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  1. Article ; Online: Direct Analysis of Marine Dissolved Organic Matter Using LC-FT-ICR MS.

    Lechtenfeld, Oliver J / Kaesler, Jan / Jennings, Elaine K / Koch, Boris P

    Environmental science & technology

    2024  Volume 58, Issue 10, Page(s) 4637–4647

    Abstract: Marine dissolved organic matter (DOM) is an important component of the global carbon cycle, yet its intricate composition and the sea salt matrix pose major challenges for chemical analysis. We introduce a direct injection, reversed-phase liquid ... ...

    Abstract Marine dissolved organic matter (DOM) is an important component of the global carbon cycle, yet its intricate composition and the sea salt matrix pose major challenges for chemical analysis. We introduce a direct injection, reversed-phase liquid chromatography ultrahigh resolution mass spectrometry approach to analyze marine DOM without the need for solid-phase extraction. Effective separation of salt and DOM is achieved with a large chromatographic column and an extended isocratic aqueous step. Postcolumn dilution of the sample flow with buffer-free solvents and implementing a counter gradient reduced salt buildup in the ion source and resulted in excellent repeatability. With this method, over 5,500 unique molecular formulas were detected from just 5.5 nmol carbon in 100 μL of filtered Arctic Ocean seawater. We observed a highly linear detector response for variable sample carbon concentrations and a high robustness against the salt matrix. Compared to solid-phase extracted DOM, our direct injection method demonstrated superior sensitivity for heteroatom-containing DOM. The direct analysis of seawater offers fast and simple sample preparation and avoids fractionation introduced by extraction. The method facilitates studies in environments, where only minimal sample volume is available e.g. in marine sediment pore water, ice cores, or permafrost soil solution. The small volume requirement also supports higher spatial (e.g., in soils) or temporal sample resolution (e.g., in culture experiments). Chromatographic separation adds further chemical information to molecular formulas, enhancing our understanding of marine biogeochemistry, chemodiversity, and ecological processes.
    MeSH term(s) Dissolved Organic Matter ; Mass Spectrometry/methods ; Water/chemistry ; Fresh Water/chemistry ; Sodium Chloride ; Carbon
    Chemical Substances Dissolved Organic Matter ; Water (059QF0KO0R) ; Sodium Chloride (451W47IQ8X) ; Carbon (7440-44-0)
    Language English
    Publishing date 2024-03-01
    Publishing country United States
    Document type Journal Article
    ISSN 1520-5851
    ISSN (online) 1520-5851
    DOI 10.1021/acs.est.3c07219
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Post column infusion of an internal standard into LC-FT-ICR MS enables semi-quantitative comparison of dissolved organic matter in original samples.

    Rodrigues Matos, Rebecca / Jennings, Elaine K / Kaesler, Jan / Reemtsma, Thorsten / Koch, Boris P / Lechtenfeld, Oliver J

    The Analyst

    2024  

    Abstract: Ultrahigh resolution mass spectrometry hyphenated with liquid chromatography (LC) is an emerging tool to explore the isomeric composition of dissolved organic matter (DOM). However, matrix effects limit the potential for semi-quantitative comparison of ... ...

    Abstract Ultrahigh resolution mass spectrometry hyphenated with liquid chromatography (LC) is an emerging tool to explore the isomeric composition of dissolved organic matter (DOM). However, matrix effects limit the potential for semi-quantitative comparison of DOM molecule abundances across samples. We introduce a post-column infused internal standard (PCI-IS) for reversed-phase LC-FT-ICR MS measurements of DOM and systematically evaluate matrix effects, detector linearity and the precision of mass peak intensities. Matrix effects for model compounds spiked into freshwater DOM samples ranging from a headwater stream to a major river were reduced by 5-10% for PCI-IS corrected mass peak intensities as compared to raw (
    Language English
    Publishing date 2024-05-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 210747-8
    ISSN 1364-5528 ; 0003-2654
    ISSN (online) 1364-5528
    ISSN 0003-2654
    DOI 10.1039/d4an00119b
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: How aromatic dissolved organic matter differs in competitiveness against organic micropollutant adsorption.

    Wang, Qi / Lechtenfeld, Oliver J / Rietveld, Luuk C / Schuster, Jonas / Ernst, Mathias / Hofman-Caris, Roberta / Kaesler, Jan / Wang, Chunmiao / Yang, Min / Yu, Jianwei / Zietzschmann, Frederik

    Environmental science and ecotechnology

    2024  Volume 21, Page(s) 100392

    Abstract: Activated carbon is employed for the adsorption of organic micropollutants (OMPs) from water, typically present in concentrations ranging from ng ... ...

