Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis:3. Untargeted metabolomics

Intramammary infection leading to bovine mastitis is the leading disease problem affecting dairy cows and has marked effects on the milk produced by infected udder quarters. An experimental model of Streptococcus uberis mastitis has previously been investigated for clinical, immunological and pathophysiological alteration in milk, and has been the subject of peptidomic and quantitative proteomic investigation. The same sample set has now been investigated with a metabolomics approach using liquid chromatography and mass spectrometry. The analysis revealed over 3000 chromatographic peaks, of which 690 were putatively annotated with a metabolite. Hierarchical clustering analysis and principal component analysis demonstrated that metabolite changes due to S. uberis infection were maximal at 81 hours post challenge with metabolites in the milk from the resolution phase at 312 hours post challenge being closest to the pre-challenge samples. Metabolic pathway analysis revealed that the majority of the metabolites mapped to carbohydrate and nucleotide metabolism show a decreasing trend in concentration up to 81 hours post-challenge whereas an increasing trend was found in lipid metabolites and di-, tri- and tetra-peptides up to the same time point. The increase in these peptides coincides with an increase in larger peptides found in the previous peptidomic analysis and is likely to be due to protease degradation of milk proteins. Components of bile acid metabolism, linked to the FXR pathway regulating inflammation, were also increased. Metabolomic analysis of the response in milk during mastitis provides an essential component to the full understanding of the mammary gland’s response to infection

The NORMAN Suspect List Exchange (NORMAN-SLE): facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry

Background: The NORMAN Association (https://www.norman-.network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-.network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for "suspect screening" lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https:// zenodo.org/communities/norman-.sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA's CompTox Chemicals Dashboard (https://comptox. epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101).Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the "one substance, one assessment" approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-.network.com/nds/SLE/)

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

The NORMAN Suspect List Exchange (NORMAN-SLE): Facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry

Background: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for “suspect screening” lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide. Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA’s CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101). Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the “one substance, one assessment” approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/)

The NORMAN Suspect List Exchange (NORMAN-SLE): facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry

The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for "suspect screening" lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.The NORMAN-SLE project has received funding from the NORMAN Association via its joint proposal of activities. HMT and ELS are supported by the Luxembourg National Research Fund (FNR) for project A18/BM/12341006. ELS, PC, SEH, HPHA, ZW acknowledge funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101036756, project ZeroPM: Zero pollution of persistent, mobile substances. The work of EEB, TC, QL, BAS, PAT, and JZ was supported by the National Center for Biotechnology Information of the National Library of Medicine (NLM), National Institutes of Health (NIH). JOB is the recipient of an NHMRC Emerging Leadership Fellowship (EL1 2009209). KVT and JOB acknowledge the support of the Australian Research Council (DP190102476). The Queensland Alliance for Environmental Health Sciences, The University of Queensland, gratefully acknowledges the financial support of the Queensland Department of Health. NR is supported by a Miguel Servet contract (CP19/00060) from the Instituto de Salud Carlos III, co-financed by the European Union through Fondo Europeo de Desarrollo Regional (FEDER). MM and TR gratefully acknowledge financial support by the German Ministry for Education and Research (BMBF, Bonn) through the project “Persistente mobile organische Chemikalien in der aquatischen Umwelt (PROTECT)” (FKz: 02WRS1495 A/B/E). LiB acknowledges funding through a Research Foundation Flanders (FWO) fellowship (11G1821N). JAP and JMcL acknowledge financial support from the NIH for CCSCompendium (S50 CCSCOMPEND) via grants NIH NIGMS R01GM092218 and NIH NCI 1R03CA222452-01, as well as the Vanderbilt Chemical Biology Interface training program (5T32GM065086-16), plus use of resources of the Center for Innovative Technology (CIT) at Vanderbilt University. TJ was (partly) supported by the Dutch Research Council (NWO), project number 15747. UFZ (TS, MaK, WB) received funding from SOLUTIONS project (European Union’s Seventh Framework Programme for research, technological development and demonstration under Grant Agreement No. 603437). TS, MaK, WB, JPA, RCHV, JJV, JeM and MHL acknowledge HBM4EU (European Union’s Horizon 2020 research and innovation programme under the grant agreement no. 733032). TS acknowledges funding from NFDI4Chem—Chemistry Consortium in the NFDI (supported by the DFG under project number 441958208). TS, MaK, WB and EMLJ acknowledge NaToxAq (European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant Agreement No. 722493). S36 and S63 (HPHA, SEH, MN, IS) were funded by the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) Project No. (FKZ) 3716 67 416 0, updates to S36 (HPHA, SEH, MN, IS) by the German Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) Project No. (FKZ) 3719 65 408 0. MiK acknowledges financial support from the EU Cohesion Funds within the project Monitoring and assessment of water body status (No. 310011A366 Phase III). The work related to S60 and S82 was funded by the Swiss Federal Office for the Environment (FOEN), KK and JH acknowledge the input of Kathrin Fenner’s group (Eawag) in compiling transformation products from European pesticides registration dossiers. DSW and YDF were supported by the Canadian Institutes of Health Research and Genome Canada. The work related to S49, S48 and S77 was funded by the MAVA foundation; for S77 also the Valery Foundation (KG, JaM, BG). DML acknowledges National Science Foundation Grant RUI-1306074. YL acknowledges the National Natural Science Foundation of China (Grant No. 22193051 and 21906177), and the Chinese Postdoctoral Science Foundation (Grant No. 2019M650863). WLC acknowledges research project 108C002871 supported by the Environmental Protection Administration, Executive Yuan, R.O.C. Taiwan (Taiwan EPA). JG acknowledges funding from the Swiss Federal Office for the Environment. AJW was funded by the U.S. Environmental Protection Agency. LuB, AC and FH acknowledge the financial support of the Generalitat Valenciana (Research Group of Excellence, Prometeo 2019/040). KN (S89) acknowledges the PhD fellowship through Marie Skłodowska-Curie grant agreement No. 859891 (MSCA-ETN). Exposome-Explorer (S34) was funded by the European Commission projects EXPOsOMICS FP7-KBBE-2012 [308610]; NutriTech FP7-KBBE-2011-5 [289511]; Joint Programming Initiative FOODBALL 2014–17. CP acknowledges grant RYC2020-028901-I funded by MCIN/AEI/1.0.13039/501100011033 and “ESF investing in your future”, and August T Larsson Guest Researcher Programme from the Swedish University of Agricultural Sciences. The work of ML, MaSe, SG, TL and WS creating and filling the STOFF-IDENT database (S2) mostly sponsored by the German Federal Ministry of Education and Research within the RiSKWa program (funding codes 02WRS1273 and 02WRS1354). XT acknowledges The National Food Institute, Technical University of Denmark. MaSch acknowledges funding by the RECETOX research infrastructure (the Czech Ministry of Education, Youth and Sports, LM2018121), the CETOCOEN PLUS project (CZ.02.1.01/0.0/0.0/15_003/0000469), and the CETOCOEN EXCELLENCE Teaming 2 project supported by the Czech ministry of Education, Youth and Sports (No CZ.02.1.01/0.0/0.0/17_043/0009632).Peer reviewe