Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Accurate Identification of Unknown and Known Metabolic Mixture Components by Combining 3D NMR with FT-ICR MS/MS.

Fri, 11/08/2017 - 14:23
Related Articles Accurate Identification of Unknown and Known Metabolic Mixture Components by Combining 3D NMR with FT-ICR MS/MS. J Proteome Res. 2017 Aug 10;: Authors: Wang C, He L, Li D, Bruschweiler-Li L, Marshall AG, Bruschweiler R Abstract Metabolite identification in metabolomics samples is a key step that critically impacts downstream analysis. We recently introduced the SUMMIT NMR/MS hybrid approach for the identification of the molecular structure of unknown metabolites, based on the combination of NMR, mass spectrometry (MS), and combinatorial cheminformatics. Here, we demonstrate the feasibility of the approach for an untargeted analysis of both a model mixture and E. coli cell lysate, based on 2D/3D NMR experiments in combination with FT-ICR MS and MS/MS data. For 19 of the 25 model metabolites SUMMIT yielded complete structures that matched those in the mixture independent of database information. Of those, 7 top-ranked structures matched those in the mixture, and 4 of those were further validated by positive ion MS/MS. For 5 metabolites, not part of the 19 metabolites, correct molecular structural motifs could be identified. For E. coli, SUMMIT MS/NMR identified 20 previously known metabolites with 3 or more 1H spins independent of database information. Moreover, for 15 unknown metabolites, molecular structural fragments were determined consistent with their spin systems and chemical shifts. By providing structural information for entire metabolites or molecular fragments, SUMMIT MS/NMR greatly assists the targeted or untargeted analysis of complex mixtures of unknown compounds. PMID: 28795575 [PubMed - as supplied by publisher]

Plasma Metabolomics Reveals Steroidal Alkaloids as Novel Biomarkers of Tomato Intake in Mice.

Fri, 11/08/2017 - 14:23
Related Articles Plasma Metabolomics Reveals Steroidal Alkaloids as Novel Biomarkers of Tomato Intake in Mice. Mol Nutr Food Res. 2017 Aug 09;: Authors: Cichon MJ, Riedl KM, Wan L, Thomas-Ahner JM, Francis DM, Clinton SK, Schwartz SJ Abstract SCOPE: Diets rich in tomato products are associated with a reduced risk of various chronic disease processes. The carotenoid lycopene is most intensely studied as the bioactive mediating health effects, yet tomatoes contain an array of phytochemicals. We conducted an untargeted metabolomics study on blood plasma to identify novel markers of tomato consumption absorbed from the diet and released into the bloodstream in mice. METHODS AND RESULTS: Male mice were fed a control AIN-93G diet or the same diet supplemented with 0.25% lycopene beadlets, or 10% freeze-dried red tomato, tangerine tomato, or low-carotenoid tomato for 4 weeks. Untargeted UHPLC-QTOF-MS data acquisition and differential analysis of plasma metabolites revealed several structurally related deglycosylated tomato steroidal alkaloids, including tomatidine and hydroxylated/desaturated derivatives, in plasma after the consumption of all 3 tomato varieties. Additionally, plasma metabolite profiles reflected glycoalkaloid forms found in the tomato diets. CONCLUSION: Dietary tomato glycoalkaloids are cleaved during digestion to aglycones and further metabolized post-absorption. Steroidal alkaloids in plasma may serve as novel and specific biomarkers of tomato consumption and represent a class of phytochemical metabolites that could potentially have in vivo bioactivity impacting health and disease processes. This article is protected by copyright. All rights reserved. PMID: 28795489 [PubMed - as supplied by publisher]

Mass spectrometry data of metabolomics analysis of Nepenthes pitchers.

Fri, 11/08/2017 - 14:23
Related Articles Mass spectrometry data of metabolomics analysis of Nepenthes pitchers. Data Brief. 2017 Oct;14:295-297 Authors: Rosli MAF, Azizan KA, Baharum SN, Goh HH Abstract Hybridisation plays a significant role in the evolution and diversification of plants. Hybridisation among Nepenthes species is extensive, either naturally or man-made. To investigate the effects of hybridisation on the chemical compositions, we carried out metabolomics study on pitcher tissue of Nepenthes ampullaria, Nepenthes rafflesiana and their hybrid, Nepenthes × hookeriana. Pitcher samples were harvested and extracted in methanol:chloroform:water via sonication-assisted extraction before analysed using LC-TOF-MS. MS data were analysed using XCMS online version 2.2.5. This is the first MS data report towards the profiling, identification and comprehensive comparison of metabolites present in Nepenthes species. PMID: 28795107 [PubMed]

Metabolomic Evaluation of the Consequences of Plasma Cystathionine Elevation in Adults with Stable Angina Pectoris.

