PubMed

Related Articles Metabolome-based signature of disease pathology in MS. Mult Scler Relat Disord. 2019 Mar 09;31:12-21 Authors: Andersen SL, Briggs FBS, Winnike JH, Natanzon Y, Maichle S, Knagge KJ, Newby LK, Gregory SG Abstract BACKGROUND: Diagnostic delays are common for multiple sclerosis (MS) since diagnosis typically depends on the presentation of nonspecific clinical symptoms together with radiologically-determined central nervous system (CNS) lesions. It is important to reduce diagnostic delays as earlier initiation of disease modifying therapies mitigates long-term disability. Developing a metabolomic blood-based MS biomarker is attractive, but prior efforts have largely focused on specific subsets of metabolite classes or analytical platforms. Thus, there are opportunities to interrogate metabolite profiles using more expansive and comprehensive approaches for developing MS biomarkers and for advancing our understanding of MS pathogenesis. METHODS: To identify putative blood-based MS biomarkers, we comprehensively interrogated the metabolite profiles in 12 non-Hispanic white, non-smoking, male MS cases who were drug naïve for 3 months prior to biospecimen collection and 13 non-Hispanic white, non-smoking male controls who were frequency matched to cases by age and body mass index. We performed untargeted two-dimensional gas chromatography and time-of-flight mass spectrometry (GCxGC-TOFMS) and targeted lipidomic and amino acid analysis on serum. 325 metabolites met quality control and supervised machine learning was used to identify metabolites most informative for MS status. The discrimination potential of these select metabolites were assessed using receiver operator characteristic curves based on logistic models; top candidate metabolites were defined as having area under the curves (AUC) >80%. The associations between whole-genome expression data and the top candidate metabolites were examined, followed by pathway enrichment analyses. Similar associations were examined for 175 putative MS risk variants and the top candidate metabolites. RESULTS: 12 metabolites were determined to be informative for MS status, of which 6 had AUCs >80%: pyroglutamate, laurate, acylcarnitine C14:1, N-methylmaleimide, and 2 phosphatidylcholines (PC ae 40:5, PC ae 42:5). These metabolites participate in glutathione metabolism, fatty acid metabolism/oxidation, cellular membrane composition, and transient receptor potential channel signaling. Pathway analyses based on the gene expression association for each metabolite suggested enrichment for pathways associated with apoptosis and mitochondrial dysfunction. Interestingly, the predominant MS genetic risk allele HLA-DRB1×15:01 was associated with one of the 6 top metabolites. CONCLUSION: Our analysis represents the most comprehensive description of metabolic changes associated with MS in serum, to date, with the inclusion of genomic and genetic information. We identified atypical metabolic processes that differed between MS patients and controls, which may enable the development of biological targets for diagnosis and treatment. PMID: 30877925 [PubMed - as supplied by publisher]

Related Articles Mitochondria in precision medicine; linking bioenergetics and metabolomics in platelets. Redox Biol. 2019 Mar 10;22:101165 Authors: Chacko BK, Smith MR, Johnson MS, Benavides G, Culp ML, Pilli J, Shiva S, Uppal K, Go YM, Jones DP, Darley-Usmar VM Abstract Mitochondria possess reserve bioenergetic capacity, supporting protection and resilience in the face of disease. Approaches are limited to understand factors that impact mitochondrial functional reserve in humans. We applied the mitochondrial stress test (MST) to platelets from healthy subjects and found correlations between energetic parameters and mitochondrial function. These parameters were not correlated with mitochondrial complex I-IV activities, however, suggesting that other factors affect mitochondrial bioenergetics and metabolism. Platelets from African American patients with sickle cell disease also differed from controls, further showing that other factors impact mitochondrial bioenergetics and metabolism. To test for correlations of platelet metabolites with energetic parameters, we performed an integrated analysis of metabolomics and MST parameters. Subsets of metabolites, including fatty acids and xenobiotics correlated with mitochondrial parameters. The results establish platelets as a platform to integrate bioenergetics and metabolism for analysis of mitochondrial function in precision medicine. PMID: 30877854 [PubMed - as supplied by publisher]

