Biomarkers of Morbid Obesity and Prediabetes by Metabolomic Profiling of Human Discordant Phenotypes

Metabolomic studies aimed to dissect the connection between the development of type 2 diabetes and obesity are still scarce. In the present study, fasting serum from sixty-four adult individuals classified into four sex-matched groups by their BMI [non-obese versus morbid obese] and the increased risk of developing diabetes [prediabetic insulin resistant state versus non-prediabetic non-insulin resistant] was analyzed by LC- and FIA-ESI-MS/MS-driven metabolomic approaches. Altered levels of [lyso]glycerophospholipids was the most specific metabolic trait associated to morbid obesity, particularly lysophosphatidylcholines acylated with margaric, oleic and linoleic acids [lysoPC C17:0: R=-0.56, p=0.0003; lysoPC C18:1: R=-0.61, p=0.0001; lysoPC C18:2 R=-0.64, p<0.0001]. Several amino acids were biomarkers of risk of diabetes onset associated to obesity. For instance, glutamate significantly associated with fasting insulin [R=0.5, p=0.0019] and HOMA-IR [R=0.46, p=0.0072], while glycine showed negative associations [fasting insulin: R=-0.51, p=0.0017; HOMA-IR: R=-0.49, p=0.0033], and the branched chain amino acid valine associated to prediabetes and insulin resistance in a BMI-independent manner [fasting insulin: R=0.37, p=0.0479; HOMA-IR: R=0.37, p=0.0468]. Minority sphingolipids including specific [dihydro]ceramides and sphingomyelins also associated with the prediabetic insulin resistant state, hence deserving attention as potential targets for early diagnosis or therapeutic intervention

Contaminants of emerging concern in the Basque coast (N Spain): Occurrence and risk assessment for a better monitoring and management decisions

The study of the presence in the aquatic environment of certain substances considered as contaminants of emerging concern (CEC) is a preliminary step to the analysis of the possible harmful effects on aquatic ecosystems and the establishment of the corresponding environmental quality standards. In order to monitor the occurrence of CECs in the aquatic environment, the European Commission established in 2015 and 2018 two watch-list of substances for Union-wide monitoring in the field of water policy (Decision (EU) 2015/495 and Decision (EU) 2018/840). In the coast of the Basque Country, southeast of the Bay of Biscay, 19 of these watch list substances were monitored quarterly from May 2017 to March 2019. Water samples were collected at the effluent of three wastewater treatment plants and five control points associated with receiving waters (transitional and coastal water bodies). The most frequently quantified substances were azithromycin (91%), imidacloprid (82%), clarithromycin (80%), diclofenac (78%) and erythromycin (73%), with frequencies of quantification higher in wastewaters (83–100%) than in receiving waters (70–85%). In general, concentrations in wastewater were also higher than in receiving waters, indicating a dilution effect in the environment. In receiving waters, six out of the nineteen substances monitored exceeded their respective Predicted No-Effect Concentrations: azithromycin (34%), imidacloprid (9%), 17β-estradiol (E2) (9%), clarithromycin (7%), ciprofloxacin (7%), and diclofenac (5%); and therefore, their levels could pose an environmental risk.This work was supported by the Basque Water Agency (URA) through the project “Network for monitoring the ecological and chemical status of transitional and coastal waters of the Basque coast”, and partly by the Generalitat de Catalunya (Consolidate Research Group 2017-SGR-14) and the Ministry of Science and Innovation of Spain (Project CEX2018-000794-S). Biotage is acknowledged for the gift of ISOLUTE® Na2SO4 drying cartridges. The authors acknowledge the help of the entities in charge of the management of the three studied WWTPs (Consorcio de Aguas Bilbao Bizkaia, Consorcio de Aguas de Busturialdea and Aguas del Añarbe), as well as the work of all sampling and laboratory technicians. This is contribution number 1002 from the Marine Research of AZTI-BRTA (Basque Research and Technology Alliance).Peer reviewe

Iodinated disinfection byproducts: Formation and concerns

The list of iodinated disinfection byproducts (iodo-DBPs) includes some of the most genotoxic and cytotoxic DBPs discovered to date. Therefore, human exposure should be minimized by reducing their presence in drinking water. In this manuscript we review the main iodo-DBP formation pathways during water disinfection, with focus on the advances reported in the last two years. We discuss the effect of iodine sources other than iodine salts, e.g., iodinated contrast media or iodate, on iodo-DBP formation. In addition, we review the anthropogenic activities (like oil and gas extraction, dairy industry, seawater desalination or advanced oxidation treatments with persulfate) that may release iodo-DBPs to the aquatic environment or increase the potential of source waters to generate these compounds when disinfected

Toxicity tests in wastewater and drinking water treatment processes: A complementary assessment tool to be on your radar

