Faster Atlantic currents drive poleward expansion of temperate phytoplankton in the Arctic Ocean.

The Arctic marine biome, shrinking with increasing temperature and receding sea-ice cover, is tightly connected to lower latitudes through the North Atlantic. By flowing northward through the European Arctic Corridor (the main Arctic gateway where 80% of in- and outflow takes place), the North Atlantic Waters transport most of the ocean heat, but also nutrients and planktonic organisms toward the Arctic Ocean. Using satellite-derived altimetry observations, we reveal an increase, up to two-fold, in North Atlantic current surface velocities over the last 24 years. More importantly, we show evidence that the North Atlantic current and its variability shape the spatial distribution of the coccolithophore Emiliania huxleyi (Ehux), a tracer for temperate ecosystems. We further demonstrate that bio-advection, rather than water temperature as previously assumed, is a major mechanism responsible for the recent poleward intrusions of southern species like Ehux. Our findings confirm the biological and physical "Atlantification" of the Arctic Ocean with potential alterations of the Arctic marine food web and biogeochemical cycles.

[Pharmaceutical consultations in oncology: Implementation, one-year review and outlooks]. / Consultations pharmaceutiques en oncologie : mise en place, bilan à un an et perspectives.

OBJECTIVES: The oral route is becoming increasingly important in the panel of anti-cancer therapeutics, but it generates difficulties (adherence, management of adverse effects...). In order to secure medication management, the pharmaceutic team chose to set up pharmaceutical consultations. Its objectives are multiple: understanding of treatment for better adherence, pharmaceutical analysis, enhancement of the city-hospital link. This work presents the setting up of the pharmaceutical consultations and makes an assessment after one year. METHODS: The initial step was a meeting with institutional health professionals who work with patients to define the place, the objectives, and the patients targeted by the pharmaceutical consultation. The targeted patients are all patients receiving temozolomide and some patients initiating oral chemotherapy, considered at risk, on medical solicitation. Documents were created to standardize practices in the team from the collection of information and pharmaceutical analysis until the conduct of the consultation and the consultation report (integrated into the computerized patient's medical file). Activity indicators were defined and collected. RESULTS: Over one year, 65 pharmaceutical consultations were conducted, of which 23 % resulted in pharmaceutical interventions. The average duration of consultation was 34minutes. The whole team (four pharmacists and two residents) was involved in this activity. CONCLUSIONS: Pharmaceutical consultations help secure medical care of patients, providing tools, dedicated and personalized time, pharmaceutical analysis, etc. Ultimately, the goal is to accompany the patient throughout his treatment by having follow-up pharmaceutical consultations, in collaboration with community pharmacists thanks to the city-hospital link that we have established.

Ballasting by cryogenic gypsum enhances carbon export in a Phaeocystis under-ice bloom.

Mineral ballasting enhances carbon export from the surface to the deep ocean; however, little is known about the role of this process in the ice-covered Arctic Ocean. Here, we propose gypsum ballasting as a new mechanism that likely facilitated enhanced vertical carbon export from an under-ice phytoplankton bloom dominated by the haptophyte Phaeocystis. In the spring 2015 abundant gypsum crystals embedded in Phaeocystis aggregates were collected throughout the water column and on the sea floor at a depth below 2 km. Model predictions supported by isotopic signatures indicate that 2.7 g m-2 gypsum crystals were formed in sea ice at temperatures below -6.5 °C and released into the water column during sea ice melting. Our finding indicates that sea ice derived (cryogenic) gypsum is stable enough to survive export to the deep ocean and serves as an effective ballast mineral. Our findings also suggest a potentially important and previously unknown role of Phaeocystis in deep carbon export due to cryogenic gypsum ballasting. The rapidly changing Arctic sea ice regime might favour this gypsum gravity chute with potential consequences for carbon export and food partitioning between pelagic and benthic ecosystems.

Integrating ecotoxicity and chemical approaches to compare the effects of ZnO nanoparticles, ZnO bulk, and ZnCl2 on plants and microorganisms in a natural soil.

