A comparison of biomarker responses in juvenile diploid and triploid African catfish, Clarias gariepinus, exposed to the pesticide butachlor

Influence of waterborne butachlor (BUC), a commonly used pesticide, on morphometric, biochemical, and molecular biomarkers was evaluated in juvenile, full sibling, diploid and triploid African catfish (Clarias gariepinus). Fish were exposed for 21 days to one of three concentrations of BUC [mean measured µg/L: 22, 44 or 60]. Unexposed (control) triploids were heavier and longer and had higher visceral-somatic index (VSI) than diploids. Also, they had lighter liver weight (HSI) and showed lower transcript levels of brain gonadotropin-releasing hormone (GnRH), aromatase (cyp191b) and fushi tarazu-factor (ftz-f1), and plasma testosterone levels than diploids. Butachlor treatments had no effects, in either diploid or triploid fish, on VSI, HSI, weight or length changes, condition factor (CF), levels of plasma testosterone, 17-β estradiol (E2), cortisol, cholesterol, or mRNA levels of brain tryptophan hydroxylase (tph2), forkhead box L2 (foxl2), and 11 β-hydroxysteroid dehydrogenase type 2 (11β-hsd2). Expressions of cyp191b and ftz-f1 in triploids were upregulated by the two highest concentrations of BUC. In diploid fish, however, exposures to all BUC concentrations decreased GnRH transcription and the medium BUC concentration decreased ftz-f1 transcription. Substantial differences between ploidies in basal biomarker responses are consistent with the reported impaired reproductive axis in triploid C. gariepinus. Furthermore, the present study showed the low impact of short term exposure to BUC on reproductive axis in C. gariepinus

Pharmaceuticals and personal care products in the environment: What are the big questions?

Background: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment. Objective: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas. Data sources: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance. Data synthesis: The top 20 priority questions fell into seven categories: a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, d) effects characterization, e) risk and relative risk, f) antibiotic resistance, and g) risk management. Conclusions: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic.Centro de Investigaciones del Medioambient

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Uptake of Sulfate from Ambient Water by Freshwater Animals

To better understand how the sulfate (SO42&minus;) anion may contribute to the adverse effects associated with elevated ionic strength or salinity in freshwaters, we measured the uptake and efflux of SO42&minus; in four freshwater species: the fathead minnow (Pimephales promelas, Teleostei: Cyprinidae), paper pondshell (Utterbackia imbecillis, Bivalvia: Unionidae), red swamp crayfish (Procambarus clarkii, Crustacea: Cambaridae), and two-lined mayfly (Hexagenia bilineata, Insecta: Ephemeridae). Using &delta;(34S/32S) stable isotope ratios and the concentrations of S and SO42&minus;, we measured the SO42&minus; influx rate (Jin), net flux (Jnet), and efflux rate (Jout) during a 24 h exposure period. For all four species, the means of Jin for SO42&minus; were positive, and Jin was significantly greater than 0 at both target SO42&minus; concentrations in the fish and mollusk and at the lower SO42&minus; concentration in the crayfish. The means of Jout and Jnet were much more variable than those for Jin, but several species by target SO42&minus; concentration combinations for Jout and Jnet, were negative, which suggests the net excretion of SO42&minus; by the animals. The results of our experiments suggest a greater regulation of SO42&minus; in freshwater animals than has been previously reported

Persistent organic pollutants in fish tissue in the mid-continental great rivers of the United States

Great rivers of the central United States (Upper Mississippi, Missouri, and Ohio rivers) are valuable economic and cultural resources, yet until recently their ecological condition has not been well quantified. In 2004– 2005, as part of the Environmental Monitoring and Assessment Program for Great River Ecosystems (EMAPGRE), we measured legacy organochlorines (OCs) (pesticides and polychlorinated biphenyls, PCBs) and emerging compounds (polybrominated diphenyl ethers, PBDEs) in whole fish to estimate human and wildlife exposure risks from fish consumption. PCBs, PBDEs, chlordane, dieldrin and dichlorodiphenyltrichloroethane (DDT) were detected in most samples across all rivers, and hexachlorobenzene was detected in most Ohio River samples. Concentrations were highest in the Ohio River, followed by the Mississippi and Missouri Rivers, respectively. Dieldrin and PCBs posed the greatest risk to humans. Their concentrations exceeded human screening values for cancer risk in 27–54% and 16–98% of river km, respectively. Chlordane exceeded wildlife risk values for kingfisher in 11–96% of river km. PBDE concentrations were highest in large fish in the Missouri and Ohio Rivers (mean \u3e1000 ng g−1 lipid), with congener 47 most prevalent. OC and PBDE concentrations were positively related to fish size, lipid content, trophic guild, and proximity to urban areas. Contamination of fishes by OCs is widespread among great rivers, although exposure risks appear to be more localized and limited in scope. As an indicator of ecological condition, fish tissue contamination contributes to the overall assessment of great river ecosystems in the U.S

