PubMed

Related Articles Serum and urine (1)H NMR-based metabolomics in the diagnosis of selected thyroid diseases. Sci Rep. 2017 Aug 22;7(1):9108 Authors: Wojtowicz W, Zabek A, Deja S, Dawiskiba T, Pawelka D, Glod M, Balcerzak W, Mlynarz P Abstract Early detection of nodular thyroid diseases including thyroid cancer is still primarily based on invasive procedures such as fine-needle aspiration biopsy. Therefore, there is a strong need for development of new diagnostic methods that could provide clinically useful information regarding thyroid nodular lesions in a non-invasive way. In this study we investigated (1)H NMR based metabolic profiles of paired urine and blood serum samples, that were obtained from healthy individuals and patients with nodular thyroid diseases. Estimation of predictive potential of metabolites was evaluated using chemometric methods and revealed that both urine and serum carry information sufficient to distinguish between patients with nodular lesions and healthy individuals. Data fusion allowed to further improve prediction quality of the models. However, stratification of tumor types and their differentiation in relation to each other was not possible. PMID: 28831094 [PubMed - in process]

Related Articles Large Scale Metabolic Profiling identifies Novel Steroids linked to Rheumatoid Arthritis. Sci Rep. 2017 Aug 22;7(1):9137 Authors: Yousri NA, Bayoumy K, Elhaq WG, Mohney RP, Emadi SA, Hammoudeh M, Halabi H, Masri B, Badsha H, Uthman I, Plenge R, Saxena R, Suhre K, Arayssi T Abstract Recent metabolomics studies of Rheumatoid Arthritis (RA) reported few metabolites that were associated with the disease, either due to small cohort sizes or limited coverage of metabolic pathways. Our objective is to identify metabolites associated with RA and its cofounders using a new untargeted metabolomics platform. Moreover, to investigate the pathomechanism of RA by identifying correlations between RA-associated metabolites. 132 RA patients and 104 controls were analyzed for 927 metabolites. Metabolites were tested for association with RA using linear regression. OPLS-DA was used to discriminate RA patients from controls. Gaussian Graphical Models (GGMs) were used to identify correlated metabolites. 32 metabolites are identified as significantly (Bonferroni) associated with RA, including the previously reported metabolites as DHEAS, cortisol and androstenedione and extending that to a larger set of metabolites in the steroid pathway. RA classification using metabolic profiles shows a sensitivity of 91% and specificity of 88%. Steroid levels show variation among the RA patients according to the corticosteroid treatment; lowest in those taking the treatment at the time of the study, higher in those who never took the treatment, and highest in those who took it in the past. Finally, the GGM reflects metabolite relations from the steroidogenesis pathway. PMID: 28831053 [PubMed - in process]

Related Articles Automated assembly of species metabolomes through data submission into a public repository. Gigascience. 2017 Aug 01;6(8):1-4 Authors: Salek RM, Conesa P, Cochrane K, Haug K, Williams M, Kale N, Moreno P, Jayaseelan KV, Macias JR, Nainala VC, Hall RD, Reed LK, Viant MR, O'Donovan C, Steinbeck C Abstract Following similar global efforts to exchange genomic and other biomedical data, global databases in metabolomics have now been established. MetaboLights, the first general purpose, publically available, cross-species, cross-application database in metabolomics, has become the fastest growing data repository at the European Bioinformatics Institute in terms of data volume. Here we present the automated assembly of species metabolomes in MetaboLights, a crucial reference for chemical biology, which is growing through user submissions. PMID: 28830114 [PubMed - in process]

