PubMed

Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischemic heart? Cardiovasc Res. 2017 Apr 29;: Authors: Perrino C, Barabási AL, Condorelli G, Davidson SM, De Windt L, Dimmeler S, Engel FB, Hausenloy DJ, Hill JA, Van Laake LW, Lecour S, Leor J, Madonna R, Mayr M, Prunier F, Sluijter JP, Schulz R, Thum T, Ytrehus K, Ferdinandy P Abstract Despite advances in myocardial reperfusion therapies, acute myocardial ischemia/reperfusion injury and consequent ischemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signaling networks activated in the ischemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets. High-throughput techniques allow high-resolution, genome-wide investigation of genetic variants, epigenetic modifications and associated gene expression profiles. Platforms such as proteomics and metabolomics (not described here in detail) also offer simultaneous readouts of hundreds of proteins and metabolites. Isolated omics analyses usually provide Big Data requiring large data storage, advanced computational resources and complex bioinformatics tools. The possibility of integrating different omics approaches gives new hope to better understand the molecular circuitry activated by myocardial ischemia, putting it in the context of the human "diseasome".Since modifications of cardiac gene expression have been consistently linked to pathophysiology of the ischemic heart, the integration of epigenomic and transcriptomic data seems a promising approach to identify crucial disease networks. Thus, the scope of this Position Paper will be to highlight potentials and limitations of these approaches, and to provide recommendations to optimize the search for novel diagnostic or therapeutic targets for acute ischemia/reperfusion injury and ischemic heart failure in the post-genomic era. PMID: 28460026 [PubMed - as supplied by publisher]

Related Articles Metabolomics reveals intratumor heterogeneity - Implications for precision medicine. EBioMedicine. 2017 Apr 24;: Authors: Liu X, Locasale JW PMID: 28457617 [PubMed - as supplied by publisher]

Related Articles Changes in hepatic TRβ protein expression, lipogenic gene expression, and long chain acylcarnitine levels during chronic hyperthyroidism and T3 withdrawal in a mouse model. Thyroid. 2017 Apr 29;: Authors: Ohba K, Sinha RA, Leow MK, Iannucci LF, Singh BK, Zhou J, Kovalik JP, Liao XH, Refetoff S, Sng JCG, Yen PM Abstract BACKGROUND: Thyroid hormone (TH) has important roles in regulating hepatic metabolism. We previously reported that most hepatic genes activated by a single T3 injection became desensitized after multiple injections, and that approximately 10% of target genes did not return to basal expression levels after T3 withdrawal despite normalization of serum TH and TSH levels. To determine the possible mechanism(s) for desensitization and incomplete recovery of hepatic target gene transcription and their effects on metabolism, we measured mRNA and/or protein expression levels of key regulators of TH action as well as metabolomic changes after chronic T3 treatment and withdrawal. METHODS: Adult male mice were treated with daily injections of T3 (20 μg per100 g body weight) for 14 days followed by the cessation of T3 for 10 days. Livers were harvested at 6 hours, 24 hours, and 14 days after the first T3 injection, and 10 days after withdrawal, and then analyzed by qRT-PCR, Western blotting, and metabolomics. RESULTS: Although TH receptor (TRα and TRβ) mRNAs decreased slightly after chronic T3 treatment, only TRβ protein decreased before returning to basal expression level after withdrawal. Expression of other regulators of TH action was unchanged. TRβ protein expression also was decreased in adult male monocarboxylate transporter-8 (Mct8)-knockout mice, an in vivo model of chronic intrahepatic hyperthyroidism. Previously, we found increased hepatic long-chain acylcarnitines (LCACs) after acute TH treatment; however, in this study, LCACs were unchanged after chronic T3, and paradoxically increased after T3 withdrawal. Pathway analyses of our previous microarray results showed up-regulation of lipogenic genes after acute T3 treatment and withdrawal. Phosphorylation of acetyl-CoA carboxylase also decreased after T3 withdrawal. CONCLUSIONS: Decreased hepatic TRβ protein expression occurred after chronic T3 exposure in adult male wild-type and Mct8-knockout mice. Gene array pathway and metabolomics analyses showed abnormalities in hepatic lipogenic gene expression and acylcarnitine levels, respectively, after withdrawal despite normalization of serum TSH and TH levels. These findings may help explain the variable clinical presentations of some patients during hyperthyroidism and recovery, since TRβ protein, target gene expression, and metabolic adaptive changes can occur in individual tissues without necessarily being reflected by circulating TH and TSH concentrations. PMID: 28457184 [PubMed - as supplied by publisher]

