PubMed

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.

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 2019/03/07PubMed 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.

20 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 2019/03/06PubMed 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.

162 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 2019/03/05PubMed 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.

Related Articles Metabolomics profiling and pathway analysis of human plasma and urine reveal further insights into the multifactorial nature of Coronary Artery Disease (CAD). Clin Chim Acta. 2019 Feb 28;: Authors: Amin AM, Mostafa H, Arif NH, Kader MASKA, Hay YK Abstract BACKGROUND: Coronary artery disease (CAD) claims lives yearly. Nuclear magnetic resonance (1H NMR) metabolomics analysis is efficient in identifying metabolic biomarkers which lend credence to diagnosis. We identified CAD metabotypes and its implicated pathways using 1H NMR analysis. METHODS: We analysed plasma and urine samples of 50 stable CAD patients and 50 healthy controls using 1H NMR. Orthogonal partial least square discriminant analysis (OPLS-DA) followed by multivariate logistic regression (MVLR) models were developed to indicate the discriminating metabotypes. RESULTS: Both plasma and urine OPLS-DA models had specificity, sensitivity and accuracy of 100%, 96% and 98%, respectively. Plasma MVLR model had specificity, sensitivity, accuracy and AUROC of 92%, 86%, 89% and 0.96, respectively. The MVLR model of urine had specificity, sensitivity, accuracy and AUROC of 90%, 80%, 85% and 0.92, respectively. 35 and 12 metabolites were identified in plasma and urine metabotypes, respectively. Metabolic pathway analysis revealed that urea cycle, aminoacyl-tRNA biosynthesis and synthesis and degradation of ketone bodies pathways were significantly disturbed in plasma, while methylhistidine metabolism and galactose metabolism pathways were significantly disturbed in urine. The enrichment over representation analysis against SNPs-associated-metabolite sets library revealed that 85 SNPs were significantly enriched in plasma metabotype. CONCLUSIONS: Cardiometabolic diseases, dysbiotic gut-microbiota and genetic variabilities are largely implicated in the pathogenesis of CAD. PMID: 30826371 [PubMed - as supplied by publisher]

Related Articles Environmental cadmium exposure induces alterations in the urinary metabolic profile of pregnant women. Int J Hyg Environ Health. 2019 Feb 27;: Authors: Li H, Huang K, Jin S, Peng Y, Liu W, Wang M, Zhang H, Zhang B, Xia W, Li Y, Lu S, Xu S Abstract Cadmium (Cd) is a well-recognized, hazardous toxic heavy metal, and the adverse effects of high-level Cd exposure on human health have been well documented. However, little is known about the health effects of low-level environmental Cd exposure on pregnant women. The objective of this study was to assess urinary metabolic alterations in pregnant women exposed to environmental Cd, and to identify informative biomarkers. Urine samples from 246 pregnant women in the first trimester of pregnancy were collected, and urinary Cd concentrations were quantified using inductively coupled plasma mass spectrometry (ICP-MS). Urinary metabolomics was analyzed by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Cd-related metabolic biomarkers were examined by comparing the samples of the first and third tertiles of Cd exposure classifications, using a partial least-squares discriminant (PLS-DA) model. Five putative biomarkers were identified, including L-cystine, L-tyrosine, dityrosine, histamine, and uric acid, all of which were related to oxidative stress and nephrotoxic effects induced by Cd exposure. The results show that low-level environmental Cd exposure could induce metabolite profile alterations in pregnant women, which might be associated with adverse health effects. Our findings provide new insights into the early molecular events following Cd exposure, and may be valuable for the health risk assessment of Cd exposure during pregnancy. PMID: 30826206 [PubMed - as supplied by publisher]

Metabolomics driven analysis of 11 Portulaca leaf taxa as analysed via UPLC-ESI-MS/MS and chemometrics. Phytochemistry. 2019 Feb 27;161:117-129 Authors: Farag MA, Shakour ZTA Abstract Portulaca oleracea, commonly known as purslane, is a popular plant of considerable value for its nutritive composition as well as traditional medicinal uses. P. oleracea is reported to possess neuroprotective, antimicrobial, antidiabetic, antioxidant, anti-inflammatory, antiulcerogenic, and anticancer activities. Three taxa of P. oleracea L. (P. oleracea, P. rausii and P. granulatostellulata) are grown as mixed populations in several locations in Egypt. The close morphological similarities among these taxa warrants development of methods for their correct identification or classification. We aimed in this study to assess metabolome differences among three P. oleracea taxa via ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) in the context of their genetic diversity and/or geographical origin. A total of 85 metabolites were identified including 6 amino acids, 22 phenolic compounds, 16 alkaloids, and 11 fatty acids characterized based on their MSn and UV spectra. Methoxylated flavone glycosides, O-flavonoids, C-flavonoids and four previously undescribed cyclodopa alkaloids are reported in P. oleracea for the first time. Multivariate data analyses were used for samples classification and revealing that cyclodopa alkaloids (oleracein A, C, K and N) contributed the most for accessions classification. To the best of our knowledge, this study presents the first metabolite profile of Portulaca and its compositional differences that provide chemical based evidence for its nutritive and/or health benefits. PMID: 30825706 [PubMed - as supplied by publisher]