Fri, 11/08/2017 - 14:23
Related Articles Metabolomic Evaluation of the Consequences of Plasma Cystathionine Elevation in Adults with Stable Angina Pectoris. J Nutr. 2017 Aug 09;: Authors: DeRatt BN, Ralat MA, Lysne V, Tayyari F, Dhar I, Edison AS, Garrett TJ, Midttun Ø, Ueland PM, Nygård OK, Gregory JF Abstract Background: An elevated circulating cystathionine concentration, which arises in part from insufficiencies of vitamin B-6, B-12, or folate, has been shown to be associated with cardiovascular disease (CVD) risk. Hydrogen sulfide (H2S) is a gasotransmitter involved in vasodilation, neuromodulation, and inflammation. Most endogenously produced H2S is formed by pyridoxal phosphate (PLP)-dependent enzymes by noncanonical reactions of the transsulfuration pathway that yield H2S concurrently form lanthionine and homolanthionine. Thus, plasma lanthionine and homolanthionine concentrations can provide relative information about H2S production in vivo.Objective: To determine the metabolic consequences of an elevated plasma cystathionine concentration in adults with stable angina pectoris (SAP), we conducted both targeted and untargeted metabolomic analyses.Methods: We conducted NMR and LC-mass spectrometry (MS) metabolomic analyses on a subset of 80 plasma samples from the Western Norway Coronary Angiography Cohort and selected, based on plasma cystathionine concentrations, a group with high cystathionine concentrations [1.32 ± 0.60 μmol/L (mean ± SD); n = 40] and a group with low cystathionine concentrations [0.137 ± 0.011 μmol/L (mean ± SD); n = 40]. Targeted and untargeted metabolomic analyses were performed and assessed with the use of Student's t tests corrected for multiple testing. Overall differences between the cystathionine groups were assessed by untargeted NMR and LC-MS metabolomic methods and evaluated by partial least squares discriminant analysis (PLS-DA) with significant discriminating metabolites identified with 99% confidence.Results: Subjects with high cystathionine concentrations had 75% higher plasma lanthionine concentrations (0.12 ± 0.044 μmol/L) than subjects with low cystathionine concentrations [0.032 ± 0.013 μmol/L (P < 0.001)]. Although plasma homolanthionine concentrations were notably higher than lanthionine concentrations, they were not different between the groups (P = 0.47). PLS-DA results showed that a high plasma cystathionine concentration in SAP was associated with higher glucose, branched-chain amino acids, and phenylalanine concentrations, lower kidney function, and lower glutathione and plasma PLP concentrations due to greater catabolism. The high-cystathionine group had a greater proportion of subjects in the postprandial state.Conclusion: These data suggest that metabolic perturbations consistent with higher CVD risk exist in SAP patients with elevated plasma cystathionine concentrations. PMID: 28794210 [PubMed - as supplied by publisher]

Estimation of Chicken Intake by Adults Using Metabolomics-Derived Markers.

