HOW SELENIUM MODIFIES CROSS-TALK BETWEEN THE PIKK FAMILY AND INSIGHTS ON THE REGULATION OF DNA-PKcs

We recently found that ATM is required for a selenium-induced senescence response in non-cancerous cells. We hypothesize the selenium-induced DNA damage response modifies ATM and DNA-PKcs cross-talk. Phospho-specific antibodies against ATM and DNA-PKcs were used to follow the phosphorylation events after selenium treatment in normal human cells and two human cancer cell lines. Results from immunofluorescence analysis showed that selenium treatment induces hyperphosphorylation of DNA-PKcs at T2647 and S2056 in non-cancerous MRC-5 cells but not in U-2 OS cancer cells. Further studies in MRC-5 cells treated with an ATM kinase inhibitor, KU 55933, showed attenuation of the selenium-induced DNA-PKcs phosphorylation at both foci, whereas pre-treatment with a DNA-PKcs kinase inhibitor, NU 7026, does not prevent ATM phosphorylation at S1981, an event leading to ATM pathway activation. These results give evidence that DNA-PKcs and ATM have a cooperative role in the DNA damage response pathway

THE ROLE OF ATAXIA TELANGIECTASIA MUTATED AND THE CATALYTIC SUBUNIT OF DNA-DEPENDENT PROTEIN KINASE DURING ADIPOGENESIS

Ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs), are DNA damage response (DDR) proteins that have well established roles in the repair of DNA double strand breaks (DSBs). A growing body of scientific evidence suggests that these kinases have important, but not yet well-understood, immune and metabolic functions. ATM and DNA-PKcs can regulate cellular oxidative stress and combat reactive oxygen species (ROS) (Chen et al 2012). Since oxidative stress is a driving factor in the pathogenesis of many obesity related complications, ATM and DNA-PKcs may help respond to and regulate oxidative stress in adipocytes. Precise oxidative signaling is necessary for adipocyte differentiation and lipid accumulation. Selenium, a nutrient with suspected insulin mimetic properties, can alter cellular oxidative stress (H Gandhi et al 2013). Therefore, it is plausible that selenium may affect adipogenesis and change lipid accumulation patterns in cells. The primary research questions were as follows: What is the role of ATM and DNA-PKcs in adipogenesis and adipocyte homeostasis? Are the actions of these kinases in adipocytes explained by changes in oxidative stress levels? Do proposed nutrients with insulin mimetic properties, like selenium, affect adipogenesis via the suspected ATM - DNA-PKcs - ROS pathway? Time dependent mammalian cell culture based experiments that measured outcome variables like lipid accumulation, senescence activity, protein expression and ROS levels were conducted to assess the action of ATM and DNA-PKcs during adipogenesis and the effect of selenium on the ATM - DNA-PKcs - ROS dependent adipogenic pathway. This study found that ATM and DNA-PKcs are necessary proteins for maintaining adipocyte integrity as well as having a significant role in the differentiation of preadipocyte to adipocyte. Furthermore, we confirmed that the kinases act via a ROS dependent pathway and that dietary nutrients, such as selenium, can exert additional control over this pathway, therefore highlighting the impact adipocyte metabolism exerts over total metabolic health

Influence of the geometry of protective barriers on the propagation of shock waves

International audienceThe protection of industrial facilities, classified as hazardous, against accidental or intentional explosions represents a major challenge for the prevention of personal injury and property damage, which also involves social and economic issues. We consider here the use of physical barriers against the effects of these explosions, which include the pressure wave, the projection of fragments and the thermal flash. This approach can be recommended for the control of major industrials risks, but no specific instructions are available for its implementation. The influence of a protective barrier against a detonation-type explosion is studied in small-scale experiments. The effects of overpressure are examined over the entire path of the shock wave across the barrier and in the downstream zone to be protected. Two series of barrier structures are studied. The first series (A) of experiments investigates two types of barrier geometry with dimensions based on NATO recommendations. These recommendations stipulate that the barrier should be 2 m higher than the charge height, the thickness at the crest should be more than 0.5 m, while its length should be equal to twice the protected structure length and the bank slope should be equivalent to the angle of repose of the soil. The second series (B) of experiments investigates the influence of geometrical parameters of the barrier (thickness at the crest and inclination angles of the front and rear faces) on its protective effects. This project leads to an advance in our understanding of the physical phenomena involved in the propagation of blast waves resulting from an external explosion, in the area around a protective physical barrier. The study focuses on the dimensioning of protective barriers against overpressures effects arising from detonation and shows the advantage of using a barrier with a vertical front or rear face