Wastewater discharges from cities and industries, especially megacities, and intensive livestock can be considered as main sources of pollution of our rivers and groundwater. Water pollution, therefore, constitutes a major threat to both aquatic ecosystems and human health. Here we address the influence of chemical pollution in waste- and drinking water, their associated potential toxicological effects, as well as, the available technologies for their removal. This opinion paper provides illustrative selected examples covering a broad range for both drinking water and wastewater treatment processes, for which a battery of toxicity tests is applied for their risk assessment. The examples are classified based on five hot topics: (i) Bioassays for toxicity evaluation, (ii) Toxicity of municipal wastewaters, (iii) Toxicity of pharmaceutical residues and hospital wastewaters, (iv) Toxicity of other non-urban effluent examples, and (v) Drinking water treatment processes and toxicity evaluation. 'Chemical analysis combined with batteries of bioassays covering a broad range of endpoints: cytotoxicity, endocrine disruption, genotoxicity, and other types seem to be good way to assess performance/efficiency of the water treatment processes when removing chemical contaminants.. Altogether, while recognizing that water treatment is a cornerstone for water pollution reduction, providing safe water for both human use and its return back to the aquatic environment will be undoubtedly enhanced with the use of ecotoxicity biomonitoring.This work has been financially supported by the Generalitat de Catalunya (Consolidated Research Group “2017 SGR 1404 - Water and Soil Quality Unit”) and by the Spanish Ministry of Science and Innovation (Project CEX2018-000794-S). The authors would like to thank the reviewers whose valuable comments helped us to improve the manuscript.Peer reviewe

LC-HRMS Suspect Screening for Detection-Based Prioritization of Iodinated Contrast Media Photodegradates in Surface Waters

The objective of the study was to demonstrate the applicability of suspect screening for the detection of six iodinated contrast media (ICM) and their phototransformation products (TPs) in surface waters. First, a photodegradation study of ICM in surface water using a sunlight lab-scale simulator was performed. By means of a guided differential sample analysis, the exact masses of the molecular ions and the retention times of TPs were identified. Positive findings were filtered manually generating a suspect list of 108 photoproducts. Following a generic solid-phase extraction of surface water samples, LC-HRMS was used to screen for the presence of the compounds previously detected in the photodegradation samples. On the basis of detection frequencies (>50% of the samples), 11 TPs were prioritized and their structures elucidated by HRMS and NMR. In the real surface water samples, median concentration of parent compounds was 110 ng/L reaching up to 6 μg/L for iomeprol, while TPs were found at median concentration of 8 ng/L, reaching up to 0.4 μg/L for iomeprol TP651-B. In summary, the proposed screening approach facilitates the evaluation of the degradation of polar compounds at a real scale with a fast detection of TPs without prior availability of the standards

Using MALDI-TOF MS imaging and LC-HRMS for the investigation of the degradation of polycaprolactone diol exposed to different wastewater treatments

Polymers are used in high amounts in a wide range of applications from biomedicine to industry. Because of the growing awareness of the increasing amounts of plastic wastes in the aquatic environment during recent years, the evaluation of their biodegradability deserves special attention. In the past, most efforts were dedicated to studying the biodegradation of polyesters in soil and compost, while very little research has been conducted on their fate in wastewater. Here, we assessed the ability of bacterial communities residing in the aerobic and denitrification tank from a wastewater treatment plant (WWTP) to degrade the polymeric ester polycaprolactone diol (PCLD; average molecular weight of 1250 Da). Following the incubation of the solid polymer in WWTP tanks, matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to provide evidence for hydrolytic reactions and to study differences in the spatial degradation on the PCLD surface. It was demonstrated that regardless of the wastewater type, the chemical structure on the PCLD surface underwent modifications after 7 days of exposure. Apart from the parent PCLD peak series in MALDI-MSI mass spectra, the presence of a second oligomer series with mass peaks spaced by m/z 114 (as in PCLD) was observed. It was proposed to correspond to polycaprolactone (PCL) originating from the hydrolytic cleavage of the diethylene glycol from PCLD. Their ion masses were detected at m/z 104 below the PCLD peaks and their structures were proposed as PCL cyclized oligomers. Differences in the spatial distribution of low MW ions (<800) between the aerobic and denitrifying exposed samples in MALDI MSI were also noticeable. While the ions at m/z 221.1, 247.1 and 449.2 predominated in the aerobic exposed sample, those at m/z 475.5 and 677.4 were characteristic of the denitrifying one. The MALDI-MSI measurements in the low mass range were complemented with LC-HRMS analysis to determine plausible structures of the major degradation products. Ten transformation products (TPs) were detected in the denitrifying wastewater experiment, five of them were the result of ester hydrolysis forming caprolactone oligomers (TPs 220, 334, 448, 562, and 676) while the other series corresponded to formation of PCL chain with a terminal diethylene glycol, likewise formed by ester hydrolysis (TPs 246, 360, 474, 588, and 702). [Figure not available: see fulltext.]. © 2017, The Author(s).This study has been financially supported by the EU through the FP7 project GLOBAQUA (Grant Agreement No 603629), and by the Generalitat de Catalunya (Consolidated Research Groups “2014 SGR 418—Water and Soil Quality Unit” and 2014 SGR 291—ICRA). It reflects only the author’s views. The Community is not liable for any use that may be made of the information contained therein.Peer reviewe