    Abstract Activated carbon is employed for the adsorption of organic micropollutants (OMPs) from water, typically present in concentrations ranging from ng L
    Language English
    Publishing date 2024-01-27
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2666-4984
    ISSN (online) 2666-4984
    DOI 10.1016/j.ese.2024.100392
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Correction to Absorption Mode Spectral Processing Improves Data Quality of Natural Organic Matter Analysis by Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry.

    Da Silva, Maria P / Kaesler, Jan M / Reemtsma, Thorsten / Lechtenfeld, Oliver J

    Journal of the American Society for Mass Spectrometry

    2021  Volume 32, Issue 9, Page(s) 2495

    Language English
    Publishing date 2021-08-19
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 1073671-2
    ISSN 1879-1123 ; 1044-0305
    ISSN (online) 1879-1123
    ISSN 1044-0305
    DOI 10.1021/jasms.1c00236
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Absorption Mode Spectral Processing Improves Data Quality of Natural Organic Matter Analysis by Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry.

    Da Silva, Maria P / Kaesler, Jan M / Reemtsma, Thorsten / Lechtenfeld, Oliver J

    Journal of the American Society for Mass Spectrometry

    2020  Volume 31, Issue 7, Page(s) 1615–1618

    Abstract: Natural organic matter (NOM) plays an important role in elemental cycles and ecology. Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) is an ultrahigh resolution technique used to molecularly resolve the complexity of NOM mixtures. ...

    Abstract Natural organic matter (NOM) plays an important role in elemental cycles and ecology. Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) is an ultrahigh resolution technique used to molecularly resolve the complexity of NOM mixtures. However, even the very high mass resolution of FT-ICR-MS may result in multiple formula assignments to peaks in an NOM spectrum, especially at the high mass-to-charge ratio (
    Language English
    Publishing date 2020-06-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1073671-2
    ISSN 1879-1123 ; 1044-0305
    ISSN (online) 1879-1123
    ISSN 1044-0305
    DOI 10.1021/jasms.0c00138
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Online Counter Gradient LC-FT-ICR-MS Enables Detection of Highly Polar Natural Organic Matter Fractions.

    Han, Limei / Kaesler, Jan / Peng, Chang / Reemtsma, Thorsten / Lechtenfeld, Oliver J

    Analytical chemistry

    2020  Volume 93, Issue 3, Page(s) 1740–1748

    Abstract: Natural organic matter (NOM) is a highly complex mixture of natural organic molecules. The recent developments in NOM molecular characterization methods have shown that ESI-FT-ICR hyphenated with liquid chromatography (LC) is a promising approach to also ...

    Abstract Natural organic matter (NOM) is a highly complex mixture of natural organic molecules. The recent developments in NOM molecular characterization methods have shown that ESI-FT-ICR hyphenated with liquid chromatography (LC) is a promising approach to also obtain chemical information (such as polarity and molecular size) about NOM molecules. However, due to changing solvent composition during gradient elution in LC-FT-ICR-MS, ionization conditions also change throughout the chromatographic separation process. In this study, we applied a post-LC column counter gradient (CG) to ensure stable solvent conditions for transient ESI-MS signals. Suwanee River Fulvic Acid (SRFA) standard and a peat pore water were used as representative dissolved NOM samples for method development and validation. Our results show that in polar NOM fractions (which elute with <50% methanol) the TIC intensity and number of assigned molecular formulas were increased by 48% and 20%, as compared to the standard gradient (SG) method. Further application of a Q-isolation and selective ion accumulation for low abundance fractions revealed over 3 times more molecular formulas (especially for CHNO, CHOS, CHNOS formula classes) than in full scan mode. The number of detected highly polar NOM compounds (with elemental ratios H/C < 1, O/C > 0.6) were more than 20 times larger for CG-LC mode as compared to direct infusion (DI) (5715 vs 266 MF). We conclude that the application of a postcolumn counter gradient in LC-FT-ICR-MS analyses of NOM offers novel insight into the most polar fractions of NOM which are inaccessible in conventional DI measurements.
    Language English
    Publishing date 2020-12-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1508-8
    ISSN 1520-6882 ; 0003-2700
    ISSN (online) 1520-6882
    ISSN 0003-2700
    DOI 10.1021/acs.analchem.0c04426
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  7. Article: Multi-Class Cancer Subtyping in Salivary Gland Carcinomas with MALDI Imaging and Deep Learning.

    Pertzborn, David / Arolt, Christoph / Ernst, Günther / Lechtenfeld, Oliver J / Kaesler, Jan / Pelzel, Daniela / Guntinas-Lichius, Orlando / von Eggeling, Ferdinand / Hoffmann, Franziska

    Cancers

    2022  Volume 14, Issue 17

    Abstract: Salivary gland carcinomas (SGC) are a heterogeneous group of tumors. The prognosis varies strongly according to its type, and even the distinction between benign and malign tumor is challenging. Adenoid cystic carcinoma (AdCy) is one subgroup of SGCs ... ...