Related Articles Ionomic and physiological responses to low nitrogen stress in Tibetan wild and cultivated barley. Plant Physiol Biochem. 2017 Feb;111:257-265 Authors: Quan X, Zeng J, Han Z, Zhang G Abstract In a previous study, we identified the low-nitrogen (LN) tolerant accessions from the Tibetan wild barley (Hordeum vulgare subsp. spontaneum). In this study, two wild barley genotypes (XZ149, LN-tolerant and XZ56, LN-sensitive) and a barley cultivar ZD9 (H. vulgare) were used to determine the LN tolerant mechanism underlying the wild barley in the ionomic and physiological aspects. XZ149 exhibited higher LN tolerance with highest relative dry weight and N accumulation among three barley genotypes under LN stress. When exposed to LN stress, XZ149 had more N transportation from roots to leaves, and remained relatively higher activities of nitrate reductase (NR, EC.1.7.1.1) and glutamine synthetase (GS, EC.6.3.1.2) in leaves than other two genotypes, ensuring its higher capacity of N assimilation and utilization. The ionome analysis showed that LN stress had a significant effect on tissue ionome and the effect was genotypic and tissue-specific difference. On the whole, XZ149 maintained more stable Mn and Cu contents in roots, and less reduction of root P, K and Ca contents than XZ56 and ZD9 when exposed to LN stress. It may be assumed that more N movement into shoots, greater N assimilating capacity and specific rearrangement of nutrient element levels in tissues under LN stress are attributed to LN tolerance in XZ149. PMID: 27951495 [PubMed - indexed for MEDLINE]

Related Articles Experimental Evolution of Metabolic Dependency in Bacteria. PLoS Genet. 2016 Nov;12(11):e1006364 Authors: D'Souza G, Kost C Abstract Bacteria frequently lose biosynthetic genes, thus making them dependent on an environmental uptake of the corresponding metabolite. Despite the ubiquity of this 'genome streamlining', it is generally unclear whether the concomitant loss of biosynthetic functions is favored by natural selection or rather caused by random genetic drift. Here we demonstrate experimentally that a loss of metabolic functions is strongly selected for when the corresponding metabolites can be derived from the environment. Serially propagating replicate populations of the bacterium Escherichia coli in amino acid-containing environments revealed that auxotrophic genotypes rapidly evolved in less than 2,000 generations in almost all replicate populations. Moreover, auxotrophs also evolved in environments lacking amino acids-yet to a much lesser extent. Loss of these biosynthetic functions was due to mutations in both structural and regulatory genes. In competition experiments performed in the presence of amino acids, auxotrophic mutants gained a significant fitness advantage over the evolutionary ancestor, suggesting their emergence was selectively favored. Interestingly, auxotrophic mutants derived amino acids not only via an environmental uptake, but also by cross-feeding from coexisting strains. Our results show that adaptive fitness benefits can favor biosynthetic loss-of-function mutants and drive the establishment of intricate metabolic interactions within microbial communities. PMID: 27814362 [PubMed - indexed for MEDLINE]