Related Articles The role of neurotransmitters and neuromodulators in the pathogenesis of cluster headache: a review. Neurol Sci. 2019 Mar 02;: Authors: D'Andrea G, Gucciardi A, Perini F, Leon A Abstract The pathogenesis underlying cluster headache remains an unresolved issue. Although both the autonomic system and the hypothalamus play a central role, the modality of their involvement remains largely unknown. It is, also, unknown why the duration of the pain attacks is so brief and why their onset and termination are abrupt and extremely painful. This review summarizes the evidence to date accumulated in favor of a possible role of anomalies in the metabolism of tyrosine, tryptophan, and arginine in these unresolved issues. PMID: 30825019 [PubMed - as supplied by publisher]

Related Articles Time-resolved decoding of metabolic signatures of in vitro growth of the hemibiotrophic pathogen Colletotrichum sublineolum. Sci Rep. 2019 Mar 01;9(1):3290 Authors: Tugizimana F, Djami-Tchatchou AT, Fahrmann JF, Steenkamp PA, Piater LA, Dubery IA Abstract Metabolomics has emerged as a powerful approach to comprehensively interrogate cellular biochemistry. As such, we applied an untargeted liquid chromatography-mass spectrometry metabolomic strategy to elucidate metabolome changes in the anthracnose-causing hemibiotrophic sorghum pathogen, Colletotrichum sublineolum. An in vitro batch culture study model with different carbon sources, glucose, arabinose and rhamnose, were used to support fungal growth over a period of twelve days. Metabolites representing the intracellular and extracellular (secreted) metabolomes were extracted with methanol and subjected to LC-MS analyses. Chemometric modelling revealed a metabolic variation trajectory, comprising three distinct stages that metabolically describe the adaptation of the fungus to diminishing nutrients. Selected marker gene expression indicated stage one (0-3 d.p.i) as corresponding to the early logarithmic phase. Stage two can be interpreted as an intermediate transitionary stage with stage three corresponding to the stationary phase (9-12 d.p.i). Stage one was characterised by up-regulation of endo-metabolites such as ferricrocin, fatty acids and flavone-conjugates, while stage three was characterised by the secretion of phytotoxins, including colletotrichin and colletotric acid. Ultimately, results from our in vitro model reveal previously unknown insights into the dynamic aspects of metabolome reprogramming in the growth phases of Colletotrichum spp as determined by nutrients obtainable from plant cell walls. PMID: 30824820 [PubMed - in process]

Related Articles Luigi Maiuri: un Grande Uomo - a Great Spirit. Cell Death Dis. 2019 Mar 01;10(3):209 Authors: Piacentini M, Kroemer G Abstract PMID: 30824687 [PubMed - in process]

Related Articles Twenty Years on: Metabolomics in Helminth Research. Trends Parasitol. 2019 Feb 26;: Authors: Kokova D, Mayboroda OA Abstract This contribution makes a critical assessment of the metabolomics application to helminthic infection research. To ensure a cross-comparison of the results published by different laboratories over a period of almost two decades, we restrict the discussion to only the publications where nuclear magnetic resonance (NMR) spectroscopy is used as the analytical platform. We review the metabolites consistently reported for the body fluids of animals infected with the parasitic helminths and the characteristic metabolic patterns, arguing that the field needs a complete integration of metabolomics into research lines that examine host-helminth interactions. PMID: 30824203 [PubMed - as supplied by publisher]