Caractérisation d’un mastic prêt à l’emploi peu connu pour le comblement superficiel des céramiques : le Flügger Filler Interior

Le comblement des manques superficiels (éclats, manques le long des lignes de cassure) est une problématique récurrente en restauration de céramiques. Dans la pratique, les restaurateurs utilisent certains produits prêts à l’emploi, parmi lesquels le Modostuc et le Flügger Filler Interior, car ils sont très faiblement toxiques et d’une mise-en-œuvre aisée. La perception des utilisateurs, lors de l’emploi de ces deux produits, laisse présumer certaines différences, notamment au niveau de leur rugosité, de leur dureté et de leur adhérence à la pâte céramique. L’objet de cette étude est de mettre en place une procédure expérimentale simple et adaptée permettant de différencier, par la mesure, les propriétés mécaniques de ces produits. Les résultats obtenus indiquent clairement des dissimilitudes et pourront servir de base dans le choix du produit le plus adapté à chaque céramique traitée.Filling in superficial gaps (chips, losses along cracks) is a recurrent problem in ceramic restoration. In practice, restorers employ certain ready-to-use products, among which are Modostuc and Flügger Filler Interior, because they have low toxicity and are easy to use. While employing these two products, users noticed differences, particularly in their roughness, hardness and adhesion to the ceramic. The purpose of this study was to establish a simple, specially adapted, experimental procedure enabling us to differentiate, by measuring, the mechanical properties of these products. The results obtained clearly indicated the differences and may now serve as a basis for choosing the most suitable product to use on each ceramic in need of restoration

Effect of prevention measures on incidence of human listeriosis, France, 1987-1997.

To assess the impact of preventive measures by the food industry, we analyzed food monitoring data as well as trends in the incidence of listeriosis estimated through three independent sources: the National Reference Center of Listeriosis; a laboratory-based active surveillance network; and two consecutive nationwide surveys of public hospital laboratories. From 1987 to 1997, the incidence of listeriosis decreased by an estimated 68%. A substantial reduction in the proportion of Listeria monocytogenes-contaminated products was observed at the retail level. The temporal relationship between prevention measures by the food industry, reduction in L. monocytogenes-contaminated foodstuffs, and reduction in listeriosis incidence suggests a causal relationship and indicates that a substantial part of the reduction in illness is related to prevention efforts

Concurrent Conditions and Human Listeriosis, England, 1999–2009

The epidemiology of listeriosis in England and Wales changed during 2001–2008; more patients >60 years of age had bacteremia than in previous years. To investigate these changes, we calculated risk for listeriosis by concurrent condition for non–pregnancy-associated listeriosis cases reported to the national surveillance system in England during 1999–2009. Conditions occurring with L. monocytogenes infection were coded according to the International Classification of Diseases, 10th Revision, and compared with appropriate hospital episode statistics inpatient denominator data to calculate incidence rates/million consultations. Malignancies (especially of the blood), kidney disease, liver disease, diabetes, alcoholism, and age >60 years were associated with an increased risk for listeriosis. Physicians should consider a diagnosis of listeriosis when treating patients who have concurrent conditions. Providing cancer patients, who accounted for one third of cases, with food safety information might help limit additional cases

Municipal Wastewater Effluents as a Source of Listerial Pathogens in the Aquatic Milieu of the Eastern Cape Province of South Africa: A Concern of Public Health Importance

We evaluated the effluent quality of an urban wastewater treatment facility in South Africa and its impact on the receiving watershed for a period of 12 months. The prevalence and antimicrobial susceptibility of potential Listeria pathogens (L. ivanovii and L. innocua) and the physicochemical quality of the treated wastewater effluent was assessed, with a view to ascertain the potential health and environmental hazards of the discharged effluent. Total listerial density varied between 2.9 × 100 and 1.2 × 105 cfu/mL; free living Listeria species were more prevalent (84%), compared to Listeria species attached to planktons (59–75%). The treated effluent quality fell short of recommended standards for turbidity, dissolved oxygen, chemical oxygen demand, nitrite, phosphate and Listeria density; while pH, temperature, total dissolved solids and nitrate contents were compliant with target quality limits after treatment. The Listeria isolates (23) were sensitive to three (15%) of the 20 test antibiotics, and showed varying (4.5–91%) levels of resistance to 17 antibiotics. Of seven resistance gene markers assayed, only sulII genes were detected in five (22%) Listeria strains. The study demonstrates a potential negative impact of the wastewater effluent on the receiving environment and suggests a serious public health implication for those who depend on the receiving watershed for drinking and other purposes