Related Articles Functional and cellular consequences of covalent target protein modification by furan in rat liver. Toxicology. 2016 Jun 15;361-362:49-61 Authors: Ramm S, Limbeck E, Mally A Abstract Furan hepatotoxicity is thought to be linked to covalent binding of its reactive metabolite, cis-2-butene-1,4-dial, to hepatic proteins critical for cell homeostasis and survival. We previously identified 61 putative furan target proteins, which participate in various cellular processes including carbohydrate metabolism, fatty acid β-oxidation, adenosine triphosphate (ATP) synthesis, protein folding and maintenance of redox homeostasis. To further investigate the biological significance of target protein modification, this study was designed to determine the impact of furan on the activity of key target enzymes involved in glycolysis, β-oxidation, ATP synthesis, and redox regulation in rat liver, and to link these functional changes to alterations in cellular processes. While cis-2-butene-1,4-dial inhibited thioredoxin 1 (Txn1) in a cell-free assay, in livers of rats treated with a single high dose of furan Txn1 activity was markedly increased due to rapid up-regulation of Txn1 mRNA expression. Significant inhibition of glyceraldehyde-3-phosphate dehydrogenase and metabolic changes consistent with blocked glycolytic breakdown of glucose were observed in rat liver in response to a single high dose of furan. In contrast, furan treatment resulted in increased activity of enoyl-CoA hydratase and enhanced production of ketone bodies, indicative of increased utilization of fatty acids as energy source. Consistent with changes in TCA cycle metabolites, furan treatment resulted in a reduction of succinate dehydrogenase activity, supporting mitochondrial dysfunction as a critical event in furan toxicity. No significant changes in target protein function were observed following repeated administration of furan at lower dose (0.1 and 0.5mg/kg bw for 4 weeks) closer to estimated human exposure to furan via food. Although the relative contribution of furan mediated alterations in metabolic pathways and antioxidant defense to the overall toxic response to furan, including considerations of dose and time, remains to be established, our work contributes to mapping biological processes and toxicity pathways modulated by reactive electrophiles. PMID: 27402187 [PubMed - indexed for MEDLINE]

Patchouli alcohol ameliorates dextran sodium sulfate-induced experimental colitis and suppresses tryptophan catabolism. Pharmacol Res. 2017 Apr 26;: Authors: Qu C, Yuan ZW, Yu XT, Huang YF, Yang GH, Chen JN, Lai XP, Su ZR, Zeng HF, Xie Y, Zhang XJ Abstract Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C15H26O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days. The mice were then given PA (10, 20 and 40mg/kg) or sulfasalazine (SASP, 200mg/kg) as positive control via oral administration for 7 days. At the end of study, animals were sacrificed and samples were collected for pathological and other analysis. In addition, a metabolite profiling and a targeted metabolite analysis, based on the Ultra-Performance Liquid Chromatography coupled with mass spectrometry (UPLC-MS) approach, were performed to characterize the metabolic changes in plasma. The results revealed that PA significantly reduced the disease activity index (DAI) and ameliorated the colonic injury of DSS mice. The levels of colonic MPO and cytokines involving TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10 also declined. Furthermore, PA improved the intestinal epithelial barrier by enhancing the level of colonic expression of the tight junction (TJ) proteins, for instance ZO-1, ZO-2, claudin-1 and occludin, and by elevating the levels of mucin-1 and mucin-2 mRNA. The study also demonstrated that PA inhibited the DSS-induced cell death signaling by modulating the apoptosis related Bax and Bcl-2 proteins and down-regulating the necroptosis related RIP3 and MLKL proteins. By comparison, up-regulation of IDO-1 and TPH-1 protein expression in DSS group was suppressed by PA, which was in line with the declined levels of kynurenine (Kyn) and 5-hydroxytryptophan (5-HTP) in plasma. The therapeutic effect of PA was evidently reduced when Kyn was given to mice. In summary, the study successfully demonstrated that PA ameliorated DSS-induced mice acute colitis by suppressing inflammation, maintaining the integrity of intestinal epithelial barrier, inhibiting cell death signaling, and suppressing tryptophan catabolism. The results provided valuable information and guidance for using PA in treatment of UC. PMID: 28456683 [PubMed - as supplied by publisher]

Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease. Arch Biochem Biophys. 2017 Apr 26;: Authors: Nababan S, Nishiumi S, Kawano Y, Kobayashi T, Yoshida M, Azuma T Abstract BACKGROUND: This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD). METHODS: We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNFα or IL1β. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS. RESULTS: The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild fibrosis, obesity, and hypercholesterolemia displayed significantly higher hepatic and plasma levels of free adrenic acid (p < 0.05). The accumulated adrenic acid in the CDAHFD-fed db/db mice was associated with increased expression of ELOVL2 and 5, and the suppression of the acyl-CoA oxidase 1 gene during peroxisomal β-oxidation. The pretreatment of HepG2 cells with adrenic acid enhanced their cytokine-induced cytokines and chemokines mRNA expression. In NAFLD patients, the group with the highest ALT levels exhibited higher plasma adrenic acid concentrations than the other ALT groups (p-value for trend: <0.001). CONCLUSION: Data obtained demonstrated that adrenic acid accumulation contributes to disease progression in NAFLD. PMID: 28456640 [PubMed - as supplied by publisher]

Corrigendum to "Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D3 administration" [Metabolism vol. 70, May 2017, pages 31-41]. Metabolism. 2017 Apr 26;: Authors: Alvarez JA, Chong EY, Walker DI, Chandler JD, Michalski ES, Grossmann RE, Uppal K, Li S, Frediani JK, Tirouvanziam R, Tran VT, Tangpricha V, Jones DP, Ziegler TR PMID: 28456337 [PubMed - as supplied by publisher]

Using precursor ion scan of 184 with liquid chromatography-electrospray ionization-tandem mass spectrometry for concentration normalization in cellular lipidomic studies. Anal Chim Acta. 2017 Jun 08;971:68-77 Authors: Chao HC, Chen GY, Hsu LC, Liao HW, Yang SY, Wang SY, Li YL, Tang SC, Tseng YJ, Kuo CH Abstract Cellular lipidomic studies have been favored approaches in many biomedical research areas. To provide fair comparisons of the studied cells, it is essential to perform normalization of the determined concentration before lipidomic analysis. This study proposed a cellular lipidomic normalization method by measuring the phosphatidylcholine (PC) and sphingomyelin (SM) contents in cell extracts. To provide efficient analysis of PC and SM in cell extracts, flow injection analysis-electrospray ionization-tandem mass spectrometry (FIA-ESI-MS/MS) with a precursor ion scan (PIS) of m/z 184 was used, and the parameters affecting the performance of the method were optimized. Good linearity could be observed between the cell extract dilution factor and the reciprocal of the total ion chromatogram (TIC) area in the PIS of m/z 184 within the dilution range of 1- to 16-fold (R(2) = 0.998). The calibration curve could be used for concentration adjustment of the unknown concentration of a cell extract. The intraday and intermediate precisions were below 10%. The accuracy ranged from 93.0% to 105.6%. The performance of the new normalization method was evaluated using different numbers of HCT-116 cells. Sphingosine, ceramide (d18:1/18:0), SM (d18:1/18:0) and PC (16:1/18:0) were selected as the representative test lipid species, and the results showed that the peak areas of each lipid species obtained from different cell numbers were within a 20% variation after normalization. Finally, the PIS of 184 normalization method was applied to study ischemia-induced neuron injury using oxygen and glucose deprivation (OGD) on primary neuronal cultured cells. Our results showed that the PIS of 184 normalization method is an efficient and effective approach for concentration normalization in cellular lipidomic studies. PMID: 28456285 [PubMed - in process]