A modified recombineering protocol for the genetic manipulation of gene clusters in Aspergillus fumigatus

© 2014 Alcazar-Fuoli et al. Genomic analyses of fungal genome structure have revealed the presence of physically-linked groups of genes, termed gene clusters, where collective functionality of encoded gene products serves a common biosynthetic purpose. In multiple fungal pathogens of humans and plants gene clusters have been shown to encode pathways for biosynthesis of secondary metabolites including metabolites required for pathogenicity. In the major mould pathogen of humans Aspergillus fumigatus, multiple clusters of co-ordinately upregulated genes were identified as having heightened transcript abundances, relative to laboratory cultured equivalents, during the early stages of murine infection. The aim of this study was to develop and optimise a methodology for manipulation of gene cluster architecture, thereby providing the means to assess their relevance to fungal pathogenicity. To this end we adapted a recombineering methodology which exploits lambda phage-mediated recombination of DNA in bacteria, for the generation of gene cluster deletion cassettes. By exploiting a pre-existing bacterial artificial chromosome (BAC) library of A. fumigatus genomic clones we were able to implement single or multiple intra-cluster gene replacement events at both subtelomeric and telomere distal chromosomal locations, in both wild type and highly recombinogenic A. fumigatus isolates. We then applied the methodology to address the boundaries of a gene cluster producing a nematocidal secondary metabolite, pseurotin A, and to address the role of this secondary metabolite in insect and mammalian responses to A. fumigatus challenge.

Antibiotics in the Basque coast (N Spain): Occurrence in waste and receiving waters, and risk assessment (2017-2020)

The study of the presence of antibiotics in the aquatic environment is a preliminary step to analyse their possible harmful effects on aquatic ecosystems. In order to monitor their occurrence in the aquatic environment, the European Commission established in 2015, 2018, and 2020 three Watch Lists of substances for Union-wide monitoring (Decisions (EU) 2015/495, 2018/840, and 2020/1161), where some antibiotics within the classes of macrolides, fluoroquinolones and penicillins were included. In the Basque coast, northern Spain, three macrolide antibiotics (erythromycin, clarithromycin, azithromycin) and ciprofloxacin were monitored quarterly from 2017 to 2020 (covering a period before and after the COVID19 outbreak), in water samples collected from two Waste Water Treatment Plants (WWTPs), and three control points associated with receiving waters (transitional and coastal water bodies). This work was undertaken for the Basque Water Agency (URA). The three macrolide antibiotics in water showed a frequency of quantification >65 % in the Basque coast, with higher concentrations in the WWTP emission stations than in receiving waters. Their frequency of quantification decreased from 2017 to 2020, as did the consumption of antibiotics in Spanish primary care since 2015. Ciprofloxacin showed higher frequencies of quantification in receiving waters than in wastewaters, but the highest concentrations were observed in the WWTP emission stations. Although consumption of fluoroquinolones (among which is ciprofloxacin) in primary care in the Basque Country has decreased in recent years, this trend was not observed in the waters sampled in the present study. On the other hand, concentrations of clarithromycin, azithromycin, and ciprofloxacin in receiving waters exceeded their respective Predicted No-Effect Concentrations, so they could pose an environmental risk. These substances are widely used in human and animal medicine, so, although only ciprofloxacin is included in the third Watch List, it would be advisable to continue monitoring macrolides in the Basque coast as well.This work was supported by the Basque Water Agency (URA) through the project “Network for monitoring the ecological and chemical status of transitional and coastal waters of the Basque coast”, and partly by the Generalitat de Catalunya (Consolidate Research Group 2017-SGR-14) and the Ministry of Science and Innovation (Project CEX2018-000794-S). The authors acknowledge the help of the entities in charge of the management of the three studied WWTPs (Consorcio de Aguas Bilbao Bizkaia and Aguas del Añarbe), as well as the work of all sampling and laboratory technicians. The anonymous reviewers provided constructive comments to the submitted manuscript. This is contribution number 1113 from the Marine Research of AZTI-BRTA (Basque Research and Technology Alliance).Peer reviewe