30 years of European Commission Radioactivity Environmental Monitoring data bank (REMdb) – an open door to boost environmental radioactivity research

The Radioactivity Environmental Monitoring data bank (REMdb) was created in the aftermath of the Chernobyl accident (1986) by the European Commission (EC) – Directorate-General Joint Research Centre (DG JRC), sited in Ispra (Italy). Since then it has been maintained there with the aim to keep a historical record of the Chernobyl accident and to store the radioactivity monitoring data gathered through the national environmental monitoring programs of the member states (MSs). The legal basis is the Euratom Treaty, Chapter III Health and Safety, Articles 35 and 36, which clarify that MSs shall periodically communicate to the EC information on environmental radioactivity levels. By collecting and validating this information in REMdb, JRC supports the DG for Energy in its responsibilities in returning qualified information to the MSs (competent authorities and general public) on the levels of radioactive contamination of the various compartments of the environment (air, water, soil) on the European Union scale. REMdb accepts data on radionuclide concentrations from EU MSs in both environmental samples and foodstuffs from 1984 onwards. To date, the total number of data records stored in REMdb exceeds 5 million, in this way providing the scientific community with a valuable archive of environmental radioactivity topics in Europe. Records stored in REMdb are publicly accessible until 2011 through an unrestricted repository “REM data bank – Years 1984–2006” https://doi.org/10.2905/jrc-10117-10024 (De Cort et al., 2007) and “REM data bank – Years 2007–2011” https://doi.org/10.2905/de42f259-fafe-4329-9798-9d8fabb98de5 (De Cort et al., 2012). Access to data from 2012 onwards is granted only after explicit request, until the corresponding monitoring report is published. Each data record contains information describing the sampling circumstances (sampling type, begin and end time), measurement conditions (value, nuclide, apparatus, etc.), location and date of sampling, and original data reference. In this paper the scope, features and extension of REMdb are described in detail.</p

5-Formylcytosine can be a stable DNA modification in mammals.

5-Formylcytosine (5fC) is a rare base found in mammalian DNA and thought to be involved in active DNA demethylation. Here, we show that developmental dynamics of 5fC levels in mouse DNA differ from those of 5-hydroxymethylcytosine (5hmC), and using stable isotope labeling in vivo, we show that 5fC can be a stable DNA modification. These results suggest that 5fC has functional roles in DNA that go beyond being a demethylation intermediate.This work was supported by the Cancer Research UK (C14303/A17197, S.B.), The Wellcome Trust (WT099232, S.B.; WT095645/Z/11/Z, W.R.) and the BBSRC (BB/K010867/1, W.R.).This is the accepted manuscript. It is currently embargoed pending publication

A role for caspase-8 and TRAIL-R2/DR5 in ER-stress induced apoptosis

Glab and colleagues examine in a recent paper apoptosis induced by some driverss of endoplasmic reticulum (ER) stress. They conclude that in contrast to a previously published report2 , DR5/TRAIL-R2 and caspase-8 are universally dispensable in ER stress-induced apoptosis. We argue here that their own data and other published reports indicate that in many models, DR5 and/or caspase-8 are essential players in apoptosis mediated by the unfolded protein response (UPR), upon chronic ER stress

Joint profiling of DNA methylation and chromatin architecture in single cells.

We report a molecular assay, Methyl-HiC, that can simultaneously capture the chromosome conformation and DNA methylome in a cell. Methyl-HiC reveals coordinated DNA methylation status between distal genomic segments that are in spatial proximity in the nucleus, and delineates heterogeneity of both the chromatin architecture and DNA methylome in a mixed population. It enables simultaneous characterization of cell-type-specific chromatin organization and epigenome in complex tissues

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

A screen for hydroxymethylcytosine and formylcytosine binding proteins suggests functions in transcription and chromatin regulation

MI is supported by the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme FP7/2007-2013/under REA grant agreement no. 290123 and was supported by Unipharma-Graduates 7 Da Vinci Programme. MJB is supported by a BBRSC studentship