    Abstract Salivary gland carcinomas (SGC) are a heterogeneous group of tumors. The prognosis varies strongly according to its type, and even the distinction between benign and malign tumor is challenging. Adenoid cystic carcinoma (AdCy) is one subgroup of SGCs that is prone to late metastasis. This makes accurate tumor subtyping an important task. Matrix-assisted laser desorption/ionization (MALDI) imaging is a label-free technique capable of providing spatially resolved information about the abundance of biomolecules according to their mass-to-charge ratio. We analyzed tissue micro arrays (TMAs) of 25 patients (including six different SGC subtypes and a healthy control group of six patients) with high mass resolution MALDI imaging using a 12-Tesla magnetic resonance mass spectrometer. The high mass resolution allowed us to accurately detect single masses, with strong contributions to each class prediction. To address the added complexity created by the high mass resolution and multiple classes, we propose a deep-learning model. We showed that our deep-learning model provides a per-class classification accuracy of greater than 80% with little preprocessing. Based on this classification, we employed methods of explainable artificial intelligence (AI) to gain further insights into the spectrometric features of AdCys.
    Language English
    Publishing date 2022-09-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14174342
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  8. Article ; Online: ROS Induction Targets Persister Cancer Cells with Low Metabolic Activity in NRAS-Mutated Melanoma.

    Eichhoff, Ossia M / Stoffel, Corinne I / Käsler, Jan / Briker, Luzia / Turko, Patrick / Karsai, Gergely / Zila, Nina / Paulitschke, Verena / Cheng, Phil F / Leitner, Alexander / Bileck, Andrea / Zamboni, Nicola / Irmisch, Anja / Balazs, Zsolt / Tastanova, Aizhan / Pascoal, Susana / Johansen, Pål / Wegmann, Rebekka / Mena, Julien /
    Othman, Alaa / Viswanathan, Vasanthi S / Wenzina, Judith / Aloia, Andrea / Saltari, Annalisa / Dzung, Andreas / Krauthammer, Michael / Schreiber, Stuart L / Hornemann, Thorsten / Distel, Martin / Snijder, Berend / Dummer, Reinhard / Levesque, Mitchell P

    Cancer research

    2023  Volume 83, Issue 7, Page(s) 1128–1146

    Abstract: Clinical management of melanomas with NRAS mutations is challenging. Targeting MAPK signaling is only beneficial to a small subset of patients due to resistance that arises through genetic, transcriptional, and metabolic adaptation. Identification of ... ...

    Abstract Clinical management of melanomas with NRAS mutations is challenging. Targeting MAPK signaling is only beneficial to a small subset of patients due to resistance that arises through genetic, transcriptional, and metabolic adaptation. Identification of targetable vulnerabilities in NRAS-mutated melanoma could help improve patient treatment. Here, we used multiomics analyses to reveal that NRAS-mutated melanoma cells adopt a mesenchymal phenotype with a quiescent metabolic program to resist cellular stress induced by MEK inhibition. The metabolic alterations elevated baseline reactive oxygen species (ROS) levels, leading these cells to become highly sensitive to ROS induction. In vivo xenograft experiments and single-cell RNA sequencing demonstrated that intratumor heterogeneity necessitates the combination of a ROS inducer and a MEK inhibitor to inhibit both tumor growth and metastasis. Ex vivo pharmacoscopy of 62 human metastatic melanomas confirmed that MEK inhibitor-resistant tumors significantly benefited from the combination therapy. Finally, oxidative stress response and translational suppression corresponded with ROS-inducer sensitivity in 486 cancer cell lines, independent of cancer type. These findings link transcriptional plasticity to a metabolic phenotype that can be inhibited by ROS inducers in melanoma and other cancers.
    Significance: Metabolic reprogramming in drug-resistant NRAS-mutated melanoma cells confers sensitivity to ROS induction, which suppresses tumor growth and metastasis in combination with MAPK pathway inhibitors.
    MeSH term(s) Humans ; Reactive Oxygen Species ; Proto-Oncogene Proteins B-raf/genetics ; Melanoma/drug therapy ; Melanoma/genetics ; Melanoma/pathology ; Skin Neoplasms/drug therapy ; Protein Kinase Inhibitors/therapeutic use ; Mitogen-Activated Protein Kinase Kinases/genetics ; Cell Line, Tumor ; Mutation ; Membrane Proteins/genetics ; GTP Phosphohydrolases/genetics
    Chemical Substances Reactive Oxygen Species ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Protein Kinase Inhibitors ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; NRAS protein, human (EC 3.6.1.-) ; Membrane Proteins ; GTP Phosphohydrolases (EC 3.6.1.-)
    Language English
    Publishing date 2023-03-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-22-1826
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  9. Article ; Online: Topology and structure of an engineered human cohesin complex bound to Pds5B.