Related Articles Diagnostic value of glutamate with 2-hydroxyglutarate in magnetic resonance spectroscopy for IDH1 mutant glioma. Neuro Oncol. 2016 Nov;18(11):1559-1568 Authors: Nagashima H, Tanaka K, Sasayama T, Irino Y, Sato N, Takeuchi Y, Kyotani K, Mukasa A, Mizukawa K, Sakata J, Yamamoto Y, Hosoda K, Itoh T, Sasaki R, Kohmura E Abstract BACKGROUND: Mutations in the isocitrate dehydrogenase 1 (IDH1) gene that are frequently observed in low-grade glioma are strongly associated with the accumulation of 2-hydroxyglutarate (2HG), which is a valuable diagnostic and prognostic biomarker of IDH1 mutant glioma. However, conventional MR spectroscopy (MRS)-based noninvasive detection of 2HG is challenging. In this study, we aimed to determine the additional value of other metabolites in predicting IDH1 mutations with conventional MRS. METHODS: Forty-seven patients with glioma underwent conventional single voxel short echo time MRS prior to surgery. A stereotactic navigation-guided operation was performed to resect tumor tissues in the center of the MRS voxel. MRS-based measurements of metabolites were validated with gas chromatography-mass spectrometry. We also conducted integrated analyses of glioma cell lines and clinical samples to examine the other metabolite levels and molecular findings in IDH1 mutant gliomas. RESULTS: A metabolomic analysis demonstrated higher levels of 2HG in IDH1 mutant glioma cells and surgical tissues. Interestingly, glutamate levels were significantly decreased in IDH1 mutant gliomas. Through an analysis of metabolic enzyme genes in glutamine pathways, it was shown that the expressions of branched-chain amino acid transaminase 1 were reduced and glutamate dehydrogenase levels were elevated in IDH1 mutant gliomas. Conventional MRS detection of glutamate and 2HG resulted in a high diagnostic accuracy (sensitivity 72%, specificity 96%) for IDH1 mutant glioma. CONCLUSIONS: IDH1 mutations alter glutamate metabolism. Combining glutamate levels optimizes the 2HG-based monitoring of IDH1 mutations via MRS and represents a reliable clinical application for diagnosing IDH1 mutant gliomas. PMID: 27154922 [PubMed - indexed for MEDLINE]

Association of pre-pregnancy body mass index with offspring metabolic profile: Analyses of 3 European prospective birth cohorts. PLoS Med. 2017 Aug;14(8):e1002376 Authors: Santos Ferreira DL, Williams DM, Kangas AJ, Soininen P, Ala-Korpela M, Smith GD, Jarvelin MR, Lawlor DA Abstract BACKGROUND: A high proportion of women start pregnancy overweight or obese. According to the developmental overnutrition hypothesis, this could lead offspring to have metabolic disruption throughout their lives and thus perpetuate the obesity epidemic across generations. Concerns about this hypothesis are influencing antenatal care. However, it is unknown whether maternal pregnancy adiposity is associated with long-term risk of adverse metabolic profiles in offspring, and if so, whether this association is causal, via intrauterine mechanisms, or explained by shared familial (genetic, lifestyle, socioeconomic) characteristics. We aimed to determine if associations between maternal body mass index (BMI) and offspring systemic cardio-metabolic profile are causal, via intrauterine mechanisms, or due to shared familial factors. METHODS AND FINDINGS: We used 1- and 2-stage individual participant data (IPD) meta-analysis, and a negative-control (paternal BMI) to examine the association between maternal pre-pregnancy BMI and offspring serum metabolome from 3 European birth cohorts (offspring age at blood collection: 16, 17, and 31 years). Circulating metabolic traits were quantified by high-throughput nuclear magnetic resonance metabolomics. Results from 1-stage IPD meta-analysis (N = 5327 to 5377 mother-father-offspring trios) showed that increasing maternal and paternal BMI was associated with an adverse cardio-metabolic profile in offspring. We observed strong positive associations with very-low-density lipoprotein (VLDL)-lipoproteins, VLDL-cholesterol (C), VLDL-triglycerides, VLDL-diameter, branched/aromatic amino acids, glycoprotein acetyls, and triglycerides, and strong negative associations with high-density lipoprotein (HDL), HDL-diameter, HDL-C, HDL2-C, and HDL3-C (all P < 0.003). Slightly stronger magnitudes of associations were present for maternal compared with paternal BMI across these associations; however, there was no strong statistical evidence for heterogeneity between them (all bootstrap P > 0.003, equivalent to P > 0.05 after accounting for multiple testing). Results were similar in each individual cohort, and in the 2-stage analysis. Offspring BMI showed similar patterns of cross-sectional association with metabolic profile as for parental pre-pregnancy BMI associations but with greater magnitudes. Adjustment of parental BMI-offspring metabolic traits associations for offspring BMI suggested the parental associations were largely due to the association of parental BMI with offspring BMI. Limitations of this study are that inferences cannot be drawn about the role of circulating maternal fetal fuels (i.e., glucose, lipids, fatty acids, and amino acids) on later offspring metabolic profile. In addition, BMI may not reflect potential effects of maternal pregnancy fat distribution. CONCLUSION: Our findings suggest that maternal BMI-offspring metabolome associations are likely to be largely due to shared genetic or familial lifestyle confounding rather than to intrauterine mechanisms. PMID: 28829768 [PubMed - in process]

