Ficus racemosa Stem Bark Extract: A Potent Antioxidant and a Probable Natural Radioprotector

Ethanol extract (FRE) and water extract (FRW) of Ficus racemosa (family: Moraceae) were subjected to free radical scavenging both by steady state and time resolved methods such as nanosecond pulse radiolysis and stopped-flow spectrophotometric analyses. FRE exhibited significantly higher steady state antioxidant activity than FRW. FRE exhibited concentration dependent DPPH, ABTS•−, hydroxyl radical and superoxide radical scavenging and inhibition of lipid peroxidation with IC50 comparable with tested standard compounds. In vitro radioprotective potential of FRE was studied using micronucleus assay in irradiated Chinese hamster lung fibroblast cells (V79). Pretreatment with different doses of FRE 1h prior to 2 Gy γ-radiation resulted in a significant (P < 0.001) decrease in the percentage of micronucleated binuclear V79 cells. Maximum radioprotection was observed at 20 μg/ml of FRE. The radioprotection was found to be significant (P < 0.01) when cells were treated with optimum dose of FRE (20 μg/ml) 1 h prior to 0.5, 1, 2, 3 and 4 Gy γ-irradiation compared to the respective radiation controls. The cytokinesis-block proliferative index indicated that FRE does not alter radiation induced cell cycle delay. Based on all these results we conclude that the ethanol extract of F. racemosa acts as a potent antioxidant and a probable radioprotector

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM (-/-) patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Energy Security as a Priority for CEE Countries. Is the King Naked?

The aim of this article is to assess the implementation process of the EU energy security policy in Central and Eastern European (CEE) countries. In the EU, energy security remains a crucial issue for European Energy Strategy, the fundamental goals of which include the security of supply, sustainability and competitiveness. Security of supply should be considered the most important aspect in this context, because it is connected to deep interdependencies between markets and economies, often based on political or even geo-political considerations. This is currently particularly noticeable, among other things, in the relations between the EU and Russia, where – in the event of any potential energy supply disturbances – some CEE countries are considered to be the most exposed. By analysing matters referred to the security of energy supplies, the article aims to determine the scope of activities undertaken by selected CEE countries which are also EU Member States in order to achieve this goal. The paper stresses the significance of cooperation by CEE countries at regional level, and focuses on initiatives and projects meant to ensure the security of their energy supplies. The conclusions of the paper assess some of the success stories as well as failures experienced by CEE countries in the process of building their energy independence.Le but de cet article est d'évaluer la mise en oeuvre de la politique de sécurité énergétique de l’Union européenne dans les pays de l’Europe centrale et orientale (PECO). Dans l'UE, la sécurité énergétique est un enjeu crucial pour la Stratégie énergétique européenne qui contient parmi ces objectifs fondamentaux la sécurité de l'approvisionnement, la durabilité et la compétitivité. La sécurité de l’approvisionnement doit être considérée comme l'aspect le plus important dans ce contexte, car elle est liée aux interdépendances profondes entre les marchés et les économies, souvent basées sur des considérations politiques ou même géo-politiques. Ceci est actuellement particulièrement visible, entre autres, dans les relations entre l'UE et la Russie, où - dans le cas de perturbations concernant l'approvisionnement en énergie - certains PECO sont considérés comme le plus exposés. En analysant les questions concernant la sécurité de l’approvisionnement énergétique, l'article vise à déterminer l’étendue des activités entreprises par certains PECO [qui sont aussi les États Membres de l’Union européenne] afin d’atteindre cet objectif. L’article souligne l'importance de la coopération des PECO au niveau régional et se focalise sur les initiatives et les projets visés à assurer la sécurité de l’approvisionnement énergétique de ces pays. Les conclusions de cet article évaluent des réussites, ainsi que les échecs des PECO, dans le processus de la construction de leur indépendance énergétique

Histone H2AX and Fanconi anemia FANCD2 function in the same pathway to maintain chromosome stability

Fanconi anemia (FA) is a chromosome fragility syndrome characterized by bone marrow failure and cancer susceptibility. The central FA protein FANCD2 is known to relocate to chromatin upon DNA damage in a poorly understood process. Here, we have induced subnuclear accumulation of DNA damage to prove that histone H2AX is a novel component of the FA/BRCA pathway in response to stalled replication forks. Analyses of cells from H2AX knockout mice or expressing a nonphosphorylable H2AX (H2AX(S136A/S139A)) indicate that phosphorylated H2AX (γH2AX) is required for recruiting FANCD2 to chromatin at stalled replication forks. FANCD2 binding to γH2AX is BRCA1-dependent and cells deficient or depleted of H2AX show an FA-like phenotype, including an excess of chromatid-type chromosomal aberrations and hypersensitivity to MMC. This MMC hypersensitivity of H2AX-deficient cells is not further increased by depleting FANCD2, indicating that H2AX and FANCD2 function in the same pathway in response to DNA damage-induced replication blockage. Consequently, histone H2AX is functionally connected to the FA/BRCA pathway to resolve stalled replication forks and prevent chromosome instability