Hepatic Proteome Analysis of Atlantic Salmon (Salmo salar) After Exposure to Environmental Concentrations of Human Pharmaceuticals

Pharmaceuticals are pseudopersistent aquatic pollutants with unknown effects at environmentally relevant concentrations. Atlantic salmon (Salmo salar) were exposed to Acetaminophen: 54.77 ± 34.67; Atenolol: 11.08 ± 7.98, and Carbamazepine: 7.85 ± 0.13 μg·L−1for 5 days. After Acetaminophen treatment, 19 proteins were differently expressed, of which 11 were significant with respect to the control group (eight up-regulated and three down-regulated). After Atenolol treatment, seven differently expressed proteins were obtained in comparison with the control, of which six could be identified (four up-regulated and two down-regulated). Carbamazepine exposure resulted in 15 differently expressed proteins compared with the control, with 10 of them identified (seven up-regulated and three down-regulated). Out of these, three features were common between Acetaminophen and Carbamazepine and one between Carbamazepine and Atenolol. One feature was common across all treatments. Principal component analysis and heat map clustering showed a clear grouping of the variability caused by the applied treatments. The obtained data suggest (1) that exposure to environmentally relevant concentrations of the pharmaceuticals alters the hepatic protein expression profile of the Atlantic salmon; and (2) the existence of treatment specific processes that may be useful for biomarker development

Occurrence and Effects of Antimicrobials Drugs in Aquatic Ecosystems

Currently, thanks to the development of sensitive analytical techniques, the presence of different emerging pollutants in aquatic ecosystems has been evidenced; however, most of them have not been submitted to any regulation so far. Among emerging contaminants, antimicrobials have received particular attention in recent decades, mainly due to the concerning development of antibiotic resistance observed in bacteria, but little is known about the toxicological and ecological impact that antimicrobials can have on aquatic ecosystems. Their high consumption in human and veterinary medicine, food-producing animals and aquaculture, as well as persistence and poor absorption have caused antimicrobials to be discharged into receiving waters, with or without prior treatment, where they have been detected at ng-mg L-1 levels with the potential to cause effects on the various organisms living within aquatic systems. This review presents the current knowledge on the occurrence of antimicrobials in aquatic ecosystems, emphasizing their occurrence in different environmental matrixes and the effects on aquatic organisms (cyanobacteria, microalgae, invertebrates and vertebrates)

Multi-omic approach to evaluate the response of gilt-head sea bream (Sparus aurata) exposed to the UV filter sulisobenzone

Sulisobenzone (BP-4) is one of the benzophenone type UVfiltersmost frequently detected in aquatic ecosystems. As a suspected endocrine disrupting compound, scarce information is available yet about other molecular effects and its mechanismof action. Here, we used an integrated transcriptomic and metabolomic approach to improve the current understanding on the toxicity of BP-4 towards aquatic species. Gilt-head sea bream individualswere exposed at environmentally relevant concentrations (10 μg L-1) for 22 days. Transcriptomic analysis revealed 371 differentially expressed genes in liver while metabolomic analysis identified 123 differentially modulated features in plasma and 118 in liver. Integration of transcriptomic and metabolomic data showed disruption of the energy metabolism(>10 pathways related to the metabolismof amino acids and carbohydrateswere impacted) and lipid metabolism (5 glycerophospholipids and the expression of 3 enzymes were affected), suggesting oxidative stress.We also observed, for the first time in vivo and at environmental relevant concentrations, the disruption of several enzymes involved in the steroid and thyroid hormones biosynthesis. DNA and RNA synthesis was also impacted by changes in the purine and pyrimidine metabolisms. Overall, the multiomic workflow presented here increases the evidence on suspected effects of BP-4 exposure and identifies additional modes of action of the compounds that could have been overlooked by using single omic approaches. ©2021 The Authors. Published by Elsevier B.V.This research was supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) (CTM2015-70731-R) and the FPI fellowship (BES-2016-078593). The authors also would like to acknowledge the Laboratory of Aquaculture at the Faculty of Marine and Environmental Sciences (University of Cádiz), Thibaut Dumas and David Rosain (UMR HydroSciences, Université Montpellier, France) for their support