Study on the uncertainty of passive area dosimetry systems for environmental radiation monitoring in the framework of the EMPIR "Preparedness" project

Abstract One of the objectives of the EMPIR project 16ENV04 "Preparedness" is the harmonization of methodologies for the measurement of doses with passive dosimetry systems for environmental radiation monitoring in the aftermath of a nuclear or radiological event. In such cases, measurements are often performed at low radiation dose rates, close to the detection limit of the passive systems. The parameters which may affect the dosimetric results of a passive dosimetry system are analyzed and four laboratories quantitatively evaluate the uncertainties of their passive dosimetry systems. Typical uncertainties of five dosimetric systems in four European countries are compared and the main sources of uncertainty are analyzed using the results of a questionnaire compiled for this specific purpose. To compute the characteristic limits of a passive dosimetry system according to standard ISO 11929, the study of the uncertainty of the system is the first step. In this work the uncertainty budget as well as the characteristic limits (decision thresholds and detection limits) are evaluated and the limitations and strengths of a complete analysis of all parameters are presented

Abrogation of Junctional Adhesion Molecule-A Expression Induces Cell Apoptosis and Reduces Breast Cancer Progression

Intercellular junctions promote homotypic cell to cell adhesion and transfer intracellular signals which control cell growth and apoptosis. Junctional adhesion molecule-A (JAM-A) is a transmembrane immunoglobulin located at tight junctions of normal epithelial cells of mammary ducts and glands. In the present paper we show that JAM-A acts as a survival factor for mammary carcinoma cells. JAM-A null mice expressing Polyoma Middle T under MMTV promoter develop significantly smaller mammary tumors than JAM-A positive mice. Angiogenesis and inflammatory or immune infiltrate were not statistically modified in absence of JAM-A but tumor cell apoptosis was significantly increased. Tumor cells isolated from JAM-A null mice or 4T1 cells incubated with JAM-A blocking antibodies showed reduced growth and increased apoptosis which paralleled altered junctional architecture and adhesive function. In a breast cancer clinical data set, tissue microarray data show that JAM-A expression correlates with poor prognosis. Gene expression analysis of mouse tumor samples showed a correlation between genes enriched in human G3 tumors and genes over expressed in JAM-A +/+ mammary tumors. Conversely, genes enriched in G1 human tumors correlate with genes overexpressed in JAM-A−/− tumors. We conclude that down regulation of JAM-A reduces tumor aggressive behavior by increasing cell susceptibility to apoptosis. JAM-A may be considered a negative prognostic factor and a potential therapeutic target

5-Hydroxymethylcytosine is a predominantly stable DNA modification.

5-Hydroxymethylcytosine (hmC) is an oxidation product of 5-methylcytosine which is present in the deoxyribonucleic acid (DNA) of most mammalian cells. Reduction of hmC levels in DNA is a hallmark of cancers. Elucidating the dynamics of this oxidation reaction and the lifetime of hmC in DNA is fundamental to understanding hmC function. Using stable isotope labelling of cytosine derivatives in the DNA of mammalian cells and ultrasensitive tandem liquid-chromatography mass spectrometry, we show that the majority of hmC is a stable modification, as opposed to a transient intermediate. In contrast with DNA methylation, which occurs immediately during replication, hmC forms slowly during the first 30 hours following DNA synthesis. Isotopic labelling of DNA in mouse tissues confirmed the stability of hmC in vivo and demonstrated a relationship between global levels of hmC and cell proliferation. These insights have important implications for understanding the states of chemically modified DNA bases in health and disease.We would like to acknowledge the CRUK CI Flow Cytometry and Histopathology/ISH core facilities for their contributions, David Oxley, Clive d’Santos and Donna Michelle-Smith for their support with mass spectrometry, Xiangang Zou for his help with mES cells and David Tannahill for critical reading of the manuscript. This work was funded by Cancer Research UK (all authors) and the Wellcome Trust Senior Investigator Award (S.B.).This is the accepted manuscript. The final version is available from Nature Chemistry at http://www.nature.com/nchem/journal/vaop/ncurrent/full/nchem.2064.html