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Related Articles Microbial use of low molecular weight DOM in filtered and unfiltered freshwater: Role of ultra-small microorganisms and implications for water quality monitoring. Sci Total Environ. 2017 Apr 24;598:377-384 Authors: Brailsford FL, Glanville HC, Marshall MR, Golyshin PN, Johnes PJ, Yates CA, Owen AT, Jones DL Abstract Dissolved organic matter (DOM) plays a central role in regulating productivity and nutrient cycling in freshwaters. It is therefore vital that we can representatively sample and preserve DOM in freshwaters for subsequent analysis. Here we investigated the effect of filtration, temperature (5 and 25°C) and acidification (HCl) on the persistence of low molecular weight (MW) dissolved organic carbon (DOC), nitrogen (DON) and orthophosphate in oligotrophic and eutrophic freshwater environments. Our results showed the rapid loss of isotopically-labelled glucose and amino acids from both filtered (0.22 and 0.45μm) and unfiltered waters. We ascribe this substrate depletion in filtered samples to the activity of ultra-small (<0.45μm) microorganisms (bacteria and archaea) present in the water. As expected, the rate of C, N and P loss was much greater at higher temperatures and was repressed by the addition of HCl. Based on our results and an evaluation of the protocols used in recently published studies, we conclude that current techniques used to sample water for low MW DOM characterisation are frequently inadequate and lack proper validation. In contrast to the high degree of analytical precision and rigorous statistical analysis of most studies, we argue that insufficient consideration is still given to the presence of ultra-small microorganisms and potential changes that can occur in the low MW fraction of DOM prior to analysis. PMID: 28448929 [PubMed - as supplied by publisher]

Related Articles Chemodiversity of two closely related tetraploid Centaurium species and their hexaploid hybrid: Metabolomic search for high-resolution taxonomic classifiers. Phytochemistry. 2017 Apr 24;140:27-44 Authors: Banjanac T, Dragićević M, Šiler B, Gašić U, Bohanec B, Nestorović Živković J, Trifunović S, Mišić D Abstract Species within the genus Centaurium readily hybridize and polyploid complexes are often seen in natural populations. We describe phytochemical profiles of newly discovered allohexaploid hybrid, here named Centaurium pannonicum, and its parental tetraploid species C. erythraea and rare C. littorale ssp. compressum. Our aim was to examine chemodiversity of these taxa in the area of Vojvodina (North Serbia) and to perform metabolomics search for chemical classifiers which would provide high resolution discrimination of parental and hybrid individuals. In sum, UHPLC-MS/MS Orbitrap metabolomics fingerprinting revealed seventy compounds in methanol extracts. Despite the lack of qualitative chemical novelty in hybrid plants, UHPLC-qqqMS targeted metabolomics approach, aimed at three secoiridoid compounds and seventeen phenolics, pointed to considerable differences in quantitative composition of these dominant compounds among the plant taxa studied. In addition to the difference in the ploidy levels, the hybrid taxon was well distinguished from both parental species based on metabolite profiles, and, for most individuals, positioned intermediately to the parental taxa in both PCA and hierarchical clustering. After optimizing and comparing several statistical learning methods, it was possible to narrow the number of taxonomic classifiers to five (three xanthones, one secoiridoid glycoside, and one phenolic acid), while increasing the differentiation resolution. The presented metabolomics approach will certainly, along with morphometrics and molecular genetics studies, have high impact on further elucidation of complex relationships among taxa within the genus Centaurium. PMID: 28448798 [PubMed - as supplied by publisher]

Related Articles Systems biology guided by XCMS Online metabolomics. Nat Methods. 2017 Apr 27;14(5):461-462 Authors: Huan T, Forsberg EM, Rinehart D, Johnson CH, Ivanisevic J, Benton HP, Fang M, Aisporna A, Hilmers B, Poole FL, Thorgersen MP, Adams MWW, Krantz G, Fields MW, Robbins PD, Niedernhofer LJ, Ideker T, Majumder EL, Wall JD, Rattray NJW, Goodacre R, Lairson LL, Siuzdak G PMID: 28448069 [PubMed - in process]

