R therapy for 9 additional months. Patients were categorized into two groups based on their response to the treatments: 7 with sustained virological response (SVR) (quasispecies = 150) and 3 non-responders (NR) to IFN-R (quasispecies = 106). RESULTS: Prior to treatment, SVR patients displayed a lower complexity of quasispecies than NR patients. Most patients had a decrease in the complexity of quasispecies during therapy. Analysis of amino acids substitutions showed that the degree of the complexity of the interferon sensitivity-determining region (ISDR) and the V3 domain of NS5A protein was able to discriminate the two groups of patients. Moreover, SVR patients displayed more variability in the NS5A region than NR patients. CONCLUSION: These results suggest that detailed molecular analysis of the NS5A region may be important for understanding its function in IFN response during HCV 1b infection

Observation of the scaling dimension of fractional quantum Hall anyons

Unconventional quasiparticles emerging in the fractional quantum Hall regime present the challenge of observing their exotic properties unambiguously. Although the fractional charge of quasiparticles has been demonstrated since nearly three decades, the first convincing evidence of their anyonic quantum statistics has only recently been obtained and, so far, the so-called scaling dimension that determines the quasiparticles propagation dynamics remains elusive. In particular, while the non-linearity of the tunneling quasiparticle current should reveal their scaling dimension, the measurements fail to match theory, arguably because this observable is not robust to non-universal complications. Here we achieve an unambiguous measurement of the scaling dimension from the thermal to shot noise cross-over, and observe a long-awaited agreement with expectations. Measurements are fitted to the predicted finite temperature expression involving both the quasiparticles scaling dimension and their charge, in contrast to previous charge investigations focusing on the high bias shot noise regime. A systematic analysis, repeated on multiple constrictions and experimental conditions, consistently matches the theoretical scaling dimensions for the fractional quasiparticles emerging at filling factors 1/3, 2/5 and 2/3. This establishes a central property of fractional quantum Hall anyons, and demonstrates a powerful and complementary window into exotic quasiparticles

Le référentiel taxonomique Florical et les caractéristiques de la flore vasculaire indigène de la Nouvelle-Calédonie

The taxonomic reference base Florical and characteristics of the native vascular flora of New Caledonia. The floristic inventory presented here comprises the evolving computerised database Florical (http://www.botanique.nc/herbier/florical). As of the date of publication, it lists all native vascular plant species (as well as infraspecific taxa) present in the territory of New Caledonia, whether validly published or in press, along with their basionym, organised according to the most recent classifications systems (APG III 2009 for the angiosperms, Smith et at [2006] for the ferns and lycophytes, and Mabberley [2009] for the gymnosperms), accompanied by their status (native or endemic) and the various vegetation types in which they occur. After a brief historical review of our knowledge of New Caledonian botany, the characteristics (richness, composition and endemism) of the different taxonomic groups (ferns and lycophytes, gymnosperms and then angiosperms -mono- and dicotyledons) are analyzed, followed by an assessment of the distribution of these groups among the vegetation types. The vascular flora of New Caledonia is characterised by its high level of richness (3371 species, including 3099 for the flowering plants alone), despite the absence or under-representation of some taxa that are abundantly represented elsewhere in the tropics, and especially by its remarkable distinctiveness (with endemism at the species level reaching 74,7%, and 77.8% for the flowering plants). The flora stands out by the presence of several relictual taxa and a high level of speciation among certain groups, despite the fact that the island was re-colonised relatively recently following the total submersion of its much older basement during the Paleocene and the Oligocene. Details of the measures taken to conserve this extraordinary natural heritage show that only 3.4% of the territory's total surface area is effectively protected. Despite the undeniable progress made in recent years by the authorities concerned, significant work remains to be done, especially in the northern Province

Concerted changes in tropical forest structure and dynamics: evidence from 50 South American long-term plots