Fri, 11/08/2017 - 14:23
Related Articles Estimation of Chicken Intake by Adults Using Metabolomics-Derived Markers. J Nutr. 2017 Aug 09;: Authors: Yin X, Gibbons H, Rundle M, Frost G, McNulty BA, Nugent AP, Walton J, Flynn A, Gibney MJ, Brennan L Abstract Background: Improved assessment of meat intake with the use of metabolomics-derived markers can provide objective data and could be helpful in clarifying proposed associations between meat intake and health.Objective: The objective of this study was to identify novel markers of chicken intake using a metabolomics approach and use markers to determine intake in an independent cohort.Methods: Ten participants [age: 62 y; body mass index (in kg/m(2)): 28.25] in the NutriTech food intake study consumed increasing amounts of chicken, from 88 to 290 g/d, in a 3-wk span. Urine and blood samples were analyzed by nuclear magnetic resonance and mass spectrometry, respectively. A multivariate data analysis was performed to identify markers associated with chicken intake. A calibration curve was built based on dose-response association using NutriTech data. A Bland-Altman analysis evaluated the agreement between reported and calculated chicken intake in a National Adult Nutrition Survey cohort.Results: Multivariate data analysis of postprandial and fasting urine samples collected in participants in the NutriTech study revealed good discrimination between high (290 g/d) and low (88 g/d) chicken intakes. Urinary metabolite profiles showed differences in metabolite levels between low and high chicken intakes. Examining metabolite profiles revealed that guanidoacetate increased from 1.47 to 3.66 mmol/L following increasing chicken intakes from 88 to 290 g/d (P < 0.01). Using a calibration curve developed from the NutriTech study, chicken intake was calculated through the use of data from the National Adult Nutrition Survey, in which consumers of chicken had a higher guanidoacetate excretion (0.70 mmol/L) than did nonconsumers (0.47 mmol/L; P < 0.01). A Bland-Altman analysis revealed good agreement between reported and calculated intakes, with a bias of -30.2 g/d. Plasma metabolite analysis demonstrated that 3-methylhistidine was a more suitable indicator of chicken intake than 1-methylhistidine.Conclusions: Guanidoacetate was successfully identified and confirmed as a marker of chicken intake, and its measurement in fasting urine samples could be used to determine chicken intake in a free-living population. This trial was registered at clinicaltrials.gov as NCT01684917. PMID: 28794208 [PubMed - as supplied by publisher]

The Human Serum Metabolome of Vitamin B-12 Deficiency and Repletion, and Associations with Neurological Function in Elderly Adults.

Fri, 11/08/2017 - 14:23
Related Articles The Human Serum Metabolome of Vitamin B-12 Deficiency and Repletion, and Associations with Neurological Function in Elderly Adults. J Nutr. 2017 Aug 09;: Authors: Brito A, Grapov D, Fahrmann J, Harvey D, Green R, Miller JW, Fedosov SN, Shahab-Ferdows S, Hampel D, Pedersen TL, Fiehn O, Newman JW, Uauy R, Allen LH Abstract Background: The specific metabolomic perturbations that occur in vitamin B-12 deficiency, and their associations with neurological function, are not well characterized.Objective: We sought to characterize the human serum metabolome in subclinical vitamin B-12 deficiency and repletion.Methods: A before-and-after treatment study provided 1 injection of 10 mg vitamin B-12 (with 100 mg pyridoxine and 100 mg thiamin) to 27 community-dwelling elderly Chileans (∼74 y old) with vitamin B-12 deficiency, as evaluated with serum vitamin B-12, total plasma homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin. The combined indicator of vitamin B-12 status (cB-12) was computed. Targeted metabolites [166 acylcarnitines, amino acids, sugars, glycerophospholipids, and sphingolipids (liquid chromatography-tandem mass spectrometry)], and untargeted metabolites [247 chemical entities (gas chromatography time-of-flight mass spectrometry)] were measured at baseline and 4 mo after treatment. A peripheral nerve score was developed. Differences before and after treatment were examined. For targeted metabolomics, the data from 18 individuals with adequate vitamin B-12 status (selected from the same population) were added to the before-and-after treatment data set. Network visualizations and metabolic pathways are illustrated.Results: The injection increased serum vitamin B-12, holotranscobalamin, and cB-12 (P < 0.001), and reduced tHcy and serum MMA (P < 0.001). Metabolomic changes from before to after treatment included increases (P < 0.001) in acylcarnitines, plasmalogens, and other phospholipids, whereas proline and other intermediaries of one-carbon metabolism-that is, methionine and cysteine-were reduced (P < 0.001). Direct significant correlations (P < 0.05 after the false discovery rate procedure) were identified between acylcarnitines, plasmalogens, phospholipids, lyso-phospholipids, and sphingomyelins compared with vitamin B-12 status and nerve function. Multiple connections were identified with primary metabolites (e.g., an inverse relation between vitamin B-12 markers and tryptophan, tyrosine, and pyruvic, succinic, and citric acids, and a direct correlation between the nerve score and arginine).Conclusions: The human serum metabolome in vitamin B-12 deficiency and the changes that occur after supplementation are characterized. Metabolomics revealed connections between vitamin B-12 status and serum metabolic markers of mitochondrial function, myelin integrity, oxidative stress, and peripheral nerve function, including some previously implicated in Alzheimer and Parkinson diseases. This trial was registered at www.controlled-trials.com as ISRCTN02694183. PMID: 28794205 [PubMed - as supplied by publisher]

Uptake and transformations of engineered nanomaterials: Critical responses observed in terrestrial plants and the model plant Arabidopsis thaliana.