This work compared the toxicity of ZnO nanoparticles (ZnO-NPs), ZnO bulk, and ZnCl2 on microbial activity (C and N transformations and dehydrogenase and phosphatase activities) and their uptake and toxic effects (emergence, root elongation, and shoot growth) on three plant species namely wheat, radish, and vetch in a natural soil at 1000 mg Zn kg(-1). Additionally, plants were also tested at 250 mg Zn kg(-1). The effects of the chemical species on Zn extractability in soil were studied by performing single and sequential extractions. ZnCl2-1000 presented the highest toxicity for both taxonomic groups. For microorganisms, ZnO-NPs demonstrated adverse effects on all measured parameters, except on N transformations. The effects of both ZnO forms were similar. For plants, ZnO-NPs affected the growth of more plant species than ZnO bulk, although the effects were small in all cases. Regarding accumulation, the total Zn amounts were higher in plants exposed to ZnO-NP than those exposed to ZnO bulk, except for vetch shoots. The soil sequential extraction revealed that the Zn concentration in the most labile forms (water soluble (WS) and exchangeable (EX)) was similar in soil treated with ZnO (NP and bulk) and lower than that of ZnCl2-treated soil, indicating the higher availability of the ionic forms. The strong correlations obtained between WS-Zn fraction and the Zn concentrations in the roots, shoots, and the effects on shoot weight show the suitability of this soil extraction method for predicting bioavailable Zn soil for the three plant species when it was added as ZnO-NPs, ZnO bulk, or ZnCl2. In this work, the hazard associated with the ZnO-NPs was similar to ZnO bulk in most cases.

Toxicity of ZnO nanoparticles, ZnO bulk, and ZnCl2 on earthworms in a spiked natural soil and toxicological effects of leachates on aquatic organisms.

The present study assessed the uptake and toxicity of ZnO nanoparticles (NPs), ZnO bulk, and ZnCl2 salt in earthworms in spiked agricultural soils. In addition, the toxicity of aqueous extracts to Daphnia magna and Chlorella vulgaris was analyzed to determine the risk of these soils to the aquatic compartment. We then investigated the distribution of Zn in soil fractions to interpret the nature of toxicity. Neither mortality nor differences in earthworm body weight were observed compared with the control. The most sensitive end point was reproduction. ZnCl2 was notably toxic in eliminating the production of cocoons. The effects induced by ZnO-NPs and bulk ZnO on fecundity were similar and lower than those of the salt. In contrast to ZnO bulk, ZnO-NPs adversely affected fertility. The internal concentrations of Zn in earthworms in the NP group were greater than those in the salt and bulk groups, although bioconcentration factors were consistently <1. No relationship was found between toxicity and internal Zn amounts in earthworms. The results from the sequential extraction of soil showed that ZnCl2 displayed the highest availability compared with both ZnO. Zn distribution was consistent with the greatest toxicity showed by the salt but not with Zn body concentrations. The soil extracts from both ZnO-NPs and bulk ZnO did not show effects on aquatic organisms (Daphnia and algae) after short-term exposure. However, ZnCl2 extracts (total and 0.45-µm filtered) were toxic to Daphnia.

A scalable system for production of functional pancreatic progenitors from human embryonic stem cells.

Development of a human embryonic stem cell (hESC)-based therapy for type 1 diabetes will require the translation of proof-of-principle concepts into a scalable, controlled, and regulated cell manufacturing process. We have previously demonstrated that hESC can be directed to differentiate into pancreatic progenitors that mature into functional glucose-responsive, insulin-secreting cells in vivo. In this study we describe hESC expansion and banking methods and a suspension-based differentiation system, which together underpin an integrated scalable manufacturing process for producing pancreatic progenitors. This system has been optimized for the CyT49 cell line. Accordingly, qualified large-scale single-cell master and working cGMP cell banks of CyT49 have been generated to provide a virtually unlimited starting resource for manufacturing. Upon thaw from these banks, we expanded CyT49 for two weeks in an adherent culture format that achieves 50-100 fold expansion per week. Undifferentiated CyT49 were then aggregated into clusters in dynamic rotational suspension culture, followed by differentiation en masse for two weeks with a four-stage protocol. Numerous scaled differentiation runs generated reproducible and defined population compositions highly enriched for pancreatic cell lineages, as shown by examining mRNA expression at each stage of differentiation and flow cytometry of the final population. Islet-like tissue containing glucose-responsive, insulin-secreting cells was generated upon implantation into mice. By four- to five-months post-engraftment, mature neo-pancreatic tissue was sufficient to protect against streptozotocin (STZ)-induced hyperglycemia. In summary, we have developed a tractable manufacturing process for the generation of functional pancreatic progenitors from hESC on a scale amenable to clinical entry.

