| 1. |
- Harlacher, Eva, et al.
(författare)
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Increased levels of a mycophenolic acid metabolite in patients with kidney failure negatively affect cardiomyocyte health.
- 2024
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Ingår i: Frontiers in cardiovascular medicine. - 2297-055X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) significantly increases cardiovascular risk and mortality, and the accumulation of uremic toxins in the circulation upon kidney failure contributes to this increased risk. We thus performed a screening for potential novel mediators of reduced cardiovascular health starting from dialysate obtained after hemodialysis of patients with CKD. The dialysate was gradually fractionated to increased purity using orthogonal chromatography steps, with each fraction screened for a potential negative impact on the metabolic activity of cardiomyocytes using a high-throughput MTT-assay, until ultimately a highly purified fraction with strong effects on cardiomyocyte health was retained. Mass spectrometry and nuclear magnetic resonance identified the metabolite mycophenolic acid-β-glucuronide (MPA-G) as a responsible substance. MPA-G is the main metabolite from the immunosuppressive agent MPA that is supplied in the form of mycophenolate mofetil (MMF) to patients in preparation for and after transplantation or for treatment of autoimmune and non-transplant kidney diseases. The adverse effect of MPA-G on cardiomyocytes was confirmed in vitro, reducing the overall metabolic activity and cellular respiration while increasing mitochondrial reactive oxygen species production in cardiomyocytes at concentrations detected in MMF-treated patients with failing kidney function. This study draws attention to the potential adverse effects of long-term high MMF dosing, specifically in patients with severely reduced kidney function already displaying a highly increased cardiovascular risk.
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| 2. |
- Andersson, Anna, et al.
(författare)
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Molecular changes among non-volatile disinfection by-products between drinking water treatment and consumer taps
- 2021
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Ingår i: Environmental Science. - : Royal Society of Chemistry. - 2053-1400 .- 2053-1419. ; 7:12, s. 2335-2345
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Tidskriftsartikel (refereegranskat)abstract
- The formation of disinfection by-products (DBPs) during drinking water treatment has been associated with various health concerns but the total DBP exposure is still unknown. In this study, molecular level non-target analysis by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was used to study non-volatile DBPs, and how their composition changes during water distribution in four drinking water treatment plants (DWTPs) in Sweden using different types of raw water and disinfection processes. The largest portion of tap water DBP compositions were detected also at the DWTPs, highlighting that these DBP formulae were rather stable and contribute to human DBP exposure. Yet the number of detected DBPs decreased 14-48% between drinking water treatment and consumer taps in the three plants in which no mixing of water from other DWTPs in the distribution system occurred showing active DBP processing in the water distribution network. While considerable amounts of bromine-containing DBPs were detected upon chemical disinfection in some DWTPs, few of them were detected in the tap water samples, likely due to debromination by hydrolytic reactions. The overall fewer non-volatile DBPs detected in tap waters, along with changed distribution among chlorine and bromine DBPs, demonstrate that DBP mixtures are highly dynamic and that DBP measurements at DWTPs do not adequately reflect exposure at the point-of-use. Clearly, more knowledge about changes of DBP mixtures through the distribution system is needed to improve DBP exposure assessments.
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| 3. |
- Andersson, Anna, et al.
(författare)
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Selective removal of natural organic matter during drinking water production changes the composition of disinfection by-products
- 2020
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Ingår i: Environmental Science. - : ROYAL SOC CHEMISTRY. - 2053-1400 .- 2053-1419. ; 6:3, s. 779-794
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Tidskriftsartikel (refereegranskat)abstract
- Disinfection by-products (DBPs) are potentially toxic compounds formed upon chemical disinfection of drinking water. Controlling the levels and characteristics of dissolved organic matter (DOM) as precursor material for DBPs is a major target to reduce DBP formation. A pilot-scale treatment including suspended ion exchange (SIX (R)), a ceramic microfilter (CeraMac (R)) with in-line coagulation and optional pre-ozonation followed by granular activated carbon (GAC) filtration was compared with a conventional full-scale treatment based on DOM removal and DBP formation using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), rapid fractionation, liquid chromatography organic carbon detection (LC-OCD), adsorbable organic halogens (AOX) and trihalomethane (THM) analysis. The new treatment combination showed different selectivity for DOM removal, compared to the conventional, leading to changes in composition of the DBPs formed. SIX (R) and GAC had the largest impacts on reducing AOX and THM formation potentials but the high adsorptive capacity of GAC affected the diversity of detected DBPs most. Chlorination and chloramination of pilot treated water with doses normally used in Sweden produced low levels of AOX compared to the full-scale treatment, but FT-ICR MS revealed an abundance of brominated DBP species in contrast with the conventional treatment, which were dominated by chlorinated DBPs. This finding was largely linked to the high DOM removal by the pilot treatment, causing an increased Br-/C ratio and a higher formation of HOBr. Potential increases in Br-DBPs are important to consider in minimizing health risks associated with DBPs, because of the supposed higher toxicity of Br-DBPs compared to Cl-DBPs.
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| 4. |
- Andersson, Anna, et al.