Fri, 11/08/2017 - 14:23
Related Articles Uptake and transformations of engineered nanomaterials: Critical responses observed in terrestrial plants and the model plant Arabidopsis thaliana. Sci Total Environ. 2017 Aug 05;607-608:1497-1516 Authors: Montes A, Bisson MA, Gardella JA, Aga DS Abstract With the applications of engineered nanomaterials (ENMs) continually expanding and production quickly growing, residues of ENMs will end up in the environment at levels that may be harmful to non-target organisms. Many of the tunable properties that have made them desirable, such as type, size, charge, or coating, also contribute to the current difficulties in understanding the fate of ENMs in the environment. This review article focuses on studies that investigate plant-ENM interactions, including techniques used to study these interactions and documented plant responses due to the phytotoxic effects of ENMs. The many variables which can be altered for an experiment, such as type, size, and concentration of ENMs, make it difficult to formulate generalizations about the uptake mechanism involved, or to make an inference on the subcellular localization and distribution of the internalized ENMs in plant tissue. In order to avoid these challenges, studies can utilize a model organism such as Arabidopsis thaliana, and a combination of analytical techniques that can reveal complementary information in order to assess how the different experimental conditions influence the uptake and phytotoxicity of ENMs. This review presents recent studies regarding plant-ENM interactions employing Arabidopsis to demonstrate how the use of this model plant can advance our understanding of plant-ENM interactions and guide additional studies using other plant species. Overarching results suggest that more sensitive tests and consistency in experimental designs are needed to fully assess and understand the phytotoxic effects of ENMs in the environment. PMID: 28793406 [PubMed - as supplied by publisher]

Resetting microbiota by Lactobacillus reuteri inhibits T reg deficiency-induced autoimmunity via adenosine A2A receptors.

Fri, 11/08/2017 - 14:23
Related Articles Resetting microbiota by Lactobacillus reuteri inhibits T reg deficiency-induced autoimmunity via adenosine A2A receptors. J Exp Med. 2017 Jan;214(1):107-123 Authors: He B, Hoang TK, Wang T, Ferris M, Taylor CM, Tian X, Luo M, Tran DQ, Zhou J, Tatevian N, Luo F, Molina JG, Blackburn MR, Gomez TH, Roos S, Rhoads JM, Liu Y Abstract Regulatory T (T reg) cell deficiency causes lethal, CD4(+) T cell-driven autoimmune diseases. Stem cell transplantation is used to treat these diseases, but this procedure is limited by the availability of a suitable donor. The intestinal microbiota drives host immune homeostasis by regulating the differentiation and expansion of T reg, Th1, and Th2 cells. It is currently unclear if T reg cell deficiency-mediated autoimmune disorders can be treated by targeting the enteric microbiota. Here, we demonstrate that Foxp3(+) T reg cell deficiency results in gut microbial dysbiosis and autoimmunity over the lifespan of scurfy (SF) mouse. Remodeling microbiota with Lactobacillus reuteri prolonged survival and reduced multiorgan inflammation in SF mice. L. reuteri changed the metabolomic profile disrupted by T reg cell deficiency, and a major effect was to restore levels of the purine metabolite inosine. Feeding inosine itself prolonged life and inhibited multiorgan inflammation by reducing Th1/Th2 cells and their associated cytokines. Mechanistically, the inhibition of inosine on the differentiation of Th1 and Th2 cells in vitro depended on adenosine A2A receptors, which were also required for the efficacy of inosine and of L. reuteri in vivo. These results reveal that the microbiota-inosine-A2A receptor axis might represent a potential avenue for combatting autoimmune diseases mediated by T reg cell dysfunction. PMID: 27994068 [PubMed - indexed for MEDLINE]

Blockade of Glutamine Synthetase Enhances Inflammatory Response in Microglial Cells.