    Hons, Michael T / Huis In 't Veld, Pim J / Kaesler, Jan / Rombaut, Pascaline / Schleiffer, Alexander / Herzog, Franz / Stark, Holger / Peters, Jan-Michael

    Nature communications

    2016  Volume 7, Page(s) 12523

    Abstract: The cohesin subunits Smc1, Smc3 and Scc1 form large tripartite rings which mediate sister chromatid cohesion and chromatin structure. These are thought to entrap DNA with the help of the associated proteins SA1/2 and Pds5A/B. Structural information is ... ...

    Abstract The cohesin subunits Smc1, Smc3 and Scc1 form large tripartite rings which mediate sister chromatid cohesion and chromatin structure. These are thought to entrap DNA with the help of the associated proteins SA1/2 and Pds5A/B. Structural information is available for parts of cohesin, but analyses of entire cohesin complexes are limited by their flexibility. Here we generated a more rigid 'bonsai' cohesin by truncating the coiled coils of Smc1 and Smc3 and used single-particle electron microscopy, chemical crosslinking-mass spectrometry and in silico modelling to generate three-dimensional models of cohesin bound to Pds5B. The HEAT-repeat protein Pds5B forms a curved structure around the nucleotide-binding domains of Smc1 and Smc3 and bridges the Smc3-Scc1 and SA1-Scc1 interfaces. These results indicate that Pds5B forms an integral part of the cohesin ring by contacting all other cohesin subunits, a property that may reflect the complex role of Pds5 proteins in controlling cohesin-DNA interactions.
    MeSH term(s) Cell Cycle Proteins/chemistry ; Cell Cycle Proteins/metabolism ; Cell Cycle Proteins/ultrastructure ; Chromosomal Proteins, Non-Histone/chemistry ; Chromosomal Proteins, Non-Histone/metabolism ; Chromosomal Proteins, Non-Histone/ultrastructure ; Computer Simulation ; DNA-Binding Proteins/metabolism ; Humans ; Models, Molecular ; Multiprotein Complexes/metabolism ; Protein Binding ; Protein Domains ; Protein Engineering ; Transcription Factors/metabolism ; Cohesins
    Chemical Substances Cell Cycle Proteins ; Chromosomal Proteins, Non-Histone ; DNA-Binding Proteins ; Multiprotein Complexes ; PDS5B protein, human ; Transcription Factors
    Language English
    Publishing date 2016-08-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/ncomms12523
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  10. Article ; Online: Identification, characterization, and structure analysis of the cyclic di-AMP-binding PII-like signal transduction protein DarA.

    Gundlach, Jan / Dickmanns, Achim / Schröder-Tittmann, Kathrin / Neumann, Piotr / Kaesler, Jan / Kampf, Jan / Herzberg, Christina / Hammer, Elke / Schwede, Frank / Kaever, Volkhard / Tittmann, Kai / Stülke, Jörg / Ficner, Ralf

    The Journal of biological chemistry

    2014  Volume 290, Issue 5, Page(s) 3069–3080

    Abstract: The cyclic dimeric AMP nucleotide c-di-AMP is an essential second messenger in Bacillus subtilis. We have identified the protein DarA as one of the prominent c-di-AMP receptors in B. subtilis. Crystal structure analysis shows that DarA is highly ... ...

    Abstract The cyclic dimeric AMP nucleotide c-di-AMP is an essential second messenger in Bacillus subtilis. We have identified the protein DarA as one of the prominent c-di-AMP receptors in B. subtilis. Crystal structure analysis shows that DarA is highly homologous to PII signal transducer proteins. In contrast to PII proteins, the functionally important B- and T-loops are swapped with respect to their size. DarA is a homotrimer that binds three molecules of c-di-AMP, each in a pocket located between two subunits. We demonstrate that DarA is capable to bind c-di-AMP and with lower affinity cyclic GMP-AMP (3'3'-cGAMP) but not c-di-GMP or 2'3'-cGAMP. Consistently the crystal structure shows that within the ligand-binding pocket only one adenine is highly specifically recognized, whereas the pocket for the other adenine appears to be promiscuous. Comparison with a homologous ligand-free DarA structure reveals that c-di-AMP binding is accompanied by conformational changes of both the fold and the position of the B-loop in DarA.
    MeSH term(s) Bacillus subtilis/metabolism ; Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Crystallography, X-Ray ; Dinucleoside Phosphates/metabolism ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Signal Transduction
    Chemical Substances Bacterial Proteins ; Dinucleoside Phosphates ; cyclic diadenosine phosphate
    Language English
    Publishing date 2014-11-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M114.619619
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