Related Articles Transcriptomic and metabolomic analysis of ZmYUC1 mutant reveals the role of auxin during early endosperm formation in maize. Plant Sci. 2019 Apr;281:133-145 Authors: Bernardi J, Battaglia R, Bagnaresi P, Lucini L, Marocco A Abstract Kernel size in cereal is an important agronomic trait controlled by the interaction of genetic and environmental factors. The endosperm occupies most of the kernel area; for this reason, the endosperm cells dimension, number and metabolic content strongly influence kernel properties. This paper presents the transcriptomic and metabolomic analysis of the maize defective endosperm 18 (de18) mutant, where auxin accumulation in the endosperm is impaired. This mutation, involving the ZmYuc1 gene, leads to a reduced kernel size compared to the wild-type line B37. Our results mainly indicate that IAA concentration controls sugar and protein metabolism during kernel differentiation and it is necessary for BETL formation. Furthermore, a fine tuning of different auxin conjugates is reported as the main mechanism to counteract the auxin deficit. Some candidates as master regulators of endosperm transcriptional regulation mediated by auxin are found between MYB and MADS-box gene families. A link between auxin and storage protein accumulation is highlighted, suggesting that IAA directly or indirectly, through CK or ABA, regulates the transcription of zein coding genes. This study represents a move forward with respect to the current knowledge about the role of auxin during maize endosperm differentiation thus revealing the genes that are modulated by auxin and that control agronomic traits as kernel size and metabolic composition. PMID: 30824046 [PubMed - in process]

Related Articles Metabolomics analysis of a mouse model for chronic exposure to ambient PM2.5. Environ Pollut. 2019 Apr;247:953-963 Authors: Xu Y, Wang W, Zhou J, Chen M, Huang X, Zhu Y, Xie X, Li W, Zhang Y, Kan H, Ying Z Abstract Chronic ambient fine particulate matter (PM2.5) exposure correlates with various adverse health outcomes. Its impact on the circulating metabolome-a comprehensive functional readout of the interaction between an organism's genome and environment-has not however been fully understood. This study thus performed metabolomics analyses using a chronic PM2.5 exposure mouse model. C57Bl/6J mice (female) were subjected to inhalational concentrated ambient PM2.5 (CAP) or filtered air (FA) exposure for 10 months. Their sera were then analyzed by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). These analyses identified 2570 metabolites in total, and 148 of them were significantly different between FA- and CAP-exposed mice. The orthogonal partial least-squares discriminant analysis (OPLS-DA) and heatmap analyses displayed evident clustering of FA- and CAP-exposed samples. Pathway analyses identified 6 perturbed metabolic pathways related to amino acid metabolism. In contrast, biological characterization revealed that 71 differential metabolites were related to lipid metabolism. Furthermore, our results showed that CAP exposure increased stress hormone metabolites, 18-oxocortisol and 5a-tetrahydrocortisol, and altered the levels of circadian rhythm biomarkers including melatonin, retinal and 5-methoxytryptophol. PMID: 30823350 [PubMed - in process]

Adropin treatment restores cardiac glucose oxidation in pre-diabetic obese mice. J Mol Cell Cardiol. 2019 Feb 26;: Authors: Thapa D, Xie B, Zhang M, Stoner MW, Manning JR, Huckestein BR, Edmunds LR, Mullett SJ, McTiernan CF, Wendell SG, Jurczak MJ, Scott I Abstract Exposure to a high fat (HF) diet promotes increased fatty acid uptake, fatty acid oxidation and lipid accumulation in the heart. These maladaptive changes impact cellular energy metabolism and may promote the development of cardiac dysfunction. Attempts to increase cardiac glucose utilization have been proposed as a way to reverse cardiomyopathy in obese and diabetic individuals. Adropin is a nutrient-regulated metabolic hormone shown to promote glucose oxidation over fatty acid oxidation in skeletal muscle homogenates in vitro. The focus of the current study was to investigate whether adropin can regulate substrate metabolism in the heart following prolonged exposure to a HF diet in vivo. Mice on a long-term HF diet received serial intraperitoneal injections of vehicle or adropin over three days. Cardiac glucose oxidation was significantly reduced in HF animals, which was rescued by acute adropin treatment. Significant decreases in cardiac pyruvate dehydrogenase activity were observed in HF animals, which were also reversed by adropin treatment. In contrast to previous studies, this change was unrelated to Pdk4 expression, which remained elevated in both vehicle- and adropin-treated HF mice. Instead, we show that adropin modulated the expression of the mitochondrial acetyltransferase enzyme GCN5L1, which altered the acetylation status and activity of fuel metabolism enzymes to favor glucose utilization. Our findings indicate that adropin exposure leads to increased cardiac glucose oxidation under HF conditions, and may provide a future therapeutic avenue in the treatment of diabetic cardiomyopathy. PMID: 30822408 [PubMed - as supplied by publisher]