Fri, 11/08/2017 - 14:23
Related Articles Blockade of Glutamine Synthetase Enhances Inflammatory Response in Microglial Cells. Antioxid Redox Signal. 2017 Mar 10;26(8):351-363 Authors: Palmieri EM, Menga A, Lebrun A, Hooper DC, Butterfield DA, Mazzone M, Castegna A Abstract AIMS: Microglial cells are brain-resident macrophages engaged in surveillance and maintained in a constant state of relative inactivity. However, their involvement in autoimmune diseases indicates that in pathological conditions microglia gain an inflammatory phenotype. The mechanisms underlying this change in the microglial phenotype are still unclear. Since metabolism is an important modulator of immune cell function, we focused our attention on glutamine synthetase (GS), a modulator of the response to lipopolysaccharide (LPS) activation in other cell types, which is expressed by microglia. RESULTS: GS inhibition enhances release of inflammatory mediators of LPS-activated microglia in vitro, leading to perturbation of the redox balance and decreased viability of cocultured neurons. GS inhibition also decreases insulin-mediated glucose uptake in microglia. In vivo, microglia-specific GS ablation enhances expression of inflammatory markers upon LPS treatment. In the spinal cords from experimental autoimmune encephalomyelitis (EAE), GS expression levels and glutamine/glutamate ratios are reduced. INNOVATION: Recently, metabolism has been highlighted as mediator of immune cell function through the discovery of mechanisms that (behind these metabolic changes) modulate the inflammatory response. The present study shows for the first time a metabolic mechanism mediating microglial response to a proinflammatory stimulus, pointing to GS activity as a master modulator of immune cell function and thus unraveling a potential therapeutic target. CONCLUSIONS: Our study highlights a new role of GS in modulating immune response in microglia, providing insights into the pathogenic mechanisms associated with inflammation and new strategies of therapeutic intervention. Antioxid. Redox Signal. 26, 351-363. PMID: 27758118 [PubMed - indexed for MEDLINE]

NOX4-dependent fatty acid oxidation promotes NLRP3 inflammasome activation in macrophages.

Fri, 11/08/2017 - 14:23
Related Articles NOX4-dependent fatty acid oxidation promotes NLRP3 inflammasome activation in macrophages. Nat Med. 2016 Sep;22(9):1002-12 Authors: Moon JS, Nakahira K, Chung KP, DeNicola GM, Koo MJ, Pabón MA, Rooney KT, Yoon JH, Ryter SW, Stout-Delgado H, Choi AM Abstract Altered metabolism has been implicated in the pathogenesis of inflammatory diseases. NADPH oxidase 4 (NOX4), a source of cellular superoxide anions, has multiple biological functions that may be of importance in inflammation and in the pathogenesis of human metabolic diseases, including diabetes. However, the mechanisms by which NOX4-dependent metabolic regulation affect the innate immune response remain unclear. Here we show that deficiency of NOX4 resulted in reduced expression of carnitine palmitoyltransferase 1A (CPT1A), which is a key mitochondrial enzyme in the fatty acid oxidation (FAO) pathway. The reduced FAO resulted in less activation of the nucleotide-binding domain, leucine-rich-repeat-containing receptor (NLR), pyrin-domain-containing 3 (NLRP3) inflammasome in human and mouse macrophages. In contrast, NOX4 deficiency did not inhibit the activation of the NLR family, CARD-domain-containing 4 (NLRC4), the NLRP1 or the absent in melanoma 2 (AIM2) inflammasomes. We also found that inhibition of FAO by etomoxir treatment suppressed NLRP3 inflammasome activation. Furthermore, Nox4-deficient mice showed substantial reduction in caspase-1 activation and in interleukin (IL)-1β and IL-18 production, and there was improved survival in a mouse model of NLRP3-mediated Streptococcus pneumoniae infection. The pharmacologic inhibition of NOX4 by either GKT137831, which is currently in phase 2 clinical trials, or VAS-2870 attenuated NLRP3 inflammasome activation. Our results suggest that NOX4-mediated FAO promotes NLRP3 inflammasome activation. PMID: 27455510 [PubMed - indexed for MEDLINE]

Personalised Interventions-A Precision Approach for the Next Generation of Dietary Intervention Studies.