Several widespread changes in the ecology of old-growth tropical forests have recently been documented for the late twentieth century, in particular an increase in stem turnover (pan-tropical), and an increase in above-ground biomass (neotropical). Whether these changes are synchronous and whether changes in growth are also occurring is not known. We analysed stand-level changes within 50 long-term. monitoring plots from across South America spanning 1971-2002. We show that: (i) basal area (BA: sum of the cross-sectional areas of all trees in a plot) increased significantly over time (by 0.10 +/- 0.04 m(2) ha(-1) yr(-1), mean +/- 95% CI); as did both (ii) stand-level BA growth rates (sum of the increments of BA of surviving trees and BA of new trees that recruited into a plot); and (iii) stand-level BA mortality rates (sum of the cross-sectional areas of all trees that died in a plot). Similar patterns were observed on a per-stem basis: (i) stem density (number of stems per hectare; 1 hectare is 10(4) m(2)) increased significantly over time (0.94 +/- 0.63 stems ha(-1) yr(-1)); as did both (ii) stem recruitment rates; and (iii) stem mortality rates. In relative terms, the pools of BA and stem density increased by 0.38 +/- 0.15% and 0.18 +/- 0.12% yr(-1), respectively. The fluxes into and out of these pools-stand-level BA growth, stand-level BA mortality, stem recruitment and stem mortality rates-increased, in relative terms, by an order of magnitude more. The gain terms (BA growth, stem recruitment) consistently exceeded the loss terms (BA loss, stem mortality) throughout the period, suggesting that whatever process is driving these changes was already acting before the plot network was established. Large long-term increases in stand-level BA growth and simultaneous increases in stand BA and stem density imply a continent-wide increase in resource availability which is increasing net primary productivity and altering forest dynamics. Continent-wide changes in incoming solar radiation, and increases in atmospheric concentrations of CO2 and air temperatures may have increased resource supply over recent decades, thus causing accelerated growth and increased dynamism across the world's largest tract of tropical forest

Pattern and process in Amazon tree turnover, 1976-2001

Previous work has shown that tree turnover, tree biomass and large liana densities have increased in mature tropical forest plots in the late twentieth century. These results point to a concerted shift in forest ecological processes that may already be having significant impacts on terrestrial carbon stocks, fluxes and biodiversity. However, the findings have proved controversial, partly because a rather limited number of permanent plots have been monitored for rather short periods. The aim of this paper is to characterize regional-scale patterns of 'tree turnover' (the rate with which trees die and recruit into a population) by using improved datasets now available for Amazonia that span the past 25 years. Specifically, we assess whether concerted changes in turnover are occurring, and if so whether they are general throughout the Amazon or restricted to one region or environmental zone. In addition, we ask whether they are driven by changes in recruitment, mortality or both. We find that: (i) trees 10 cm or more in diameter recruit and die twice as fast on the richer soils of southern and western Amazonia than on the poorer soils of eastern and central Amazonia; (ii) turnover rates have increased throughout Amazonia over the past two decades; (iii) mortality and recruitment rates have both increased significantly in every region and environmental zone, with the exception of mortality in eastern Amazonia; (iv) recruitment rates have consistently exceeded mortality rates; (v) absolute increases in recruitment and mortality rates are greatest in western Amazonian sites; and (vi) mortality appears to be lagging recruitment at regional scales. These spatial patterns and temporal trends are not caused by obvious artefacts in the data or the analyses. The trends cannot be directly driven by a mortality driver (such as increased drought or fragmentation-related death) because the biomass in these forests has simultaneously increased. Our findings therefore indicate that long-acting and widespread environmental changes are stimulating the growth and productivity of Amazon forests

Labyrinthine window rupture as a cause of acute sensorineural hearing loss

Labyrinthine window rupture (LWR) is one cause of acute sensorineural hearing loss and need for early exploration is clear for good improved hearing. Acute sensorineural hearing loss of 60 dB or more treated from May 2006 to May 2010 were retrospectively analyzed. There were 21 ears of severe deafness, 18 ears of profound deafness, and 10 ears of total deafness. All patients were examined with temporal bone CT. Space-occupying lesions around the labyrinthine windows were suggestive images of LWR. Thirty-five ears were operated for LWR while 14 ears of SHL received conservative treatments. Fifty-seven percent of LWR improved 30 dB or more after sealing of both labyrinthine windows. Of the 15 markedly recovered ears, 14 ears were operated within 2 weeks from the onset. Of the five cured ears, four ears were operated within a week from the onset. As for the hearing prognosis of SHL, 88% of severe and profound deafness improved 30 dB or more but total deafness did not improve more than 30 dB. Exclusion of LWR from SHL and early surgical intervention in LWR will bring about good hearing prognosis to both LWR and SHL