Related Articles Effects of Histidine Supplementation on Global Serum and Urine 1H NMR-based Metabolomics and Serum Amino Acid Profiles in Obese Women from a Randomized Controlled Study. J Proteome Res. 2017 Apr 27;: Authors: Du S, Sun S, Liu L, Zhang Q, Guo F, Li C, Feng R, Sun C Abstract The aim of current study was to investigate the metabolic changes associated with histidine supplementation in serum and urine metabolic signatures and serum amino acid (AA) profiles. Serum and urine 1H NMR-based metabolomics and serum AAs profiles were employed in thirty two and thirty seven obese women with metabolic syndrome (MetS) intervened with placebo or histidine for 12 weeks. Multivariable statistical analysis were conducted to define characteristic metabolites. In serum 1H NMR metabolic profiles, increases in histidine, glutamine, aspartate, glycine, choline, and trimethylamine-N-oxide (TMAO) were observed, meanwhile, decreases in cholesterol, triglycerides, fatty acids and unsaturated lipids, acetone, and α/β-Glucose were exhibited after histidine supplement. In urine 1H NMR metabolic profiles, citrate, creatinine/creatine, methylguanidine and betaine + TMAO were higher, while, hippurate were lower in histidine supplement group. In serum AA profiles, ten AAs changed after histidine supplementation, including increased histidine, glycine, alanine, lysine, asparagine and tyrosine, and decreased leucine, isoleucine, ornithine and citrulline. The study showed a systemic metabolic response in serum and urine metabolomics and AA profiles to histidine supplementation, showing significantly changed metabolism in AAs, lipid and glucose in obese women with MetS. PMID: 28447460 [PubMed - as supplied by publisher]

Related Articles A Computational Selection of Metabolite Biomarkers Using Emerging Pattern Mining. A Case Study in human Hepatocellular Carcinoma. J Proteome Res. 2017 Apr 27;: Authors: Poezevara G, Lozano S, Cuissart B, Bureau R, Bureau P, Croixmarie V, Vayer P, Lepailleur A Abstract The biomarker development in metabolomics aims at discriminating diseased from normal subjects and at creating a predictive model which can be used to diagnose new subjects. From a case study on human hepatocellular carcinoma (HCC), we studied for the first time the potential usefulness of the emerging patterns (EPs) which comes from the data mining domain. When applied to a metabolomics dataset labeled with two classes (e.g. HCC patients vs healthy subjects), EP mining can capture differentiating combinations of metabolites between the two classes. We observed that the so-called jumping emerging patterns (JEPs), which correspond to the combinations of metabolites that occur in only one of the two classes, achieved better performance than individual biomarkers. Particularly, the implementation of the JEPs in a rules-based diagnostic tool drastically reduced the false positive rate, i.e the rate of healthy subjects predicted as HCC patients. PMID: 28447453 [PubMed - as supplied by publisher]

Related Articles Multimode Separation for Metabolomics and Complex Environmental Samples. Chimia (Aarau). 2017 Apr 26;71(4):242 Authors: Ammann AA, Suter MJ PMID: 28446345 [PubMed - in process]

Related Articles Combined GC- and UHPLC-HR-MS Based Metabolomics to Analyze Durable Anti-fungal Resistance Processes in Cereals. Chimia (Aarau). 2017 Apr 26;71(4):156-159 Authors: Bucher R, Veyel D, Willmitzer L, Krattinger S, Keller B, Biglera L Abstract Introduction of durable resistance genes in crops is an important strategy to prevent yield loss caused by pathogens. The durable multi-pathogen resistance gene Lr34 originating from wheat is widely used in breeding, and is functionally transferable to barley and rice. The molecular resistance mechanism of Lr34, encoding for an adenosine triphosphate-binding cassette transporter, is not known yet. To understand the molecular function and the defense response of durable disease resistance in cereals, the metabolic response of Lr34 was investigated in, except for the Lr34 gene, genetically identical lines of barley, rice and wheat. A broad range of compounds including primary, secondary and lipophilic metabolites were analyzed by a combination of gas (GC) and liquid chromatography (LC) mass spectrometry (MS) based methods. Data from metabolomics correlated well with transcriptomics data for plant defense responses such as the formation of anti-fungal hordatines or the components of the glyoxylate cycle. Induction of the glyoxylate cycle found in transgenic Lr34 rice grown in the greenhouse was confirmed in field-grown natural Lr34 wheat. Constitutively active plant defense responses were observed in the different cereals. PMID: 28446328 [PubMed - in process]