Thu, 10/08/2017 - 13:58
Related Articles Personalised Interventions-A Precision Approach for the Next Generation of Dietary Intervention Studies. Nutrients. 2017 Aug 09;9(8): Authors: de Roos B, Brennan L Abstract Diet is a key modifiable risk factor for non-communicable diseases. However, we currently are not benefitting from the full potential of its protective effects. This is due to a number of reasons, including high individual variability in response to certain diets. It is now well acknowledged that in order to gain the full benefit of dietary regimes it is essential to take into account individual responses. With this in mind, the present review examines the concept of precision nutrition and the performance of n-of-1 studies, and discusses the development of certain approaches that will be critical for development of the concepts. PMID: 28792454 [PubMed - in process]

Special Issue: Cancer Metabolism.

Thu, 10/08/2017 - 13:58
Related Articles Special Issue: Cancer Metabolism. Metabolites. 2017 Aug 09;7(3): Authors: Basetti M Abstract This special issue is designed to present the latest research findings and developments in the field of cancer metabolism. Cancer is a complex disease and a common term used for more than 100 diseases, whereas metabolism describes a labyrinth of complex biochemical pathways in the cell. It is essential to understand metabolism in the context of cancer for the early detection of disease biomarkers and to find proper targets for potential treatments. The articles presented in this issue cover metabolic aspects of brain tumours, breast tumours, paraganglioma, and the metabolic activity of tumour suppressor gene p53. PMID: 28792436 [PubMed]

Advances in the analysis of "less-conventional" human body fluids: an overview of the ce- and hplc-ms applications in the years 2015-2017.

Thu, 10/08/2017 - 13:58
Related Articles Advances in the analysis of "less-conventional" human body fluids: an overview of the ce- and hplc-ms applications in the years 2015-2017. Electrophoresis. 2017 Aug 09;: Authors: Venere MD, Viglio S, Cagnone M, Bardoni A, Salvini R, Iadarola P Abstract Aim of this article is to focus the attention of the reader on the application of CE/MS and LC/MS to the analysis of human body fluids not currently used for the diagnosis of disorders and, for this reason, catalogued as "less-/non-conventional" fluids, i.e. tears, nasal secretions, cerumen, bronchoalveolar lavage fluid, sputum, exhaled breath condensate, nipple aspirate, breast milk, amniotic fluid, bile, seminal plasma, liposuction aspirate fluid and synovial fluid. The pool of articles presented in this report demonstrates that, rather than being neglected, these fluids are an important resource for the evaluation of possible pathologic conditions. Thus, being a sort of mirror that reflects the normal internal characteristics and disease state of an individual, they benefit of an increasing appreciation. This review follows a previous report of this series and covers the latest developments in this field which have been published in specialist journals in the years 2015-2017. This article is protected by copyright. All rights reserved. PMID: 28792066 [PubMed - as supplied by publisher]

Ambient mass spectrometry in metabolomics.

Thu, 10/08/2017 - 13:58
Related Articles Ambient mass spectrometry in metabolomics. Analyst. 2017 Aug 09;: Authors: Clendinen CS, Monge ME, Fernández FM Abstract Since the introduction of desorption electrospray ionization (DESI) mass spectrometry (MS), ambient MS methods have seen increased use in a variety of fields from health to food science. Increasing its popularity in metabolomics, ambient MS offers limited sample preparation, rapid and direct analysis of liquids, solids, and gases, in situ and in vivo analysis, and imaging. The metabolome consists of a constantly changing collection of small (<1.5 kDa) molecules. These include endogenous molecules that are part of primary metabolism pathways, secondary metabolites with specific functions such as signaling, chemicals incorporated in the diet or resulting from environmental exposures, and metabolites associated with the microbiome. Characterization of the responsive changes of this molecule cohort is the principal goal of any metabolomics study. With adjustments to experimental parameters, metabolites with a range of chemical and physical properties can be selectively desorbed and ionized and subsequently analyzed with increased speed and sensitivity. This review covers the broad applications of a variety of ambient MS techniques in four primary fields in which metabolomics is commonly employed. PMID: 28792022 [PubMed - as supplied by publisher]

Hyphenated MS-based targeted approaches in metabolomics.