Correlation between physicochemical and ecotoxicological approaches to estimate landfill leachates toxicity.

Leachates from municipal solid waste (MSW) landfills may contain a huge diversity of contaminants; these wastewaters should be considered as potentially hazardous complex mixtures, representing a potential environmental risk for surface and groundwater. Current MSW landfill wastes regulatory approaches deem exclusively on the physicochemical characterization and does not contemplate the ecotoxicological assessment of landfill leachates. However, the presence of highly toxic substances in consumer products requires reconsideration on the need of more specific ecotoxicological assessments. The main aim of this study was to evaluate the toxicity of different MSW landfill leachates using a battery of toxicity tests including acute toxicity tests with Daphnia magna and the anuran Xenopus laevis and the in vitro toxicity test with the fish cell line RTG-2. The additional objective was to study the possible correlation between physicochemical properties and the toxicity results obtained for untreated landfill leachates. The results showed that the proposed test battery was effective for the ecotoxicological characterization of MSW landfill leachates. A moderate to strong correlation between the measured physicochemical parameters and the calculated toxicity units was detected for all toxicity assays. Correlation factors of 0.85, 0.86 and 0.55 for Daphnia, Xenopus and RTG-2 tests, respectively, were found. The discriminant analysis showed that certain physicochemical parameters could be used for an initial categorization of the potential aquatic acute toxicity of leachates; this finding may facilitate leachates management as the physicochemical characterization is currently the most common or even only monitoring method employed in a large majority of landfills. Ammonia, alkalinity and chemical oxygen demand (COD), together with chloride, allowed a proper categorization of leachates toxicity for up to 75% of tested samples, with a small percentage of false negatives.

Sewage sludge applied to agricultural soil: Ecotoxicological effects on representative soil organisms.

Application of sewage sludge to agricultural lands is a current practice in EU. European legislation permits its use when concentrations of metals in soil do not increase above the maximum permissible limits. In order to assess the fate and the effects on representative soil organisms of sewage sludge amendments on agricultural lands, a soil microcosm (multi-species soil system-MS3) experiment was performed. The MS3 columns were filled with spiked soil at three different doses: 30, 60 and 120tha(-1) fresh wt. Seed plants (Triticum aestivum, Vicia sativa and Brassica rapa) and earthworms (Eisenia fetida) were introduced into the systems. After a 21-d exposure period, a statistically significant increase for Cd, Cu, Zn and Hg concentrations was found for the soils treated with the highest application rate. Dose-related increase was observed for nickel concentrations in leachates. Plants and earthworm metal body burden offer much more information than metal concentrations and help to understand the potential for metal accumulation. Bioaccumulation factor (BAF(plant-soil)) presented a different behavior among species and large differences for BAF(earthworm-soil), from control or sewage-amended soil, for Cd and Hg were found. B. rapa seed germination was reduced. Statistically significant decrease in fresh biomass was observed for T. aestivum and V. sativa at the highest application rate, whereas B. rapa biomass decreased at any application rate. Enzymatic activities (dehydrogenase and phosphatase) as well as respiration rate on soil microorganisms were enlarged.

A derivative of the melanocortin receptor antagonist SHU9119 (PG932) increases food intake when administered peripherally.