Related Articles Comprehensive analysis of phospholipids and glycolipids in the opportunistic pathogen Enterococcus faecalis. PLoS One. 2017;12(4):e0175886 Authors: Rashid R, Cazenave-Gassiot A, Gao IH, Nair ZJ, Kumar JK, Gao L, Kline KA, Wenk MR Abstract Enterococcus faecalis is a Gram-positive, opportunistic, pathogenic bacterium that causes a significant number of antibiotic-resistant infections in hospitalized patients. The development of antibiotic resistance in hospital-associated pathogens is a formidable public health threat. In E. faecalis and other Gram-positive pathogens, correlations exist between lipid composition and antibiotic resistance. Resistance to the last-resort antibiotic daptomycin is accompanied by a decrease in phosphatidylglycerol (PG) levels, whereas multiple peptide resistance factor (MprF) converts anionic PG into cationic lysyl-PG via a trans-esterification reaction, providing resistance to cationic antimicrobial peptides. Unlike previous studies that relied on thin layer chromatography and spectrophotometry, we have performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) directly on lipids extracted from E. faecalis, and quantified the phospholipids through multiple reaction monitoring (MRM). In the daptomycin-sensitive E. faecalis strain OG1RF, we have identified 17 PGs, 8 lysyl-PGs (LPGs), 23 cardiolipins (CL), 3 glycerophospho-diglucosyl-diacylglycerols (GPDGDAG), 5 diglucosyl-diacylglycerols (DGDAG), 3 diacylglycerols (DAGs), and 4 triacylglycerols (TAGs). We have quantified PG and shown that PG levels vary during growth of E. faecalis in vitro. We also show that two daptomycin-resistant (DapR) strains of E. faecalis have substantially lower levels of PG and LPG levels. Since LPG levels in these strains are lower, daptomycin resistance is likely due to the reduction in PG. This lipidome map is the first comprehensive analysis of membrane phospholipids and glycolipids in the important human pathogen E. faecalis, for which antimicrobial resistance and altered lipid homeostasis have been intimately linked. PMID: 28423018 [PubMed - indexed for MEDLINE]

Related Articles Development and validation of a UHPLC-ESI-MS/MS method for the simultaneous quantification of mammal lysophosphatidylcholines and lysophosphatidylethanolamines in serum. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Apr 18;1055-1056:86-97 Authors: Suárez-García S, Arola L, Pascual-Serrano A, Arola-Arnal A, Aragonès G, Bladé C, Suárez M Abstract Recent investigations based on non-targeted metabolomics have proposed lysophospholipids (Lyso-PLs) as biomarkers of different diseases. In particular, lysophosphatidylcholines (Lyso-PCs) and lysophosphatidylethanolamines (Lyso-PEs) have been associated with serious lipid pathologies. Methods to determine the different molecular species in a biological sample and to quantify even less abundant species are required for the evaluation of the Lyso-PL pattern as a novel comprehensive biomarker of dyslipidemia. This study describes the development and validation of an ultra-high-performance liquid chromatography coupled to tandem mass spectrometry assay for the determination of a large number of Lyso-PCs and Lyso-PEs in biological samples. The method was validated in rat serum using two simple methanol-based extractions with low sample volumes (5-50μL) that covered the wide concentration range of these metabolites. In total, thirty-one Lyso-PLs were separated and quantified with low method limits of detection and quantification, reaching values of 0.2 and 0.8nM, respectively. The method was subsequently applied in the identification of Lyso-PL-related changes produced by the chronic intake of a cafeteria diet. The results showed alterations in the majority of Lyso-PCs and Lyso-PEs in rat serum. Furthermore, multivariate analysis indicated that the comprehensive evaluation of serum Lyso-PLs could be an excellent indicator of the nutritional phenotype associated with an increased risk of lipid disorders. PMID: 28445851 [PubMed - as supplied by publisher]