Thu, 10/08/2017 - 13:58
Related Articles Hyphenated MS-based targeted approaches in metabolomics. Analyst. 2017 Aug 09;: Authors: Begou O, Gika HG, Wilson ID, Theodoridis G Abstract While global metabolic profiling (untargeted metabolomics) has been the center of much interest and research activity in the past few decades, more recently targeted metabolomics approaches have begun to gain ground. These analyses are, to an extent, more hypothesis-driven, as they focus on a set of pre-defined metabolites and aim towards their determination, often to the point of absolute quantification. The continuous development of the technological platforms used in these studies facilitates the analysis of large numbers of well-characterized metabolites present in complex matrices. The present review describes recent developments in the hyphenated chromatographic methods most often applied in targeted metabolomic/lipidomic studies (LC-MS/MS, CE-MS/MS, and GC-MS/MS), highlighting applications in the life and food/plant sciences. The review also underlines practical challenges-limitations that appear in such approaches. PMID: 28792021 [PubMed - as supplied by publisher]

Evolution of newborns urinary metabolomic profiles according to age and growth.

Thu, 10/08/2017 - 13:58
Related Articles Evolution of newborns urinary metabolomic profiles according to age and growth. J Proteome Res. 2017 Aug 09;: Authors: Scalabre A, Jobard E, Demède D, Gaillard S, Pontoizeau C, Mouriquand P, Elena-Herrmann B, Mure PY Abstract Improving the management of neonatal diseases and prevention of chronic diseases in adulthood requires a better comprehension of the complex maturational processes associated with newborns development. Urine-based metabolomic studies play a promising role in the fields of pediatrics and neonatology, relying on simple and non-invasive collection procedures while integrating a variety of factors such as genotype, nutritional state, lifestyle and diseases. Here, we investigate the influence of age, weight, height and gender on the urine metabolome during the first 4 months of life. Untargeted analysis of urine was carried out by 1H-Nuclear Magnetic Resonance (NMR) spectroscopy for 90 newborns under 4 months of age, and free of metabolic, nephrologic or urologic diseases. Supervised multivariate statistical analysis of the metabolic profiles revealed metabolites significantly associated with age, weight and height respectively. The tremendous growth occurring during the neonatal period is associated with specific modifications of newborns metabolism. Conversely, gender appears to have no impact on the urine metabolome during early infancy. These results allow a deeper understanding of newborn metabolic maturation and underline potential confounding factors in newborns metabolomics studies. We emphasize the need to systematically and precisely report children age, height and weight that impact urine metabolic profiles of infants. PMID: 28791867 [PubMed - as supplied by publisher]

Metabolomics and Proteomics of Brassica napus Guard Cells in Response to Low CO2.

Thu, 10/08/2017 - 13:58
Related Articles Metabolomics and Proteomics of Brassica napus Guard Cells in Response to Low CO2. Front Mol Biosci. 2017;4:51 Authors: Geng S, Yu B, Zhu N, Dufresne C, Chen S Abstract Stomatal guard cell response to various stimuli is an important process that balances plant carbon dioxide (CO2) uptake and water transpiration. Elevated CO2 induces stomatal closure, while low CO2 promotes stomatal opening. The signaling process of elevated CO2 induced stomatal closure has been extensively studied in recent years. However, the mechanism of low CO2 induced stomatal opening is not fully understood. Here we report metabolomic and proteomic responses of Brassica napus guard cells to low CO2 using hyphenated mass spectrometry technologies. A total of 411 metabolites and 1397 proteins were quantified in a time-course study of low CO2 effects. Metabolites and proteins that exhibited significant changes are overrepresented in fatty acid metabolism, starch and sucrose metabolism, glycolysis and redox regulation. Concomitantly, multiple hormones that promote stomatal opening increased in response to low CO2. Interestingly, jasmonic acid precursors were diverted to a branch pathway of traumatic acid biosynthesis. These results indicate that the low CO2 response is mediated by a complex crosstalk between different phytohormones. PMID: 28791296 [PubMed]

Gut Microbiome Response to Sucralose and Its Potential Role in Inducing Liver Inflammation in Mice.