Related Articles Tribute Roland Douce, 1939-2018. Photosynth Res. 2019 Mar 15;: Authors: Joyard J, Lichtenthaler HK Abstract On November 4, 2018, Roland Douce, Professor Emeritus at the University of Grenoble, France, died at the age of 79. In Grenoble, where he spent most of his scientific career, Roland Douce created a world-renowned school of plant science, studying the structure, functions, and interactions of plant organelles involved in photosynthesis, respiration, and photorespiration. His main achievements concern the chemical and functional characterization of chloroplast envelope membranes, the demonstration of the uniqueness of plant mitochondria, and the integration of metabolism within the plant cell, among manifold activities. Roland Douce devoted his whole life to science and research with passion and enthusiasm: he was a true charismatic leader. PMID: 30877517 [PubMed - as supplied by publisher]

Related Articles Recent developments in metabolomics-based research in understanding transgenic grass metabolism. Metabolomics. 2019 Mar 15;15(4):47 Authors: Boonchaisri S, Rochfort S, Stevenson T, Dias DA Abstract BACKGROUND: Transgenic herbicide-resistant (HR) turfgrass together with its associated, broad spectrum herbicides promise cheap, selective and efficient weed control by excluding infested weeds resulting in turf lawn with high uniformity and aesthetic value. The concept of this "weeding program" initiated from modern biotechnology has been widely implemented in several principal crops including maize, soybean, canola and cotton as early as the 1990s. Transgenic HR turfgrass classified as a genetically modified organism (GMO) has undoubtedly caused public concern with respect to its biosafety and legalities similar to well-established HR crops. Nevertheless, applying metabolomics-based approaches which focuses on the identification of the global metabolic state of a biological system in response to either internal or external stimuli can also provide a comprehensive characterization of transgenic grass metabolism and its involvement in biosecurity and public perception. AIM OF REVIEW: This review summaries the recent applications of metabolomics applied to HR crops to predict the molecular and physiological phenotypes of HR turfgrass species, glyphosate-resistant Kentucky bluegrass (Poa pratensis L.) and glufosinate-resistant creeping bentgrass (Agrotis stonifera L.). Additionally, this review also presents background knowledge with respect to the application of metabolomics, transformation of HR crops and its biosafety concerns, turfgrass botanical knowledge and its economic and aesthetic value. KEY SCIENTIFIC CONCEPTS OF REVIEW: The purpose of this review is to demonstrate the molecular and physiological phenotypes of HR turfgrass based on several lines of evidence primarily derived from metabolomics data applied to HR crops to identify alterations on HR turfgrass metabolism as a result of genetic modification that confers resistant traits. PMID: 30877485 [PubMed - in process]

Related Articles Resolving coral photoacclimation dynamics through coupled photophysiological and metabolomic profiling. J Exp Biol. 2019 Mar 15;: Authors: Lohr KE, Camp EF, Kuzhiumparambil U, Lutz A, Leggat W, Patterson JT, Suggett DJ Abstract Corals continuously adjust to short term variation in light availability on shallow reefs. Long-term light alterations can also occur due to natural and anthropogenic stressors, as well as management interventions such as coral transplantation. Although short term photophysiological responses are relatively well-understood in corals, little information is available regarding photoacclimation dynamics over weeks of altered light availability. We coupled photophysiology and metabolomic profiling to explore changes that accompany longer-term photoacclimation in a key Great Barrier Reef coral species (Acropora muricata). High (HL) and low light (LL) acclimated corals were collected from the reef and reciprocally exposed to high and low light ex situ Rapid light curves using Pulse Amplitude Modulation (PAM) fluorometry revealed photophysiological acclimation of LL to HL and HL to LL shifted corals within 21 days. A subset of colonies sampled at 7 and 21 days for untargeted LC-MS and GC-MS metabolomic profiling revealed metabolic reorganization before acclimation was detected using PAM fluorometry. Metabolomic shifts were more pronounced for LL to HL treated corals than their HL to LL counterparts. Compounds driving metabolomic separation between HL-exposed and LL control colonies included amino acids, organic acids, fatty acids and sterols. Reduced glycerol and campesterol suggest decreased translocation of photosynthetic products from symbiont to host in LL to HL shifted corals, with concurrent increases in fatty acid abundance indicating reliance on stored lipids for energy. We discuss how these data provide novel insight into environmental regulation of metabolism and implications for management strategies that drive rapid changes in light availability. PMID: 30877226 [PubMed - as supplied by publisher]

34 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/03/16PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