Precision Nutrition: A Review of Personalized Nutritional Approaches for the Prevention and Management of Metabolic Syndrome. Nutrients. 2017 Aug 22;9(8): Authors: de Toro-Martín J, Arsenault BJ, Després JP, Vohl MC Abstract The translation of the growing increase of findings emerging from basic nutritional science into meaningful and clinically relevant dietary advices represents nowadays one of the main challenges of clinical nutrition. From nutrigenomics to deep phenotyping, many factors need to be taken into account in designing personalized and unbiased nutritional solutions for individuals or population sub-groups. Likewise, a concerted effort among basic, clinical scientists and health professionals will be needed to establish a comprehensive framework allowing the implementation of these new findings at the population level. In a world characterized by an overwhelming increase in the prevalence of obesity and associated metabolic disturbances, such as type 2 diabetes and cardiovascular diseases, tailored nutrition prescription represents a promising approach for both the prevention and management of metabolic syndrome. This review aims to discuss recent works in the field of precision nutrition analyzing most relevant aspects affecting an individual response to lifestyle/nutritional interventions. Latest advances in the analysis and monitoring of dietary habits, food behaviors, physical activity/exercise and deep phenotyping will be discussed, as well as the relevance of novel applications of nutrigenomics, metabolomics and microbiota profiling. Recent findings in the development of precision nutrition are highlighted. Finally, results from published studies providing examples of new avenues to successfully implement innovative precision nutrition approaches will be reviewed. PMID: 28829397 [PubMed - in process]

Extracellular Microbial Metabolomics: The State of the Art. Metabolites. 2017 Aug 22;7(3): Authors: Pinu FR, Villas-Boas SG Abstract Microorganisms produce and secrete many primary and secondary metabolites to the surrounding environment during their growth. Therefore, extracellular metabolites provide important information about the changes in microbial metabolism due to different environmental cues. The determination of these metabolites is also comparatively easier than the extraction and analysis of intracellular metabolites as there is no need for cell rupture. Many analytical methods are already available and have been used for the analysis of extracellular metabolites from microorganisms over the last two decades. Here, we review the applications and benefits of extracellular metabolite analysis. We also discuss different sample preparation protocols available in the literature for both types (e.g., metabolites in solution and in gas) of extracellular microbial metabolites. Lastly, we evaluate the authenticity of using extracellular metabolomics data in the metabolic modelling of different industrially important microorganisms. PMID: 28829385 [PubMed]

Related Articles Metabolomics reveals distinct neurochemical profiles associated with stress resilience. Neurobiol Stress. 2017 Dec;7:103-112 Authors: Dulka BN, Bourdon AK, Clinard CT, Muvvala MBK, Campagna SR, Cooper MA Abstract Acute social defeat represents a naturalistic form of conditioned fear and is an excellent model in which to investigate the biological basis of stress resilience. While there is growing interest in identifying biomarkers of stress resilience, until recently, it has not been feasible to associate levels of large numbers of neurochemicals and metabolites to stress-related phenotypes. The objective of the present study was to use an untargeted metabolomics approach to identify known and unknown neurochemicals in select brain regions that distinguish susceptible and resistant individuals in two rodent models of acute social defeat. In the first experiment, male mice were first phenotyped as resistant or susceptible. Then, mice were subjected to acute social defeat, and tissues were immediately collected from the ventromedial prefrontal cortex (vmPFC), basolateral/central amygdala (BLA/CeA), nucleus accumbens (NAc), and dorsal hippocampus (dHPC). Ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS) was used for the detection of water-soluble neurochemicals. In the second experiment, male Syrian hamsters were paired in daily agonistic encounters for 2 weeks, during which they formed stable dominant-subordinate relationships. Then, 24 h after the last dominance encounter, animals were exposed to acute social defeat stress. Immediately after social defeat, tissue was collected from the vmPFC, BLA/CeA, NAc, and dHPC for analysis using UPLC-HRMS. Although no single biomarker characterized stress-related phenotypes in both species, commonalities were found. For instance, in both model systems, animals resistant to social defeat stress also show increased concentration of molecules to protect against oxidative stress in the NAc and vmPFC. Additionally, in both mice and hamsters, unidentified spectral features were preliminarily annotated as potential targets for future experiments. Overall, these findings suggest that a metabolomics approach can identify functional groups of neurochemicals that may serve as novel targets for the diagnosis, treatment, or prevention of stress-related mental illness. PMID: 28828396 [PubMed]