EFFECTS FROM FILTRATION, CAPPING AGENTS, AND PRESENCE/ABSENCE OF FOOD ON THE TOXICITY OF SILVER NANOPARTICLES TO \u3ci\u3eDAPHNIA MAGNA\u3c/i\u3e

Relatively little is known about the behavior and toxicity of nanoparticles in the environment. Objectives of work presented here include establishing the toxicity of a variety of silver nanoparticles (AgNPs) to Daphnia magna neonates, assessing the applicability of a commonly used bioassay for testing AgNPs, and determining the advantages and disadvantages of multiple characterization techniques for AgNPs in simple aquatic systems. Daphnia magna were exposed to a silver nitrate solution and AgNPs suspensions including commercially available AgNPs (uncoated and coated), and laboratory-synthesized AgNPs (coated with coffee or citrate). The nanoparticle suspensions were analyzed for silver concentration (microwave acid digestions), size (dynamic light scattering and electron microscopy), shape (electron microscopy), surface charge (zeta potentiometer), and chemical speciation (X-ray absorption spectroscopy, X-ray diffraction). Toxicities of filtered (100 nm) versus unfiltered suspensions were compared. Additionally, effects from addition of food were examined. Stock suspensions were prepared by adding AgNPs to moderately hard reconstituted water, which were then diluted and used straight or after filtration with 100-nm filters. All nanoparticle exposure suspensions, at every time interval, were digested via microwave digester and analyzed by inductively coupled argon plasma–optical emission spectroscopy or graphite furnace– atomic absorption spectroscopy. Dose–response curves were generated and median lethal concentration (LC50) values calculated. The LC50 values for the unfiltered particles were (in μ/L): 1.1±0.1-AgNO3; 1.0±0.1-coffee coated; 1.1±0.2-citrate coated; 16.7±2.4 Sigma Aldrich Ag-nanoparticles (SA) uncoated; 31.5±8.1 SA coated. LC50 values for the filtered particles were (in μ/L): 0.7±0.1- AgNO3; 1.4±0.1-SA uncoated; 4.4±1.4-SA coated. The LC50 resulting from the addition of food was 176.4±25.5-SA coated. Recommendations presented in this study include AgNP handling methods, effects from sample preparation, and advantages/ disadvantages of different nanoparticle characterization techniques

Statistical Survey of Persistent Organic Pollutants: Risk Estimations to Humans and Wildlife through Consumption of Fish from U.S. Rivers

U.S. EPA conducted a national statistical survey of fish tissue contamination at 540 river sites (representing 82 954 river km) in 2008–2009, and analyzed samples for 50 persistent organic pollutants (POPs), including 21 PCB congeners, 8 PBDE congeners, and 21 organochlorine pesticides. The survey results were used to provide national estimates of contamination for these POPs. PCBs were the most abundant, being measured in 93.5% of samples. Summed concentrations of the 21 PCB congeners had a national weighted mean of 32.7 μg/kg and a maximum concentration of 857 μg/kg, and exceeded the human health cancer screening value of 12 μg/kg in 48% of the national sampled population of river km, and in 70% of the urban sampled population. PBDEs (92.0%), chlordane (88.5%) and DDT (98.7%) were also detected frequently, although at lower concentrations. Results were examined by subpopulations of rivers, including urban or nonurban and three defined ecoregions. PCBs, PBDEs, and DDT occur at significantly higher concentrations in fish from urban rivers versus nonurban; however, the distribution varied more among the ecoregions. Wildlife screening values previously published for bird and mammalian species were converted from whole fish to fillet screening values, and used to estimate risk for wildlife through fish consumption