Occurence of legacy and emerging persistent organic pollutants at the Ross Sea and circumpolar deep water convergence (Antarctica)

Persistent organic pollutants (POPs) have attracted the attention of scientists and policy makers in recent decades due to their extreme persistence, semi-volatility, capacity to bio-accumulate in the food chain, and toxic properties. Despite its geographical isolation, extreme meteorological conditions and an almost total absence of local point sources, the Antarctic continent is vulnerable to contamination by POPs, due to the ability of these chemicals to undergo long range atmospheric transport (LRAT) and deposition in the open sea. In a few cases and for limited areas, POPs may be also introduced into the Antarctic ecosystem by human activities (scientific stations, fishing, tourism, accidental oil pills, waste incineration and sewage). Even if various studiesi.e.1,2,3,4,5 have revealed the presence of POPs in air, seawater, sediments and biota in Antarctica, more investigations are needed to implement the number of observations, integrate the data series and meet the indications of the Stockholm Convention and the UNECE protocol in terms of improving knowledge of the temporal and spatial trends of POPs in biotic and abiotic environmental compartments. In this study we present POP concentrations in water samples collected along vertical water columns from seven oceanographic stations located in the Ross Sea and close to the Circumpolar Convergence (see Figure 1). Moreover, the occurrence of emerging and legacy POPs, including polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated naphthalenes (PCNs), organochlorine pesticides (OCPs) and polybrominated diphenylethers (PBDEs) were investigated in order to evaluate their possible sources and relationship with physical and biological processes taking place in the water column. The Ross sea is the formation site of two shelf waters which constitute an important part of the Antarctic Bottom Water (AABWs): the High Salinity Shelf Water (HSSW), which is relatively cold and generated inside the Ross Sea basin and the Ice Shelf Water (ISW). The Ross sea is influenced by only one water mass of external origin, the Circumpolar Deep Water (CDW), which is the largest circulation feature of the Southern Ocean, manly responsible for possible exchange processes between the Antarctic seas and the outer oceans, and thus a possible source of persistent organic pollutants (POPs)2 . The CDW is a relatively warm, salty and nutrient rich water mass carried around Antarctica by the Antarctic Circumpolar Current (ACC)6. Associated with the ACC is the Antarctic Convergence where the cold Antarctic waters meet the warmer waters of the subantarctic creating a zone of upwelling nutrients. Moreover, the Drygalski Glacie Tongue plays an important role in the Polynya development in the Terra Nova Bay, in the Ross sea. An important environmental concern is the accelerated glacier and snow melting that represent a massive release of both naturally occurring chemical substances and organic/inorganic pollutants of anthropogenic origin, which are stored in the deeper layers of the ice and may be delivered to surrounding ecosystems

Functionalized Hyaluronic Acid for “In Situ” Matrix Metalloproteinase Inhibition: A Bioactive Material to Treat the Dry Eye Sydrome

Hyaluronic acid (HA) is a naturally occurring polysaccharide with many molecular functions, including maintaining the structure and physiology of the tissues, tissue remodeling, and inflammation. HA is found naturally in physiological tear fluid, possesses excellent mucus-layer-adhesive properties, and is successfully employed in the treatment of dry eye syndrome (DES). However, HA has as major drawback: its rapid in vivo degradation by hyaluronidase. We report on a unique material, namely, HA-3, obtained by the functionalization of HA with the metalloproteinase inhibitor 3 (MMPI). This material is characterized by an increased resistance to hyaluronidase degradation, associated with MMP inhibition properties. The ability of HA-3 to prevent dehydration of human corneal epithelial cells in vitro and in vivo may accelerate the development of more efficient DES treatment and broaden the application of HA in human diseases

Enrichment, isolation and biodegradation potential of psychrotolerant polychlorinated-​biphenyl degrading bacteria from the Kongsfjorden (Svalbard Islands, High Arctic Norway)

Persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), have been detected in abiotic Arctic matrices: surface sediments and seawater from coastal areas in the Kongsfjorden were collected and analyzed. Levels of PCBs varied depending on the sampling site. Total PCB concentrations were between 11.63 (site C2W) and 27.69 pg l− 1 (site AW). These levels were comparable to those reported previously in lake sediments from the northern Svalbard. The occurrence and biodegradation potential of cold-adapted PCB-oxidizing bacteria in seawater and sediment along the fjord was also evaluated. After enrichment with biphenyl, 246 isolates were obtained with 45 of them that were able to grow in the presence of the PCB mixture Aroclor 1242, as the sole carbon source. The catabolic gene bphA was harbored by 17 isolates with affiliates to the genera Algoriphagus, Devosia and Salinibacterium that have been never reported as able to utilize PCBs, thus deserving further investigation. The total removal of Aroclor 1242 and selected PCB congeners was evaluated at 4 and 15 °C for eight bphA-harboring isolates and Gelidibacter sp. DS-10. With few exceptions, tested strains showed greater efficiency at 15 than at 4 °C. Isolates were able to reduce most chromatographic peaks by > 50%, with some di- and trichlorobiphenyls that were quite totally removed (> 90%)

Ebola Hemorrhagic Fever Transmission and Risk Factors of Contacts, Uganda1

From August 2000 through January 2001, a large epidemic of Ebola hemorrhagic fever occurred in Uganda, with 425 cases and 224 deaths. Starting from three laboratory-confirmed cases, we traced the chains of transmission for three generations, until we reached the primary case-patients (i.e., persons with an unidentified source of infection). We then prospectively identified the other contacts in whom the disease had developed. To identify the risk factors associated with transmission, we interviewed both healthy and ill contacts (or their proxies) who had been reported by the case-patients (or their proxies) and who met the criteria set for contact tracing during surveillance. The patterns of exposure of 24 case-patients and 65 healthy contacts were defined, and crude and adjusted prevalence proportion ratios (PPR) were estimated for different types of exposure. Contact with the patient’s body fluids (PPR = 4.61%, 95% confidence interval 1.73 to 12.29) was the strongest risk factor, although transmission through fomites also seems possible

Chloride intracellular channel 1 activity is not required for glioblastoma development but its inhibition dictates glioma stem cell responsivity to novel biguanide derivatives

Background: Chloride intracellular channel-1 (CLIC1) activity controls glioblastoma proliferation. Metformin exerts antitumor effects in glioblastoma stem cells (GSCs) inhibiting CLIC1 activity, but its low potency hampers its translation in clinical settings. Methods: We synthesized a small library of novel biguanide-based compounds that were tested as antiproliferative agents for GSCs derived from human glioblastomas, in vitro using 2D and 3D cultures and in vivo in the zebrafish model. Compounds were compared to metformin for both potency and efficacy in the inhibition of GSC proliferation in vitro (MTT, Trypan blue exclusion assays, and EdU labeling) and in vivo (zebrafish model), migration (Boyden chamber assay), invasiveness (Matrigel invasion assay), self-renewal (spherogenesis assay), and CLIC1 activity (electrophysiology recordings), as well as for the absence of off-target toxicity (effects on normal stem cells and toxicity for zebrafish and chick embryos). Results: We identified Q48 and Q54 as two novel CLIC1 blockers, characterized by higher antiproliferative potency than metformin in vitro, in both GSC 2D cultures and 3D spheroids. Q48 and Q54 also impaired GSC self-renewal, migration and invasion, and displayed low systemic in vivo toxicity. Q54 reduced in vivo proliferation of GSCs xenotransplanted in zebrafish hindbrain. Target specificity was confirmed by recombinant CLIC1 binding experiments using microscale thermophoresis approach. Finally, we characterized GSCs from GBMs spontaneously expressing low CLIC1 protein, demonstrating their ability to grow in vivo and to retain stem-like phenotype and functional features in vitro. In these GSCs, Q48 and Q54 displayed reduced potency and efficacy as antiproliferative agents as compared to high CLIC1-expressing tumors. However, in 3D cultures, metformin and Q48 (but not Q54) inhibited proliferation, which was dependent on the inhibition dihydrofolate reductase activity. Conclusions: These data highlight that, while CLIC1 is dispensable for the development of a subset of glioblastomas, it acts as a booster of proliferation in the majority of these tumors and its functional expression is required for biguanide antitumor class-effects. In particular, the biguanide-based derivatives Q48 and Q54, represent the leads to develop novel compounds endowed with better pharmacological profiles than metformin, to act as CLIC1-blockers for the treatment of CLIC1-expressing glioblastomas, in a precision medicine approach