Related Articles Prediction of Intravenous Busulfan Clearance by Endogenous Plasma Biomarkers Using Global Pharmacometabolomics. Metabolomics. 2016 Oct;12(10): Authors: Lin YS, Kerr SJ, Randolph T, Shireman LM, Senn T, McCune JS Abstract INTRODUCTION: High-dose busulfan (busulfan) is an integral part of the majority of hematopoietic cell transplantation conditioning regimens. Intravenous (IV) busulfan doses are personalized using pharmacokinetics (PK)-based dosing where the patient's IV busulfan clearance is calculated after the first dose and is used to personalize subsequent doses to a target plasma exposure. PK-guided dosing has improved patient outcomes and is clinically accepted but highly resource intensive. OBJECTIVE: We sought to discover endogenous plasma biomarkers predictive of IV busulfan clearance using a global pharmacometabolomics-based approach. METHODS: Using LC-QTOF, we analyzed 59 (discovery) and 88 (validation) plasma samples obtained before IV busulfan administration. RESULTS: In the discovery dataset, we evaluated the association of the relative abundance of 1885 ions with IV busulfan clearance and found 21 ions that were associated with IV busulfan clearance tertiles (r(2) ≥ 0.3). Identified compounds were deoxycholic acid and/or chenodeoxycholic acid, and linoleic acid. We used these 21 ions to develop a parsimonious seven-ion linear predictive model that accurately predicted IV busulfan clearance in 93% (discovery) and 78% (validation) of samples. CONCLUSION: IV busulfan clearance was significantly correlated with the relative abundance of 21 ions, seven of which were included in a predictive model that accurately predicted IV busulfan clearance in the majority of the validation samples. These results reinforce the potential of pharmacometabolomics as a critical tool in personalized medicine, with the potential to improve the personalized dosing of drugs with a narrow therapeutic index such as busulfan. PMID: 28827982 [PubMed]

Related Articles Crosstalk between the tricarboxylic acid cycle and peptidoglycan synthesis in Caulobacter crescentus through the homeostatic control of α-ketoglutarate. PLoS Genet. 2017 Aug 21;13(8):e1006978 Authors: Irnov I, Wang Z, Jannetty ND, Bustamante JA, Rhee KY, Jacobs-Wagner C Abstract To achieve robust replication, bacteria must integrate cellular metabolism and cell wall growth. While these two processes have been well characterized, the nature and extent of cross-regulation between them is not well understood. Here, using classical genetics, CRISPRi, metabolomics, transcriptomics and chemical complementation approaches, we show that a loss of the master regulator Hfq in Caulobacter crescentus alters central metabolism and results in cell shape defects in a nutrient-dependent manner. We demonstrate that the cell morphology phenotype in the hfq deletion mutant is attributable to a disruption of α-ketoglutarate (KG) homeostasis. In addition to serving as a key intermediate of the tricarboxylic acid (TCA) cycle, KG is a by-product of an enzymatic reaction required for the synthesis of peptidoglycan, a major component of the bacterial cell wall. Accumulation of KG in the hfq deletion mutant interferes with peptidoglycan synthesis, resulting in cell morphology defects and increased susceptibility to peptidoglycan-targeting antibiotics. This work thus reveals a direct crosstalk between the TCA cycle and cell wall morphogenesis. This crosstalk highlights the importance of metabolic homeostasis in not only ensuring adequate availability of biosynthetic precursors, but also in preventing interference with cellular processes in which these intermediates arise as by-products. PMID: 28827812 [PubMed - as supplied by publisher]