Melanocortin receptors are considered promising candidates for the treatment of behavioral and metabolic disorders ranging from obesity to anorexia and cachexia. These experiments examined the response of mice to peripheral injections of two compounds. PG932 is a derivative of SHU9119 which is non-selective antagonist of melanocortin-3 and melanocortin-4 receptors (Mc3r and Mc4r). PG946 is a derivative of a hybrid of alpha- and beta-MSH, and is a moderately selective Mc3r antagonist. SHU9119 increases food intake when administered intracerebroventricularly but is without effect when injected into the periphery. In contrast, PG932 was found to be highly effective at stimulating food intake when administered peripherally by intraperitoneal injection. The orexigenic effect of PG932 required functional Mc4r, suggesting that inhibition of this receptor is involved in the stimulation of food intake. PG946 did not significantly affect on feeding behavior. PG932 is thus a useful new compound for studies examining the regulation of appetite and energy balance, and may also prove useful for the treatment of cachectic conditions.

Diet-genotype interactions in the development of the obese, insulin-resistant phenotype of C57BL/6J mice lacking melanocortin-3 or -4 receptors.

Loss of brain melanocortin receptors (Mc3rKO and Mc4rKO) causes increased adiposity and exacerbates diet-induced obesity (DIO). Little is known about how Mc3r or Mc4r genotype, diet, and obesity affect insulin sensitivity. Insulin resistance, assessed by insulin and glucose tolerance tests, Ser(307) phosphorylation of insulin receptor substrate 1, and activation of protein kinase B, was examined in control and DIO wild-type (WT), Mc3rKO and Mc4rKO C57BL/6J mice. Mc4rKO mice were hyperphagic and had increased metabolic efficiency (weight gain per kilojoule consumed) relative to WT; both parameters increased further on high-fat diet. Obesity of Mc3rKO was more dependent on fat intake, involving increased metabolic efficiency. Fat mass of DIO Mc3rKO and Mc4rKO was similar, although Mc4rKO gained weight more rapidly. Mc4rKO develop hepatic insulin resistance and severe hepatic steatosis with obesity, independent of diet. DIO caused further deterioration of insulin action in Mc4rKO of either sex and, in male Mc3rKO, compared with controls, associated with increased fasting insulin, severe glucose intolerance, and reduced insulin signaling in muscle and adipose tissue. DIO female Mc3rKO exhibited very modest perturbations in glucose metabolism and insulin sensitivity. Consistent with previous data suggesting impaired fat oxidation, both Mc3rKO and Mc4rKO had reduced muscle oxidative metabolism, a risk factor for weight gain and insulin resistance. Energy expenditure was, however, increased in Mc4rKO compared with Mc3rKO and controls, perhaps due to hyperphagia and metabolic costs associated with rapid growth. In summary, DIO affects insulin sensitivity more severely in Mc4rKO compared with Mc3rKO, perhaps due to a more positive energy balance.

Cytochrome P4501A induction caused by the imidazole derivative Prochloraz in a rainbow trout cell line.

A variety of aquatic pollutants are able to induce cytochrome P4501A (CYP1A) in fish by ligand binding to the aryl hydrocarbon receptor (AhR). High-affinity AhR ligands are planar aromatic polycyclic molecules such as the prototypical ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The present work investigates the ability of the imidazole derivative, Prochloraz (PRO), to induce CYP1A. Computational studies on the molecular structure of PRO indicated that it is highly unlikely for PRO to have both aromatic rings of the molecule, i.e. the imidazole and the benzene ring, in the same plane. Thus, the possible conformers do not take planar structures, in contrast to the typically planar AhR ligands. Experimentally, the capability of PRO to induce CYP1A was assessed using the rainbow trout liver cell line, RTL-W1, as in vitro model. PRO increased in a concentration-dependent way the catalytic activity of CYP1A (determined as 7-ethoxyresorufin-O-deethylase, EROD, activity) in RTL-W1 cells. The potency of PRO was lower than that of a reference AhR-ligand, beta-naphthoflavone (betaNF). In addition to the catalytic level, PRO activated CYP1A also at the transcriptional level as determined by RT-PCR analysis of CYP1A mRNA. These results indicate that PRO, although its structure is not corresponding to the typical features of CYP1A-inducing AhR ligands, still is able to activate CYP1A expression.

Effects of sulfachlorpyridazine in MS.3-arable land: a multispecies soil system for assessing the environmental fate and effects of veterinary medicines.

