Cryonotothenioidea is the main group of fishes that thrive in the extremely cold Antarctic environment, thanks to the acquisition of peculiar morphological, physiological and molecular adaptations. We have previously disclosed that IgM, the main immunoglobulin isotype in teleosts, display typical cold-adapted features. Recently, we have analyzed the gene encoding the heavy chain constant region (CH) of the IgT isotype from the Antarctic teleost Trematomus bernacchii (family Nototheniidae), characterized by the near-complete deletion of the CH2 domain. Here, we aimed to track the loss of the CH2 domain along notothenioid phylogeny and to identify its ancestral origins. To this end, we obtained the IgT gene sequences from several species belonging to the Antarctic families Nototheniidae, Bathydraconidae and Artedidraconidae. All species display a CH2 remnant of variable size, encoded by a short Cτ2 exon, which retains functional splicing sites and therefore is included in the mature transcript. We also considered representative species from the three non-Antarctic families: Eleginopsioidea (Eleginops maclovinus), Pseudaphritioidea (Pseudaphritis urvillii) and Bovichtidae (Bovichtus diacanthus and Cottoperca gobio). Even though only E. maclovinus, the sister taxa of Cryonotothenioidea, shared the partial loss of Cτ2, the other non-Antarctic notothenioid species displayed early molecular signatures of this event. These results shed light on the evolutionary path that underlies the origins of this remarkable gene structural modification.

Cell identity is determined by chromatin structure and the profiles of gene expression, which are dependent on chromatin accessibility and DNA methylation of regions critical for gene expression, such as enhancers and promoters. These epigenetic modifications are required for mammalian development and are essential for the establishment and the maintenance of the cellular identity. DNA methylation was once thought to be a permanent repressive epigenetic mark, but systematic analysis in various genomic contexts reveals a more dynamic regulation than previously thought. In fact, both active DNA methylation and demethylation occur during cell fate commitment and terminal differentiation. To link methylation signatures of specific genes to their expression profiles, we have determined the methyl-CpG configurations of the promoters of five genes switched on and off during murine postnatal brain differentiation by bisulfite-targeted sequencing. We report here the structure of significant, dynamic and stable methyl-CpG profiles associated with silencing or activation of expression of genes during neural stem cell and brain postnatal differentiation. Strikingly, these methylation cores mark different mouse brain areas and cell types derived from the same areas during differentiation.

The rapid introduction of DAAs has revolutionized the treatment of chronic HCV infection, however some concerns have been arose about their early and long term safety in real life settings. Therefore, these drugs achieve a robust and sustained virological response in a short duration of treatment, being a quick winning option, but, what then? At now an extensive follow-up in real life settings does not exist particularly on HCC occurrence as recently suggested in a Cochrane review . In this regard from February 2015 to December 2017 a group of 5 Hospital and Academic Centers in Southern Italy (Campania Region) managed an observational, prospective, real-life study on efficacy and safety of DAAs treatment schedule enrolling 1022 consecutive HCV patients treated with IFN-free DAAs regimens being followed-up for 24 months. Our preliminary data on the first 360 patients out of 1022 whose completed at least 66 weeks follow-up, based on clinical, laboratory and expert ultrasonography every three months, showed an SVR in 342 out 360 (95%) patients of which 9 had a new diagnosed HCC (2.63%). Specifically HCC developed in mean after 16,2 months after end of treatment as one or more nodules (2-3 cm in mean) with an increase in alpha-fetoprotein 10 x u.n.v (n.v. <15 UI/mL) in patients with F4 fibrosis staging at the time of treatment enrolment. In conclusion, in view of our findings and literature evidences, regular clinical, laboratory and expert ultrasonography follow-up should carefully performed also on these patients and the current Faster, Higher, Stronger approach to the new antivirals development should strongly be revisited in the light of possible late adverse events like HCC occurrence and the relative economic impact on health care system cost.