Related Articles Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation. Sci Rep. 2017 Aug 21;7(1):8938 Authors: Tian J, Zhu J, Yi Y, Li C, Zhang Y, Zhao Y, Pan C, Xiang S, Li X, Li G, Newman JW, Feng X, Liu J, Han J, Wang L, Gao Y, La Frano MR, Liang A Abstract Fructus Gardenia (FG), containing the major active constituent Geniposide, is widely used in China for medicinal purposes. Currently, clinical reports of FG toxicity have not been published, however, animal studies have shown FG or Geniposide can cause hepatotoxicity in rats. We investigated Geniposide-induced hepatic injury in male Sprague-Dawley rats after 3-day intragastric administration of 100 mg/kg or 300 mg/kg Geniposide. Changes in hepatic histomorphology, serum liver enzyme, serum and hepatic bile acid profiles, and hepatic bile acid synthesis and transportation gene expression were measured. The 300 mg/kg Geniposide caused liver injury evidenced by pathological changes and increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamytransferase (γ-GT). While liver, but not sera, total bile acids (TBAs) were increased 75% by this dose, dominated by increases in taurine-conjugated bile acids (t-CBAs). The 300 mg/kg Geniposide also down-regulated expression of Farnesoid X receptor (FXR), small heterodimer partner (SHP) and bile salt export pump (BSEP). In conclusion, 300 mg/kg Geniposide can induce liver injury with associated changes in bile acid regulating genes, leading to an accumulation of taurine conjugates in the rat liver. Taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA) as well as tauro-α-muricholic acid (T-α-MCA) are potential markers for Geniposide-induced hepatic damage. PMID: 28827769 [PubMed - in process]

Related Articles Arl8b is required for lysosomal degradation of maternal proteins in the visceral yolk sac endoderm of mouse embryos. J Cell Sci. 2017 Aug 21;: Authors: Oka M, Hashimoto K, Yamaguchi Y, Saitoh SI, Sugiura Y, Motoi Y, Honda K, Kikko Y, Ohata S, Suematsu M, Miura M, Miyake K, Katada T, Kontani K Abstract The small GTPase Arl8b localizes primarily to lysosomes and is involved in lysosomal motility and fusion. Here, we show that Arl8b is required for lysosomal degradation of maternal proteins in the visceral yolk sac endoderm (VYSE), an apical cell layer of the visceral yolk sac, of mouse embryos. The VYSE actively takes up maternal materials from uterine fluid and degrades them in lysosomes to provide breakdown products to the embryo as energy sources. Arl8b gene-trap mice (Arl8b(-/-) ) displayed decreased early embryo body size. The Arl8b(-/-) VYSE exhibited defective endocytic trafficking to the lysosome and accumulation of maternal proteins such as albumin and immunoglobulin G in late endocytic organelles. Furthermore, Transthyretin-Cre;Arl8b(flox/flox) mice in which Arl8b was ablated specifically in the VYSE also showed decreased embryo body size, defects in trafficking to the lysosome, and reduction of the free amino acid level in the embryos. Taken together, these results suggest that Arl8b mediates lysosomal degradation of maternal proteins in the VYSE, thereby contributing to mouse embryonic development. PMID: 28827407 [PubMed - as supplied by publisher]