Assessment of NAD+metabolism in human cell cultures, erythrocytes, cerebrospinal fluid and primate skeletal muscle. Anal Biochem. 2019 Feb 26;: Authors: Demarest TG, Truong GTD, Lovett J, Mohanty JG, Mattison JA, Mattson MP, Ferrucci L, Bohr VA, Moaddel R Abstract The reduction-oxidation state of NAD+/NADH is critical for cellular health with NAD+ and its metabolites playing critical roles in aging and pathologies. Given the inherent autooxidation of reduced dinucleotides (i.e. NADH/NADPH), and the well-established differential stability, the accurate measurement of NAD+ and its metabolites is technically challenging. Moreover, sample processing, normalization and measurement strategies can profoundly alter results. Here we developed a rapid and sensitive liquid chromatography mass spectrometry-based method to quantify the NAD+ metabolome with careful consideration of these intrinsic chemical instabilities. Utilizing this method we assess NAD+ metabolite stabilities and determine the presence and concentrations of NAD+ metabolites in clinically relevant human samples including cerebrospinal fluid, erythrocytes, and primate skeletal muscle. PMID: 30822397 [PubMed - as supplied by publisher]

Serum metabolomics analysis of the effect of exercise on nonalcoholic fatty liver disease. Endocr Connect. 2019 Mar 01;: Authors: Li J, Zhao Y, Huang C, Chen Z, Shi X, Li L, Chen Z, Li X Abstract OBJECTIVE: Exercise benefits people with nonalcoholic fatty liver disease (NAFLD). The aim of this study was to identify a panel of biomarkers and to provide the possible mechanism for the effect of exercise on NAFLD patients via an untargeted mass spectrometry-based serum metabolomics study. METHODS: NAFLD patients were classified randomly into a control group (n=74) and a 6-month vigorous exercise (n=68) group. Differences in serum metabolic profiles were analyzed using untargeted ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technology. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to validate differences between these two groups, and altered metabolites were obtained by ANOVA (fold change<2, P<0.05) and identified with the online database Metlin and an in-house database. RESULTS: Metabolic profiling and multiple statistical analyses of the serum samples indicated significant differences between the NAFLD patients in the control and the 6-month vigorous exercise groups. Finally, 36 metabolites were identified between the control vs exercise groups. These metabolites were mainly associated with glycerophospholipid- and sphingolipid-related pathways. CONCLUSION: Our study demonstrates that glycerophospholipid and sphingolipid alterations may contribute to the mechanism underlying the effect of exercise on NAFLD patients. A LC-MS-based metabolomics approach has potential value for screening exercise-induced biomarkers. PMID: 30822271 [PubMed - as supplied by publisher]

Related Articles Impact of primary carbon sources on microbiome shaping and biotransformation of pharmaceuticals and personal care products. Biodegradation. 2019 Feb 28;: Authors: Rossmassler K, Kim S, Broeckling CD, Galloway S, Prenni J, De Long SK Abstract Knowledge of the conditions that promote the growth and activity of pharmaceutical and personal care product (PPCP)-degrading microorganisms within mixed microbial systems are needed to shape microbiomes in biotreatment reactors and manage process performance. Available carbon sources influence microbial community structure, and specific carbon sources could potentially be added to end-of-treatment train biotreatment systems (e.g., soil aquifer treatment [SAT]) to select for the growth and activity of a range of microbial phylotypes that collectively degrade target PPCPs. Herein, the impacts of primary carbon sources on PPCP biodegradation and microbial community structure were explored to identify promising carbon sources for PPCP biotreatment application. Six types of primary carbon sources were investigated: casamino acids, two humic acid and peptone mixtures (high and low amounts of humic acid), molasses, an organic acids mixture, and phenol. Biodegradation was tracked for five PPCPs (diclofenac, 5-fluorouracil, gemfibrozil, ibuprofen, and triclosan). Primary carbon sources were found to differentially impact microbial community structures and rates and efficiencies of PPCP biotransformation. Of the primary carbon sources tested, casamino acids, organic acids, and phenol showed the fastest biotransformation; however, on a biomass-normalized basis, both humic acid-peptone mixtures showed comparable or superior biotransformation. By comparing microbial communities for the different primary carbon sources, abundances of unclassified Beijerinckiaceae, Beijerinckia, Sphingomonas, unclassified Sphingomonadaceae, Flavobacterium, unclassified Rhizobiales, and Nevskia were statistically linked with biotransformation of specific PPCPs. PMID: 30820709 [PubMed - as supplied by publisher]