A multispecies soil system (MS.3) has been used to evaluate the ecological effects of veterinary pharmaceuticals in soil as a result of routine agricultural practices. Different experimental conditions were tested and the variation of the different parameters was evaluated for a final design. A protocol for the MS.3-arable land is presented here. Emergence of seedlings, plant elongation and biomass, earthworm mortality, and soil microbial enzymatic activities have been selected as toxicological endpoints for soil organisms. Toxicity tests were conducted with the leachate on aquatic organisms (in vitro fish cell lines, daphnids, and algae). The system was used for assessing the effects of the antimicrobial sulfachlorpyridazine that was tested in triplicate at concentrations of 0.01, 1, and 100 mg/kg. The chemical was mixed uniformly with a 20-cm depth soil column to resemble the distribution of manure within arable soil. Reversible and nonreversible effects on soil enzymatic activities were observed at 1 and 100 mg/kg, respectively. Earthworms were not affected. Significant reduction of plant elongation and biomass was observed at the highest concentration. Degradation and leaching contributed to the dissipation of sulfachlorpyridazine from the soil column. The undiluted leachate was highly toxic to Daphnia magna. The parent chemical was assumed responsible for the leachate toxicity although the role of mobile metabolites could not be excluded fully. No significant effects were observed for green algae Chlorella vulgaris and for the rainbow trout established cell lines RTG-2 (rainbow trout gonads) and RTL-WI (rainbow trout liver). The MS.3 system offers a cost-effective experimental approach to measure simultaneously fate and effects of chemicals on a realistic soil system under controlled laboratory conditions. The advantages of using MS.3-effect endpoints are discussed.

In vitro toxicity of selected pesticides on RTG-2 and RTL-W1 fish cell lines.

The rainbow trout fish cell lines RTG-2 and RTL-W1 were used to determine the cytotoxic effects of the pesticides bifenthrin, cypermethrin, cyhalothrin, lambda-cyhalothrin, quinalphos and chlorpyrifos. Cytotoxicity was measured by EROD and beta-Gal enzymatic activities, the neutral red (NR) uptake assay, and the FRAME KB protein (KBP) assay. The beta-Gal activity was unaffected by the pesticide exposure. The EROD activity was induced by cyhalothrin and lambda-cyhalothrin (RTG-2 and RTL-W1) and by bifenthrin (RTL-W1). Dose dependent inhibition responses were observed for EROD activity in cells exposed to quinalphos (RTL-W1) and chlorpyrifos (RTG-2 and RTL-W1). RTL-W1 offered a better response for EROD induction. The EC50 values on EROD endpoint were more sensitive than NR and KBP. The acute fish toxicity of chlorpyrifos and quinalphos depends highly on the species; the species sensitivity distributions cover several orders of magnitude and the values obtained for EROS were within the lowest part of the reported ranges.

Ecotoxicological assessment of doxycycline in aged pig manure using multispecies soil systems.

This paper assesses the ecotoxicity of the antibiotic doxycycline in aged spiked pig manure using a multispecies soil system (MS 3) covering plants, earthworms and soil microorganisms. The study reproduced realistic exposure conditions, as well as higher exposure doses covering the uncertainty factors typically employed for covering interspecies variability. MS 3, consisting of columns of natural sieved soil assembled with earthworms and seeds from three plant species, were employed. Pig manure was spiked with doxycycline (75 or 7500 microg/ml), aged for 15 days under aerobic/anaerobic conditions and added on top of the soil columns (120 ml/column, equivalent to 220 kgN/ha). Water and doxycycline free manure were used as negative controls. Doxycycline (7500 microg/ml) solution was used as a positive control. No effects on plants or earthworms were observed. Significant effects on soil phosphatase activity, indicating effects on soil microorganisms, were observed at the highest exposure dose, affecting all soil layers in the doxycycline-solution-treated MS 3 (positive control) but only the top layer in the spiked pig manure system. Chemical analysis confirmed the different behavior of doxycycline in both systems (with and without manure) and those effects were observed in soil with measured concentrations over 1 mg/kg soil. The detection of doxycycline in leachates revealed a potential mobility. Leachate concentrations were similar for doxycycline solution and spiked manure treatments.