27 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/03/15PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/03/14PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/03/13PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/03/13PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/03/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/03/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Correction to: Answering biological questions by analysis of the strawberry metabolome. Metabolomics. 2019 Mar 09;15(3):40 Authors: Haugeneder A, Trinkl J, Härtl K, Hoffmann T, Allwood JW, Schwab W Abstract The article Answering biological questions by analysis of the strawberry metabolome, written by Annika Haugeneder, Johanna Trinkl, Katja Härtl, Thomas Hoffman, James William Allwood and Wilfred Schwab, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 26 OCtober, 2018 without open access. After publication in volume 14. Issue 11, Citation Id 145, with the author(s)' decision to opt for Open Choice the copyright of the article changed on 20 December, 2018 to © The Author(s) [Year] and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made. PMID: 30852678 [PubMed - in process]

ColocalizR: An open-source application for cell-based high-throughput colocalization analysis. Comput Biol Med. 2019 Mar 02;107:227-234 Authors: Sauvat A, Leduc M, Müller K, Kepp O, Kroemer G Abstract The microscopic assessment of the colocalization of fluorescent signals has been widely used in cell biology. Although imaging techniques have drastically improved over the past decades, the quantification of colocalization by measures such as the Pearson correlation coefficient or Manders overlap coefficient, has not changed. Here, we report the development of an R-based application that allows to (i) automatically segment cells and subcellular compartments, (ii) measure morphology and texture features, and (iii) calculate the degree of colocalization within each cell. Colocalization can thus be studied on a cell-by-cell basis, permitting to perform statistical analyses of cellular populations and subpopulations. ColocalizR has been designed to parallelize tasks, making it applicable to the analysis of large data sets. Its graphical user interface makes it suitable for researchers without specific knowledge in image analysis. Moreover, results can be exported into a wide range of formats rendering post-analysis adaptable to statistical requirements. This application and its source code are freely available at https://github.com/kroemerlab/ColocalizR. PMID: 30852249 [PubMed - as supplied by publisher]

Resveratrol and other dietary polyphenols are inhibitors of estrogen metabolism in human breast cancer cells. J Steroid Biochem Mol Biol. 2019 Mar 06;: Authors: Poschner S, Maier-Salamon A, Thalhammer T, Jäger W Abstract Polyphenols in foods and dietary supplements are commonly used for the prevention and treatment of a variety of malignancies, including breast cancer. However, daily intake by patients with breast cancer is controversial, as these compounds may stimulate cancer growth. Estrogens serve key roles in breast cancer cell proliferation; therefore, understanding the interaction between endogenous steroid hormones and natural dietary polyphenols is essential. Currently, comprehensive knowledge regarding these effects remains limited. The current review summarizes the dose-dependent in vitro and in vivo interactions of resveratrol and other dietary polyphenols with estrogen precursors, active estrogens, catechol estrogens and their respective glucuronidated, sulfated, glutathionated or O-methylated metabolites in estrogen receptor alpha negative (ERα-) and positive (ERα+) breast cancer. Which estrogen-metabolizing enzymes are affected by polyphenols is also reviewed in detail. Furthermore, the impacts of dose and therapy duration on disease development and progression in patients with breast cancer are discussed. The present article is part of a Special Issue titled 'CSR 2018'. PMID: 30851384 [PubMed - as supplied by publisher]

Interoperable and scalable data analysis with microservices: Applications in Metabolomics. Bioinformatics. 2019 Mar 09;: Authors: Emami Khoonsari P, Moreno P, Bergmann S, Burman J, Capuccini M, Carone M, Cascante M, de Atauri P, Foguet C, Gonzalez-Beltran A, Hankemeier T, Haug K, He S, Herman S, Johnson D, Kale N, Larsson A, Neumann S, Peters K, Pireddu L, Rocca-Serra P, Roger P, Rueedi R, Ruttkies C, Sadawi N, Salek RM, Sansone SA, Schober D, Selivanov V, Thévenot EA, van Vliet M, Zanetti G, Steinbeck C, Kultima K, Spjuth O Abstract MOTIVATION: Developing a robust and performant data analysis workflow that integrates all necessary components whilst still being able to scale over multiple compute nodes is a challenging task. We introduce a generic method based on the microservice architecture, where software tools are encapsulated as Docker containers that can be connected into scientific workflows and executed using the Kubernetes container orchestrator. RESULTS: We developed a virtual research environment which facilitates rapid integration of new tools and developing scalable and interoperable workflows for performing metabolomics data analysis. The environment can be launched on-demand on cloud resources and desktop computers. IT-expertise requirements on the user side are kept to a minimum, and workflows can be re-used effortlessly by any novice user. We validate our method in the field of metabolomics on two mass spectrometry, one nuclear magnetic resonance spectroscopy and one fluxomics study. We showed that the method scales dynamically with increasing availability of computational resources. We demonstrated that the method facilitates interoperability using integration of the major software suites resulting in a turn-key workflow encompassing all steps for mass-spectrometry-based metabolomics including preprocessing, statistics, and identification. Microservices is a generic methodology that can serve any scientific discipline and opens up for new types of large-scale integrative science. AVAILABILITY AND IMPLEMENTATION: The PhenoMeNal consortium maintains a web portal (https://portal.phenomenal-h2020.eu) providing a GUI for launching the virtual research environment. The GitHub repository https://github.com/phnmnl/ hosts the source code of all projects. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID: 30851093 [PubMed - as supplied by publisher]