Related Articles Exploring Metabolism In Vivo Using Endogenous (11)C Metabolic Tracers. Semin Nucl Med. 2017 Sep;47(5):461-473 Authors: Neumann K, Flavell R, Wilson DM Abstract Cancer and other diseases are increasingly understood in terms of their metabolic disturbances. This thinking has revolutionized the field of ex vivo metabolomics and motivated new approaches to detect metabolites in living systems, including proton magnetic resonance spectroscopy ((1)H-MRS), hyperpolarized (13)C MRS, and PET. For PET, imaging abnormal metabolism in vivo is hardly new. Positron-labeled small-molecule metabolites have been used for decades in humans, including (18)F-FDG, which is used frequently to detect upregulated glycolysis in tumors. Many current (18)F metabolic tracers including (18)F-FDG have evolved from their (11)C counterparts, chemically identical to endogenous substrates and thus approximating intrinsic biochemical pathways. This mimicry has stimulated the development of new radiochemical methods to incorporate (11)C and inspired the synthesis of a large number of (11)C endogenous radiotracers. This is in spite of the 20-minute half-life of (11)C, which generally limits its use in patients to centers with an on-site cyclotron. Innovation in (11)C chemistry has persisted in the face of this limitation, because (1) the radiochemists involved are inspired, (2) the methods of (11)C incorporation are diverse, and (3) (11)C compounds often show more predictable in vivo behavior, thus representing an important first step in the validation of new tracer concepts. In this mini-review we will discuss some of the general motivations behind PET tracers, rationales for the use of (11)C, and some of the special challenges encountered in the synthesis of (11)C endogenous compounds. Most importantly, we will try to highlight the exceptional creativity used in early (11)C tracer syntheses, which used enzyme-catalyzed and other "green" methods before these concepts were commonplace. PMID: 28826521 [PubMed - in process]

Related Articles Quantitative profiling of 19 bile acids in rat plasma, liver, bile and different intestinal section contents to investigate bile acid homeostasis and the application of temporal variation of endogenous bile acids. J Steroid Biochem Mol Biol. 2017 Sep;172:69-78 Authors: Yang T, Shu T, Liu G, Mei H, Zhu X, Huang X, Zhang L, Jiang Z Abstract Bile acid homeostasis is maintained by liver synthesis, bile duct secretion, microbial metabolism and intestinal reabsorption into the blood. When drug insults result in liver damage, the variances of bile acids (BAs) are related to the physiological status of the liver. Here, we established a method to simultaneously quantify 19 BAs in rat plasma, liver, bile and different intestinal section contents (duodenum, jejunum, ileum, cecum and colon) using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) to reveal the pattern of bile acid homeostasis in the enterohepatic circulation of bile acids in physiological situations. Dynamic changes in bile acid composition appeared throughout the enterohepatic circulation of the BAs; taurine- and glycine-conjugated BAs and free BAs had different dynamic homeostasis levels in the circulatory system. cholic acid (CA), beta-muricholic acid (beta-MCA), lithocholic acid (LCA), glycocholic acid (GCA) and taurocholic acid (TCA) greatly fluctuated in the bile acid pool under physiological conditions. Taurine- and glycine-conjugated bile acids constituted more than 90% in the bile and liver, whereas GCA and TCA accounted for more than half of the total bile acids and the secretion of bile mainly via conjugating with taurine. While over 80% of BAs in plasma were unconjugated bile acids, CA and HDCA were the most abundant elements. Unconjugated bile acids constituted more than 90% in the intestine, and CA, beta-MCA and HDCA were the top three bile acids in the duodenum, jejunum and ileum content, but LCA and HDCA were highest in the cecum and colon content. As the main secondary bile acid converted by microflora in the intestine, LCA was enriched in the cecum and DCA mostly in the colon. As endogenous substances, the concentrations of plasma BAs were closely related to time rhythm and diet. In conclusion, analyzing detailed BA profiles in the enterohepatic circulation of bile acids in a single run is possible using LC-MS/MS. Based on the physiological characteristics of the metabolic profiling of 19 BAs in the total bile acid pool and the time rhythm variation of the endogenous bile acids, this study provided a new valuable method and theoretical basis for the clinical research of bile acid homeostasis. PMID: 28583875 [PubMed - indexed for MEDLINE]