Down-Regulation of Serum/Glucocorticoid Regulated Kinase 1 in Colorectal Tumours Is Largely Independent of Promoter Hypermethylation

Background: We have previously shown that serum/glucocorticoid regulated kinase 1 (SGK1) is down-regulated in colorectal cancers (CRC) with respect to normal tissue. As hyper-methylation of promoter regions is a well-known mechanism of gene silencing in cancer, we tested whether the SGK1 promoter region was methylated in colonic tumour samples. Methodology/Principal Findings: We investigated the methylation profile of the two CpG islands present in the promoter region of SGK1 in a panel of 5 colorectal cancer cell lines by sequencing clones of bisulphite-treated DNA samples. We further confirmed our findings in a panel of 10 normal and 10 tumour colonic tissue samples of human origin. We observed CpG methylation only in the smaller and more distal CpG island in the promoter region of SGK1 in both normal and tumour samples of colonic origin. We further identified a single nucleotide polymorphism (SNP, rs1743963) which affects methylation of the corresponding CpG. Conclusions/Significance: Our results show that even though partial methylation of the promoter region of SGK1 is present

Rôle des voies de réponse au stress dans le maintien de la stabilité génomique chez la levure Schizosaccharomyces pombe

Le génome est sans cesse menacé dans sa structure par des stress génotoxiques d origine endogène (stress oxydant, blocage de la réplication ) ou exogène (irradiations, produits chimiques, métaux lourds ). La voie de réponse aux dommages de l ADN coordonne un réseau d événements en cascades qui incluent les points de surveillance du cycle cellulaire, la réplication/réparation/recombinaison de l ADN et la mort cellulaire programmée. Ces voies collaborent pour assurer la transmission fidèle du génome et empêcher la prolifération des cellules qui aurait accumulé des altérations génétiques. En général, des défauts dans une de ces voies entraînent un changement de sensibilité aux agents génotoxiques, une instabilité génétique et une prédisposition au cancer. La recombinaison homologue (RH) est une voie essentielle pour la réparation de l ADN ; elle joue un rôle fondamental dans le maintien de la stabilité du génome. Le stress oxydant, résultant d une augmentation de la concentration intracellulaire de ERO, est une des causes majeures de dommages aux lipides, aux protéines et à l ADN et pour cela, il représente un défi pour la survie cellulaire et pour la stabilité du génome. Les ERO apparaissent physiologiquement lors de la respiration cellulaire ou résultent d un stress environnemental, comme l exposition aux radiations UV ou agents chimiques oxydants. Elles contribuent à certains processus comme la croissance cellulaire, l activité et au repliement des protéines, la sénescence et la mort cellulaire programmée. Il est important de souligner qu un état redox altéré est souvent associé à un fonctionnement anormal des cellules, comme il est observé pour les cellules cancéreuses et les cellules sénescentes. L objectif de ce projet a été d analyser l interface entre les voies DDR et SAPK (Stress activated protein kinase) évolutivement conservées et d en étudier les conséquences sur la stabilité du génome en utilisant comme organisme modèle la levure à fission. Nos résultats montrent que la voie SAPK joue un rôle sur la RH en promouvant la phosphorylation de Rad52, une protéine impliquée dans différentes sous-voies de la RH. Nous avons aussi montré que Rad52 est phosphorylée sur différents acides aminés, parmi lesquels certains sont les cibles de kinases inconnues qui n ont aucun lien avec la voie SAPK. Nous avons observé que Rad52 est phosphorylée soit après un stress oxydant, soit dans des cellules génétiquement sujettes à des perturbations de la RH. Nous avons identifié deux sites de phosphorylation de la protéine Rad52, dont un seul est dépendant de la voie SAPK. En étudiant la phosphorylation de Rad52 dans les cellules invalidées pour la voie SAPK ou mutées pour un des sites de phosphorylation