(författare)
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Waterworks-specific composition of drinking water disinfection by-products
- 2019
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Ingår i: Environmental Science. - Cambridge : Royal Society of Chemistry. - 2053-1400 .- 2053-1419. ; :5, s. 861-872
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Tidskriftsartikel (refereegranskat)abstract
- Reactions between chemical disinfectants and natural organic matter (NOM) upon drinking water treatment result in formation of potentially harmful disinfection by-products (DBPs). The diversity of DBPs formed is high and a large portion remains unknown. Previous studies have shown that non-volatile DBPs are important, as much of the total toxicity from DBPs has been related to this fraction. To further understand the composition and variation of DBPs associated with this fraction, non-target analysis with ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was employed to detect DBPs at four Swedish waterworks using different types of raw water and treatments. Samples were collected five times covering a full year. A common group of DBPs formed at all four waterworks was detected, suggesting a similar pool of DBP precursors in all raw waters that might be related to phenolic moieties. However, the largest proportion (64–92%) of the assigned chlorinated and brominated molecular formulae were unique, i.e. were solely found in one of the four waterworks. In contrast, the compositional variations of NOM in the raw waters and samples collected prior to chemical disinfection were rather limited.This indicated that waterworks-specific DBPs presumably originated from matrix effects at the point of disinfection, primarily explained by differences in bromide levels, disinfectants (chlorine versus chloramine) and different relative abundances of isomers among the NOM compositions studied. The large variation of observed DBPs in the toxicologically relevant non-volatile fraction indicates that non-targeted monitoring strategies might be valuable to ensure relevant DBP monitoring in the future.
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| 5. |
- Fernández-Remolar, David C., et al.
(författare)
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Productivity contribution of Paleozoic woodlands to the formation of shale hosted massive sulfide deposits in the Iberian Pyrite Belt (Tharsis, Spain)
- 2018
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Ingår i: Journal of Geophysical Research - Biogeosciences. - : John Wiley & Sons. - 2169-8953 .- 2169-8961. ; 123:3, s. 1017-1040
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Tidskriftsartikel (refereegranskat)abstract
- The geological materials produced during catastrophic and destructive events are an essential source of paleobiological knowledge. The paleobiological information recorded by such events can be rich in information on the size, diversity, and structure of paleocommunities. In this regard, the geobiological study of late Devonian organic matter sampled in Tharsis (Iberian Pyrite Belt) provided some new insights into a Paleozoic woodland community,which was recorded as massive sulfides and black shale deposits affected by a catastrophic event. Sample analysis using TOF-SIMS (Time of Flight Secondary Ion Mass Spectrometer), and complemented by GC/MS (Gas Chromatrograph/Mass Spectrometer) identified organic compounds showing a very distinct distribution in the rock. While phytochemical compounds occur homogeneously in the sample matrix that is composed of black shale, the microbial-derived organics are more abundant in the sulfide nodules. The co-occurrence of sulfur bacteria compounds and the overwhelming presence of phytochemicals provide support for the hypothesis that the formation of the massive sulfides resulted from a high rate of vegetal debris production and its oxidation through sulfate reduction under suboxic to anoxic conditions. A continuous supply of iron from hydrothermal activity coupled with microbial activity was strictly necessary to produce this massive orebody. A rough estimate of the woodland biomass was made possible by accounting for the microbial sulfur production activity recorded in the metallic sulfide. As a result, the biomass size of the late Devonian woodland community was comparable to modern woodlands like the Amazon or Congo rainforests.
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| 6. |
- Fernández-Remolar, David C., et al.
(författare)
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Unveiling microbial preservation under hyperacidic and oxidizing conditions in the Oligocene Rio Tinto deposit
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The preservation of biosignatures on Mars is largely associated with extensive deposits of clays formed under mild early Noachian conditions (> 3.9 Ga). They were followed by widespread precipitation of acidic sulfates considered adverse for biomolecule preservation. In this paper, an exhaustive mass spectrometry investigation of ferric subsurface materials in the Rio Tinto gossan deposit (~ 25 Ma) provides evidence of well-preserved molecular biosignatures under oxidative and acidic conditions. Time of flight secondary ion mass spectrometry (ToF–SIMS) analysis shows a direct association between physical-templating biological structures and molecular biosignatures. This relation implies that the quality of molecular preservation is exceptional and provides information on microbial life formerly operating in the shallow regions of the Rio Tinto subsurface. Consequently, low-pH oxidative environments on Mars could also record molecular information about ancient life in the same way as the Noachian clay-rich deposits.
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| 7. |
- Gonsior, Michael, et al.