Related Articles Discovery of novel carbohydrate-active enzymes through the rational exploration of the protein sequences space. Proc Natl Acad Sci U S A. 2019 Mar 08;: Authors: Helbert W, Poulet L, Drouillard S, Mathieu S, Loiodice M, Couturier M, Lombard V, Terrapon N, Turchetto J, Vincentelli R, Henrissat B Abstract Over the last two decades, the number of gene/protein sequences gleaned from sequencing projects of individual genomes and environmental DNA has grown exponentially. Only a tiny fraction of these predicted proteins has been experimentally characterized, and the function of most proteins remains hypothetical or only predicted based on sequence similarity. Despite the development of postgenomic methods, such as transcriptomics, proteomics, and metabolomics, the assignment of function to protein sequences remains one of the main challenges in modern biology. As in all classes of proteins, the growing number of predicted carbohydrate-active enzymes (CAZymes) has not been accompanied by a systematic and accurate attribution of function. Taking advantage of the CAZy database, which groups CAZymes into families and subfamilies based on amino acid similarities, we recombinantly produced 564 proteins selected from subfamilies without any biochemically characterized representatives, from distant relatives of characterized enzymes and from nonclassified proteins that show little similarity with known CAZymes. Screening these proteins for activity on a wide collection of carbohydrate substrates led to the discovery of 13 CAZyme families (two of which were also discovered by others during the course of our work), revealed three previously unknown substrate specificities, and assigned a function to 25 subfamilies. PMID: 30850540 [PubMed - as supplied by publisher]

Related Articles Virulence factors produced by Staphylococcus aureus biofilms have a moonlighting function contributing to biofilm integrity. Mol Cell Proteomics. 2019 Mar 08;: Authors: Graf AC, Leonard A, Schäuble M, Rieckmann LM, Hoyer J, Maaß S, Lalk M, Becher D, Pané-Farré J, Riedel K Abstract Staphylococcus aureus is the causative agent of various biofilm-associated infections in humans causing major healthcare problems worldwide. This type of infection is inherently difficult to treat due to a reduced metabolic activity of biofilm-embedded cells and the protective nature of a surrounding extracellular matrix (ECM). However, little is known about S. aureus biofilm physiology and in particular the proteinaceous composition of the ECM. Thus, we cultivated S. aureus biofilms in a flow system and comprehensively profiled intracellular and extracellular (ECM and flow-through (FT)) biofilm proteomes, as well as the extracellular metabolome in comparison to planktonic cultures. Our analyses revealed the expression of many pathogenicity factors within S. aureus biofilms as indicated by a high abundance of capsule biosynthesis proteins along with various secreted virulence factors, including hemolysins, leukotoxins, and lipases as a part of the ECM. The activity of ECM virulence factors was confirmed in a hemolysis assay and a Galleria mellonella pathogenicity model. In addition, we uncovered a so far unacknowledged moonlighting function of secreted virulence factors and ribosomal proteins trapped in the ECM: namely their contribution to biofilm integrity. Mechanistically, it was revealed that this stabilizing effect is mediated by the strong positive charge of alkaline virulence factors and ribosomal proteins in an acidic ECM environment, which is caused by the release of fermentation products like formate, lactate, and acetate as a consequence of oxygen limitation in biofilms. The strong positive charge of these proteins most likely mediates electrostatic interactions with anionic cell surface components, eDNA, and anionic metabolites. In consequence, this leads to strong cell aggregation and biofilm stabilization. Collectively, our study identified a new molecular mechanism during S. aureus biofilm formation and thus significantly widens the understanding of biofilm-associated S. aureus infections - an essential prerequisite for the development of novel antimicrobial therapies. PMID: 30850421 [PubMed - as supplied by publisher]

29 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/03/09PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/03/08PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.