Medulloblastoma and ependymoma cells display levels of 5-carboxylcytosine and elevated TET1 expression

Background Alteration of DNA methylation (5-methylcytosine, 5mC) patterns represents one of the causes of tumorigenesis and cancer progression. Tet proteins can oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine (5caC). Although the roles of these oxidised forms of 5mC (oxi-mCs) in cancer pathogenesis are still largely unknown, there are indications that they may be involved in the mechanisms of malignant transformation. Thus, reduction of 5hmC content represents an epigenetic hallmark of human tumours and, according to our recent report; 5caC is enriched in a proportion of breast cancers and gliomas. Nevertheless, the distribution of oxi-mCs in paediatric brain tumours has not been assessed. Findings Here we analyse the global levels and spatial distribution of 5hmC and 5caC in 4 brain tumour cell lines derived from paediatric sonic hedgehog (SHH) pathway activated medulloblastomas (Daoy and UW228-3) and ependymomas (BXD-1425EPN and DKFZEP1NS). We show that, unlike HeLa cells, the paediatric tumour cell lines possess both 5hmC and 5caC at immunochemically detectable levels, and demonstrate that both modifications display high degrees of spatial overlap in the nuclei of medulloblastomas and ependymomas. Moreover, although 5hmC levels are comparable in the 4 brain tumour cell lines, 5caC staining intensities differ dramatically between them with highest levels of this mark in a subpopulation of DKFZ-EP1NS cells. Remarkably, the 5caC enrichment does not correlate with 5hmC levels and is not associated with alterations in Thymine DNA Glycosylase (TDG) expression in SHH medulloblastoma and ependymoma cell lines, but corresponds to elevated levels of TET1 transcript in UW228-3 and DKFZ-EP1NS cells. Conclusions We demonstrate that both 5caC enrichment and elevated TET1 expression are observed in SHH medulloblastomas and ependymomas. Our results suggest that increased Tet-dependent 5mC oxidation may represent one of the epigenetic signatures of cancers with neural stem cell origin and, thus, may contribute to development of novel approaches for diagnosis and therapy of the brain tumours

Genome-Wide Identification of Molecular Pathways and Biomarkers in Response to Arsenic Exposure in Zebrafish Liver

10.1371/journal.pone.0068737PLoS ONE87-POLN

Carbon Dioxide Utilisation -The Formate Route

UIDB/50006/2020 CEEC-Individual 2017 Program Contract.The relentless rise of atmospheric CO2 is causing large and unpredictable impacts on the Earth climate, due to the CO2 significant greenhouse effect, besides being responsible for the ocean acidification, with consequent huge impacts in our daily lives and in all forms of life. To stop spiral of destruction, we must actively reduce the CO2 emissions and develop new and more efficient “CO2 sinks”. We should be focused on the opportunities provided by exploiting this novel and huge carbon feedstock to produce de novo fuels and added-value compounds. The conversion of CO2 into formate offers key advantages for carbon recycling, and formate dehydrogenase (FDH) enzymes are at the centre of intense research, due to the “green” advantages the bioconversion can offer, namely substrate and product selectivity and specificity, in reactions run at ambient temperature and pressure and neutral pH. In this chapter, we describe the remarkable recent progress towards efficient and selective FDH-catalysed CO2 reduction to formate. We focus on the enzymes, discussing their structure and mechanism of action. Selected promising studies and successful proof of concepts of FDH-dependent CO2 reduction to formate and beyond are discussed, to highlight the power of FDHs and the challenges this CO2 bioconversion still faces.publishersversionpublishe

Interaction of two imidazolium gemini surfactants with two model proteins BSA and HEWL

Gemini surfactants and their interactions with proteins have gained considerable scientific interest, especially when amyloidogenic proteins are taken into account. In this work, the influence of two selected dicationic (gemini) surfactants (3,3′-[1,8-(2,7-dioxaoctane)]bis(1-dodecylimidazolium) chloride and 3,3′-[1,12-(2,11-dioxadodecane)]bis(1-dodecylimidazolium) chloride) on two model proteins, bovine serum albumin (BSA) and hen egg white lysozyme (HEWL), have been investigated. A pronounced and sophisticated influence on BSA structure has been revealed, including a considerable change of protein radius of gyration as well as substantial alteration of its secondary structure. Radius of gyration has been found to rise significantly with addition of surfactants and to fall down for high surfactants concentration. Similarly, a remarkable fall of secondary structure (α-helix content) has been observed, followed by its partial retrieval for high surfactants concentration. A strong aggregation of BSA has been observed for a confined range of surfactants concentrations as well. In case of HEWL-gemini system, on the other hand, the protein-surfactant interaction was found to be weak. Molecular mechanisms explaining such behaviour of protein-surfactant systems have been proposed. The differences of properties of both studied surfactants have also been discussed

Forced Vibration Analysis in the Context of Dynamic SIFs in Impact Bending Tests

Motion of a Timoshenko beam with a crack is analyzed by representing it through a massless rotational spring. This is relevant for evaluation of dynamic stress intensity factor (DSIF) in one- or three-point impact bend tests. The model predictions compare well with experimental results reported in the literature