(författare)
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Changes in Dissolved Organic Matter during the Treatment Processes of a Drinking Water Plant in Sweden and Formation of Previously Unknown Disinfection Byproducts
- 2014
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Ingår i: Environmental Science and Technology. - : American Chemical Society. - 0013-936X .- 1520-5851. ; 48:21, s. 12714-12722
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Tidskriftsartikel (refereegranskat)abstract
- The changes in dissolved organic matter (DOM) throughout the treatment processes in a drinking water treatment plant in Sweden and the formation of disinfection byproducts (DBPs) were evaluated by using ultra-high-resolution mass spectrometry (resolution of similar to 500000 at m/z 400) and nuclear magnetic resonance (NMR). Mass spectrometric results revealed that flocculation induced substantial changes in the DOM and caused quantitative removal of DOM constituents that usually are associated with DBP formation While half of the chromophoric DOM (CDOM) was removed by flocculation, similar to 4-5 mg L-1 total organic carbon remained in the finished water. A conservative approach revealed the formation of similar to 800 mass spectrometry ions with unambiguous molecular formula assignments that contained at least one halogen atom. These molecules likely represented new DBPs, which could not be prevented by the flocculation process. The most abundant m/z peaks, associated with formed DBPs, could be assigned to C5HO3Cl3, C5HO3Cl2Br, C5HO3ClBr2 using isotope simulation patterns. Other halogen-containing formulas suggested the presence of halogenated polyphenolic and aromatic acid-type structures, which was supported by possible structures that matched the lower molecular mass range (maximum of 10 carbon atoms) of these DBPs. H-1 NMR before and after disinfection revealed an similar to 2% change in the overall H-1 NMR signals supporting a significant change in the DOM caused by disinfection. This study underlines the fact that a large and increasing number of people are exposed to a very diverse pool of organohalogens through water by both drinking and uptake through the skin upon contact. Nontarget analytical approaches are indispensable for revealing the magnitude of this exposure and to test alternative ways to reduce it.
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| 8. |
- Gonsior, Michael, et al.
(författare)
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Chemodiversity of dissolved organic matter in the Amazon Basin
- 2016
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Ingår i: Biogeosciences. - : COPERNICUS GESELLSCHAFT MBH. - 1726-4170 .- 1726-4189. ; 13:14, s. 4279-4290
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Tidskriftsartikel (refereegranskat)abstract
- Regions in the Amazon Basin have been associated with specific biogeochemical processes, but a detailed chemical classification of the abundant and ubiquitous dissolved organic matter (DOM), beyond specific indicator compounds and bulk measurements, has not yet been established. We sampled water from different locations in the Negro, Madeira/Jamari and Tapajos River areas to characterize the molecular DOM composition and distribution. Ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) combined with excitation emission matrix (EEM) fluorescence spectroscopy and parallel factor analysis (PARAFAC) revealed a large proportion of ubiquitous DOM but also unique area-specific molecular signatures. Unique to the DOM of the Rio Negro area was the large abundance of high molecular weight, diverse hydrogen-deficient and highly oxidized molecular ions deviating from known lignin or tannin compositions, indicating substantial oxidative processing of these ultimately plant-derived polyphenols indicative of these black waters. In contrast, unique signatures in the Madeira/Jamari area were defined by presumably labile sulfur-and nitrogen-containing molecules in this white water river system. Waters from the Tapajos main stem did not show any substantial unique molecular signatures relative to those present in the Rio Madeira and Rio Negro, which implied a lower organic molecular complexity in this clear water tributary, even after mixing with the main stem of the Amazon River. Beside ubiquitous DOM at average H / C and O / C elemental ratios, a distinct and significant unique DOM pool prevailed in the black, white and clear water areas that were also highly correlated with EEM-PARAFAC components and define the frameworks for primary production and other aspects of aquatic life.
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| 9. |
- Gonsior, Michael, et al.
(författare)
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Molecular characterization of effluent organic matter identified by ultrahigh resolution mass spectrometry
- 2011
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Ingår i: WATER RESEARCH. - : Elsevier Science B.V., Amsterdam.. - 0043-1354. ; 45:9, s. 2943-2953
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Tidskriftsartikel (refereegranskat)abstract
- Effluent dissolved organic matter (EfOM) collected from the secondary-treated wastewater of the Orange County Sanitation District (OCSD) located in Fountain Valley, California, USA was compared to natural organic matter collected from the Suwannee River (SRNOM), Florida using ultrahigh resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Furthermore, the two different treatment processes at OCSD, activated sludge and trickling filter, were separately investigated. The blend of these two effluents was further evaluated after it had passed through the microfiltration process of the Advanced Water Purification Facility (AWPF) at Orange County Water District (OCWD). EfOM contained 872 different m/z peaks that were unambiguously assigned to exact molecular formulae containing a single sulfur atom and carbon, hydrogen and oxygen atoms (CHOS formulae). In contrast, the SRNOM sample only contained 152 CHOS formulae. The trend in CHO molecular compositions was opposite with 2500 CHO formulae assigned for SRNOM but only about 1000 for EfOM. The CHOS-derived mass peaks with highest abundances in EfOM could be attributed to surfactants such as linear alkyl benzene sulfonates (LAS), their co-products dialkyl tetralin sulfonates (DATS) and their biodegraded metabolites such as sulfophenyl carboxylic acids (SPC). The differences between the treatments were found minor with greater differences between sampling dates than treatment methods used. (C) 2011 Elsevier Ltd. All rights reserved.
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| 10. |
- Jansson, Janet, et al.
(författare)
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Metabolomics reveals metabolic biomarkers of Crohn's disease
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:7, s. e6386-
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Tidskriftsartikel (refereegranskat)abstract
- The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.
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