Improving the WFD purposes by the incorporation of ecotoxicity tests

Trabajo presentado en la 4th SCARCE International Conference (Towards a better understanding of the links between stressors, hazard assessment and ecosystem services under water scarcity), celebrada en Cádiz el 25 y 26 de noviembre de 2013.The approval of the European Water Framework Dir ective (WFD) supposed a big step regarding aquatic ecosystems protection. According to this Directive, assessment of ecological status is based on three quality elements: biological, physicoc hemical and hydromorphological, but ecotoxicological status is still not included. Some studies have observed that biol ogical status is not always in coherence with physicochemical status, maybe due to the adaptati on mechanisms of aquatic organisms under chronic chemical exposure. In these situations, ecotoxicity t ests could be useful to obtain a better characterisation of these specific ecosystems. The general aim of this work is to add a battery of ecotoxicity tests to the current analyses defined by WFD in order to obtain a better ecological characteriza tion of freshwater systems. The specific aims of this work are: (1) to compare the effectiveness and viability of differen t ecotoxicity tests performed with freshwater sediments (directly and with pore water) ta king as target organisms different aquatic species, and (2) to evaluate the relationship between stream pollutants concentrations (organic pollutants and metals), biological and hydromorphological status and sediments ecotoxicity. For this purpose, thirteen sampling sites within the Ebro river watershed were selected. Data about priority pollutants in water, sediment and fish as well as biological and hydromor phological status of each sampling point will be achieved. Moreover, in each sampling reach, composite samples of sediment were collected by using a Van Veen grab. Sediment samples were stored at 4ºC prior to the ecotoxicity analysesThe ecotoxicity of pore water was evaluated by different bioassays ( Vibrio fischeri, Pseudokirshneriella subcapitata and Daphnia magna ) while the ecotoxicity of wh ole sediment was evaluated in Vibrio fischeri, Nitzschia palea and Chironomus riparius In addition, the concentration of total heavy metals and metal bioavailability was calculated by a sequential extraction according to the Community Bureau of Reference (BCR) method. To distinguish the potentially toxic fraction associated to heavy metals burden of sediments, an analysis of acid-volatile sulphide (AVS) and simultaneously extracted metals (SEM) was performed. Complementary sediment variables as humi dity, porosity, percentages of fines (<63 μm) organic carbon and organic matter were determined. This study expect to demonstrate that the integr ation of chemical, biological and ecotoxicological analyses could be crucial to unde rstand the hazard of pollutants in aquatic ecosystems, especially, in freshwater sediments. Future research in this area is needed in order to obtain more data and be able to establish a tree decision of freshwater analyses ev aluation. The poster will present the methodology purposed for this study as well as the first prelim inary results obtained from ecotoxicity tests.Authors would like to thank the Spanish Ministry of Economy and Competitiveness for its financial support through the project SCARCE (Consolider-Ingenio 2010 CSD2009-00065Peer Reviewe

Factors Influencing Interdisciplinary Research and Industry-Academia Collaborations at Six European Universities: A Qualitative Study

The introduction of interdisciplinarity and industry-academia collaborations (IAC) into higher education institutions (HEIs) and curricula as tools for promoting sustainable development has been debated both in academic and non-academic contexts. While overall rising trends in the acceptance of interdisciplinarity and IAC exist, research has stressed difficulty in implementation and practices. We conducted eight focus groups at six European Universities (members of the SEA-EU alliance) and analysed the transcripts using Braun and Clarke's reflexive thematic approach to qualitative analysis in order to develop themes on barriers and facilitators to both conducting interdisciplinarity and IAC, as well as the inclusion of university students in interdisciplinary research. We observed that the main barriers to IR and IAC and the inclusion of students in such activities include traditional HEI structures focused on single-discipline approaches, a lack of joint platforms for IR and IAC, and academic differences (publication outcome differences, academic background). Likewise, a lack of funding (especially for early career researchers), employability (for students willing to do a research career), and a lack of validation by HEIs for researchers conducting IR and IAC are major barriers. To IDR- and IAC-related activities, a top-down approach is needed to restructure HEIs and make them more accommodating to both students and staff willing to conduct IR and IAC activities, thus refocusing them towards sustainability

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Effects of environmentally relevant concentrations of pharmaceutical compounds on gene expression in the Gilthead Seabream, Sparus Aurata

Trabajo presentado en el XVI Seminario Ibérico de Química Marina, celebrado en Cádiz del 24 al 26 de enero de 2012.The growing use of pharmaceuticals has become now a new environmental problem which potentially will become dangerous in the future. Due to their high consumption, pharmaceuticals are continuously introduced to sewage waters (excreta, disposal of unused or expired drugs or directly pharmaceutical discharges). As a result, they are found in surface, ground and drinking waters. Non target organisms exposed to these levels of pharmaceuticals may not be affected in survival, but suffer other sublethal effects as a consequence of long term exposure. Individuals of the gilthead seabream, Sparus aurata, were exposed to environmentally relevant concentrations of three representative pharmaceutical compounds, the anti-convulsant drug Carbamazepine (CA), the #12;-blocker Atenolol (AT) and the analgesic Acetaminophen (AC) and susceptible genes were examined for altered expression by means of quantitative real time PCR (qRT-PCR). The study revealed differential, treatment dependent expression of selected target genes showing that environmentally relevant concentrations of these drugs may alter expression patterns compared to nonexposure conditions.Peer Reviewe

Toxicity of Linear Alkylbenzene Sulfonate and One Long-Chain Degradation Intermediate, Sulfophenyl Carboxylic Acid on Early Life-Stages of Seabream (Sparus Aurata)

7 páginas, 3 figuras, 3 tablas.Seabream embryos (Sparus aurata) were exposed to various concentrations (0.05 to 10.0 mg L−1) of different homologues (C10 to C14) and a commercial mixture of linear alkylbenzene sulfonates (LAS), as well as one long-chain degradation intermediate, sulfophenyl carboxylic acid (SPC C11), to study the acute toxicity of these compounds. LAS homologues of higher chain length (C13 and C14) were proved to be more toxic than shorter species (C10, C11, and C12). LAS C13 and C14 provoked 100% lethality at concentrations of 0.1–0.25 mg L−1. On the other hand, shorter LAS homologues (chain length) did not produce any lethal effect at concentrations up to 5 mg L−1. In this work, results on the toxicity of a long-chain degradation intermediate of LAS, SPC C11, are presented. This compound did not produce any mortality at all the concentration ranges chosen.This work has been supported by the Environmental and Climate Program of the European Commission Pristine (Contract ENV4-CT97-494) in the framework of the Waste Water Cluster. We thank the companies Petresa S.A for the LAS supply and "nanical support, and Cupimar S.A. for the seabream egg provision. The long-chain degradation intermediate SPC C 11 was supplied by Dr. GonzaHlez-Mazo. M. Hampel was supported by a fellowship of the CSIC.Peer reviewe