de Rad52, nous avons pu montrer que la RH est modulée par la voie SAPK même en absence de insulte externe. Notre travail ouvre le chemin vers une nouvelle compréhension des mécanismes fondamentaux du maintien de l intégrité du génome.Genomes are routinely submitted to injuries from either endogenous stress (oxidative stress, DNA replication block ) or from exogenous sources (radiations, chemicals, heavy metals ). The DNA damage response (DDR) coordinates a network of pathways including cell cycle checkpoints, DNA replication/repair/recombination, and programmed cell death, ensuring faithful genome transmission and preventing from the proliferation of cells bearing genetic alterations. Defect in one of these pathways generally results in altered sensitivity to genotoxins, genetic instability and cancer predisposition. Homologous recombination (HR) is an essential DNA repair pathway playing pivotal role to maintain genome stability.Oxidative stress, resulting from increased intracellular concentration of ROS, is one of the major causes of lipid, protein and DNA damage, and therefore a challenge for cell survival and genome stability. ROS are generated physiologically as by-products of cellular respiration, or as result of environmental stresses, such as exposure to solar UV radiations or to oxidant chemicals, and they actively participate in processes such as cellular growth, protein activity and folding, senescence and programmed cell death. It is noteworthy that an altered redox homeostasis is often associated to abnormally functioning cells, such as cancer and senescent cells. The aim of this project was to study the interface between two major evolutionarily conserved pathways, DDR and SAPK (Stress activated protein kinase) and the consequences on genome stability using fission yeast as a model organism. We report data showing that SAPK pathway impinges on HR by promoting phosphorylation of Rad52, a key protein involved in all sub-pathways of HR. We also revealed that Rad52 is phosphorylated at multiple different sites some of which are substrate for unidentified kinases unrelated to the SAPK pathway. Rad52 phosphorylation occurs either after oxidative stress or in cells genetically prone to HR perturbation. We identified two sites of phosphorylation, one of which is dependent on functional SAPK pathway. By studying Rad52 phosphorylation in cells mutated in the SAPK pathway or mutated at the Rad52 site of phosphorylation, we showed that HR is modulated by SAPK even in the absence of external insults. Our work pave the way to a novel understanding of fundamental mechanisms required for genome integrity maintenance.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Performance Analysis of Hydrofoil Shaped and Bi-Directional Diffusers for Cross Flow Tidal Turbines in Single and Double-Rotor Configurations

With the aim of finding efficient solutions for cross flow turbine (CFT) bi-directional diffusers able to harvest non perfectly rectilinear tidal currents, a 2D CFD analysis of ducted CFTs was carried out with focus on the effects of diffuser shape and yaw angle. The HARVEST hydrofoil shaped diffuser, equipped with a pair of counter-rotating turbines, and a bi-directional symmetrical diffuser were compared in terms of coefficient of power (CP), torque ripple, overall thrust on diffuser and wake characteristics. Slightly better CP were predicted for the symmetrical diffuser, due to the convergent walls that address the flow towards the blade with a greater attack angle during early and late upwind and to the viscous interactions between the turbine wakes and strong vortices shed by the diffuser. A CP’s extraordinary improving resulted when yaw increased up to 22.5° for the hydrofoil shaped and up to 30° for the symmetrical diffuser. Similar behaviour in yawed flows also occurred in case of a ducted single rotor, demonstrating that it is a characteristic of CFTs. The insertion of a straight throat in the diffuser design proved to be an effective way to mitigate torque ripple, but a CP loss is expected