Recent evidence of underestimated circulation of hepatitis C virus intergenotypic recombinant strain RF2k/1b in the Rhône-Alpes region, France, January to August 2014: implications for antiviral treatment.

International audienceSince the beginning of 2014, hepatitis C virus (HCV) recombinant forms RF2k/1b have been detected in the Rhône-Alpes French region in 10 patients originating from the Caucasus area. Circulation of this particular HCV strain is very likely to be underestimated. It is also prone to be misgenotyped when using genotyping methods based on the 5' region of the viral genome, which may lead to suboptimal treatment

First NGS full genome characterization of a hepatitis C virus genotype 7 divergent subtype.

We report the near full length genome sequence, of an hepatitis C virus isolate from a man originating from Democratic Republic of Congo, whose genotype could not be determined by the routinely used sequence technique.The near-complete genome sequence of this variant BAK1 was obtained by the association of two next generation sequencing technologies.Evolutionary analysis indicates that this isolate BAK1 could be the first reported strain belonging to a new HCV-7b subtype. This new subtype has been incorrectly identified as genotype 2 by Versant HCV Genotype 2.0 assay (LiPA).The requirement of three independent isolates has been filled and a new subtype can be assigned. More examples of HCV-7 are required to better understand its origin, its pathogenicity and its relationship with genotype 2

First next-generation sequencing full-genome characterization of a hepatitis C virus genotype 7 divergent subtype

International audienc

First NGS full genome characterization of a hepatitis C virus genotype 7 divergent subtype.

We report the near full length genome sequence, of an hepatitis C virus isolate from a man originating from Democratic Republic of Congo, whose genotype could not be determined by the routinely used sequence technique.The near-complete genome sequence of this variant BAK1 was obtained by the association of two next generation sequencing technologies.Evolutionary analysis indicates that this isolate BAK1 could be the first reported strain belonging to a new HCV-7b subtype. This new subtype has been incorrectly identified as genotype 2 by Versant HCV Genotype 2.0 assay (LiPA).The requirement of three independent isolates has been filled and a new subtype can be assigned. More examples of HCV-7 are required to better understand its origin, its pathogenicity and its relationship with genotype 2

Notch signaling is significantly suppressed in basal cell carcinomas and activation induces basal cell carcinoma cell apoptosis

A subset of basal cell carcinomas (BCCs) are directly derived from hair follicles (HFs). In some respects, HFs can be defined as ‘ordered’ skin appendage growths, while BCCs can be regarded as ‘disordered’ skin appendage growths. The aim of the present study was to examine HFs and BCCs to define the expression of common and unique signaling pathways in each skin appendage. Human nodular BCCs, along with HFs and non-follicular skin epithelium from normal individuals, were examined using microarrays, qPCR, and immunohistochemistry. Subsequently, BCC cells and root sheath keratinocyte cells from HFs were cultured and treated with Notch signaling peptide Jagged1 (JAG1). Gene expression, protein levels, and cell apoptosis susceptibility were assessed using qPCR, immunoblotting, and flow cytometry, respectively. Specific molecular mechanisms were found to be involved in the process of cell self-renewal in the HFs and BCCs, including Notch and Hedgehog signaling pathways. However, several key Notch signaling factors showed significant differential expression in BCCs compared with HFs. Stimulating Notch signaling with JAG1 induced apoptosis of BCC cells by increasing Fas ligand expression and downstream caspase-8 activation. The present study showed that Notch signaling pathway activity is suppressed in BCCs, and is highly expressed in HFs. Elements of the Notch pathway could, therefore, represent targets for the treatment of BCCs and potentially in hair follicle engineering

Functional Interaction of Aurora-A and PP2A during Mitosis

Entry into mitosis is a highly regulated process, promoted by the activated Cyclin B1/Cdk1 complex. Activation of this complex is controlled, in part, by the protein kinase Aurora-A, which is a member of a multigenic serine/threonine kinase family. In normal cells, Aurora-A activity is regulated, at least in part, by degradation through the APC-ubiquitin-proteasome pathway. It has recently been proposed that, in Xenopus, Aurora-A degradation can be inhibited by phosphorylation. It would thus be expected that a phosphatase activity would release this blockade at the end of mitosis. Here, we have shown that the protein phosphatase PP2A and Aurora-A are colocalized at the cell poles during mitosis in human cells and interact within the same complex. Using the PP2A inhibitor okadaic acid and an RNAi approach, we have shown that this interaction is functional within the cell. PP2A/Aurora-A interaction is promoted by an S51D mutation in Aurora-A and inhibited by a phosphomimetic peptide centered around Aurora-A S51, thereby strongly suggesting that PP2A controls Aurora-A degradation by dephosphorylating serine 51 in the A box of the human enzyme

Members of the miRNA-200 Family Regulate Olfactory Neurogenesis

MicroRNAs (miRNAs) are highly expressed in vertebrate neural tissues, but the contribution of specific miRNAs to the development and function of different neuronal populations is still largely unknown. We report that miRNAs are required for terminal differentiation of olfactory precursors in both mouse and zebrafish but are dispensable for proper function of mature olfactory neurons. The repertoire of miRNAs expressed in olfactory tissues contains over 100 distinct miRNAs. A subset, including the miR-200 family, shows high olfactory enrichment and expression patterns consistent with a role during olfactory neurogenesis. Loss of function of the miR-200 family phenocopies the terminal differentiation defect observed in absence of all miRNA activity in olfactory progenitors. Our data support the notion that vertebrate tissue differentiation is controlled by conserved subsets of organ-specific miRNAs in both mouse and zebrafish and provide insights into control mechanisms underlying olfactory differentiation in vertebrates