Thu, 10/08/2017 - 13:58
Related Articles Gut Microbiome Response to Sucralose and Its Potential Role in Inducing Liver Inflammation in Mice. Front Physiol. 2017;8:487 Authors: Bian X, Chi L, Gao B, Tu P, Ru H, Lu K Abstract Sucralose is the most widely used artificial sweetener, and its health effects have been highly debated over the years. In particular, previous studies have shown that sucralose consumption can alter the gut microbiota. The gut microbiome plays a key role in processes related to host health, such as food digestion and fermentation, immune cell development, and enteric nervous system regulation. Inflammation is one of the most common effects associated with gut microbiome dysbiosis, which has been linked to a series of human diseases, such as diabetes and obesity. The aim of this study was to investigate the structural and functional effects of sucralose on the gut microbiota and associated inflammation in the host. In this study, C57BL/6 male mice received sucralose in their drinking water for 6 months. The difference in gut microbiota composition and metabolites between control and sucralose-treated mice was determined using 16S rRNA gene sequencing, functional gene enrichment analysis and metabolomics. Inflammatory gene expression in tissues was analyzed by RT-PCR. Alterations in bacterial genera showed that sucralose affects the gut microbiota and its developmental dynamics. Enrichment of bacterial pro-inflammatory genes and disruption in fecal metabolites suggest that 6-month sucralose consumption at the human acceptable daily intake (ADI) may increase the risk of developing tissue inflammation by disrupting the gut microbiota, which is supported by elevated pro-inflammatory gene expression in the liver of sucralose-treated mice. Our results highlight the role of sucralose-gut microbiome interaction in regulating host health-related processes, particularly chronic inflammation. PMID: 28790923 [PubMed]

Personomics and Precision Medicine.

Thu, 10/08/2017 - 13:58
Related Articles Personomics and Precision Medicine. Trans Am Clin Climatol Assoc. 2017;128:160-168 Authors: Ziegelstein RC Abstract The importance of knowing patients as individuals has been highlighted throughout the history of medicine. However, shorter visits, electronic documentation, reliance on technology, and increasing linguistic and cultural differences between patients and physicians create more challenges to effective communication than ever before. Perhaps more concerning is the greater emphasis on aspects of care considered more precisely measurable and quantifiable, the sum of which is sometimes felt to represent the patient better than knowledge of the patient himself. While genomics, proteomics, pharmacogenomics, metabolomics, and epigenomics promise enhanced diagnostics and therapeutics, understanding the unique circumstances of the person - what may be called personomics - is at least as critical to patient care. Such an understanding can only be developed when the relevant psychological, social, cultural, behavioral, and economic factors are obtained. Personomics determines how a disease reveals itself phenotypically and the way that disease and the individual with the disease respond to treatment. PMID: 28790500 [PubMed - in process]

Cellobiose Consumption Uncouples Extracellular Glucose Sensing and Glucose Metabolism in Saccharomyces cerevisiae.

Thu, 10/08/2017 - 13:58
Related Articles Cellobiose Consumption Uncouples Extracellular Glucose Sensing and Glucose Metabolism in Saccharomyces cerevisiae. MBio. 2017 Aug 08;8(4): Authors: Chomvong K, Benjamin DI, Nomura DK, Cate JHD Abstract Glycolysis is central to energy metabolism in most organisms and is highly regulated to enable optimal growth. In the yeast Saccharomyces cerevisiae, feedback mechanisms that control flux through glycolysis span transcriptional control to metabolite levels in the cell. Using a cellobiose consumption pathway, we decoupled glucose sensing from carbon utilization, revealing new modular layers of control that induce ATP consumption to drive rapid carbon fermentation. Alterations of the beta subunit of phosphofructokinase-1 (PFK2), H(+)-plasma membrane ATPase (PMA1), and glucose sensors (SNF3 and RGT2) revealed the importance of coupling extracellular glucose sensing to manage ATP levels in the cell. Controlling the upper bound of cellular ATP levels may be a general mechanism used to regulate energy levels in cells, via a regulatory network that can be uncoupled from ATP concentrations under perceived starvation conditions.IMPORTANCE Living cells are fine-tuned through evolution to thrive in their native environments. Genome alterations to create organisms for specific biotechnological applications may result in unexpected and undesired phenotypes. We used a minimal synthetic biological system in the yeast Saccharomyces cerevisiae as a platform to reveal novel connections between carbon sensing, starvation conditions, and energy homeostasis. PMID: 28790206 [PubMed - in process]

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