Related Articles Diversity and association of phenotypic and metabolomic traits in the close model grasses Brachypodium distachyon, B. stacei and B. hybridum. Ann Bot. 2017 Mar 01;119(4):545-561 Authors: López-Álvarez D, Zubair H, Beckmann M, Draper J, Catalán P Abstract Background and Aims: Morphological traits in combination with metabolite fingerprinting were used to investigate inter- and intraspecies diversity within the model annual grasses Brachypodium distachyon, Brachypodium stacei and Brachypodium hybridum . Methods: Phenotypic variation of 15 morphological characters and 2219 nominal mass ( m / z ) signals generated using flow infusion electrospray ionization-mass spectrometry (FIE-MS) were evaluated in individuals from a total of 174 wild populations and six inbred lines, and 12 lines, of the three species, respectively. Basic statistics and multivariate principal component analysis and discriminant analysis were used to differentiate inter- and intraspecific variability of the two types of variable, and their association was assayed with the rcorr function. Key Results: Basic statistics and analysis of variance detected eight phenotypic characters [(stomata) leaf guard cell length, pollen grain length, (plant) height, second leaf width, inflorescence length, number of spikelets per inflorescence, lemma length, awn length] and 434 tentatively annotated metabolite signals that significantly discriminated the three species. Three phenotypic traits (pollen grain length, spikelet length, number of flowers per inflorescence) might be genetically fixed. The three species showed different metabolomic profiles. Discriminant analysis significantly discriminated the three taxa with both morphometric and metabolome traits and the intraspecific phenotypic diversity within B. distachyon and B. stacei . The populations of B. hybridum were considerably less differentiated. Conclusions: Highly explanatory metabolite signals together with morphological characters revealed concordant patterns of differentiation of the three taxa. Intraspecific phenotypic diversity was observed between northern and southern Iberian populations of B. distachyon and between eastern Mediterranean/south-western Asian and western Mediterranean populations of B. stacei . Significant association was found for pollen grain length and lemma length and ten and six metabolomic signals, respectively. These results would guide the selection of new germplasm lines of the three model grasses in ongoing genome-wide association studies. PMID: 28040672 [PubMed - indexed for MEDLINE]

Related Articles MicroRNA858 Is a Potential Regulator of Phenylpropanoid Pathway and Plant Development. Plant Physiol. 2016 Jun;171(2):944-59 Authors: Sharma D, Tiwari M, Pandey A, Bhatia C, Sharma A, Trivedi PK Abstract MicroRNAs (miRNAs) are endogenous, noncoding small RNAs that function as critical regulators of gene expression. In plants, miRNAs have shown their potential as regulators of growth, development, signal transduction, and stress tolerance. Although the miRNA-mediated regulation of several processes is known, the involvement of miRNAs in regulating secondary plant product biosynthesis is poorly understood. In this study, we functionally characterized Arabidopsis (Arabidopsis thaliana) miR858a, which putatively targets R2R3-MYB transcription factors involved in flavonoid biosynthesis. Overexpression of miR858a in Arabidopsis led to the down-regulation of several MYB transcription factors regulating flavonoid biosynthesis. In contrast to the robust growth and early flowering of miR858OX plants, reduction of plant growth and delayed flowering were observed in Arabidopsis transgenic lines expressing an artificial miRNA target mimic (MIM858). Genome-wide expression analysis using transgenic lines suggested that miR858a targets a number of regulatory factors that modulate the expression of downstream genes involved in plant development and hormonal and stress responses. Furthermore, higher expression of MYBs in MIM858 lines leads to redirection of the metabolic flux towards the synthesis of flavonoids at the cost of lignin synthesis. Altogether, our study has established the potential role of light-regulated miR858a in flavonoid biosynthesis and plant growth and development. PMID: 27208307 [PubMed - indexed for MEDLINE]

Related Articles Volatile organic compounds in breath as markers for irritable bowel syndrome: a metabolomic approach. Aliment Pharmacol Ther. 2016 Jul;44(1):45-56 Authors: Baranska A, Mujagic Z, Smolinska A, Dallinga JW, Jonkers DM, Tigchelaar EF, Dekens J, Zhernakova A, Ludwig T, Masclee AA, Wijmenga C, van Schooten FJ Abstract BACKGROUND: The diagnosis of irritable bowel syndrome (IBS) is challenging because of its heterogeneity and multifactorial pathophysiology. No reliable biomarkers of IBS have been identified so far. AIMS: In a case-control study, using a novel application of breath analysis to distinguish IBS patients from healthy controls based on the analysis of volatile organic compounds (VOCs). Subsequently, the diagnostic VOC-biomarker set was correlated with self-reported gastrointestinal (GI) symptoms of subjects of the Maastricht IBS clinical cohort and of a general population cohort, LifeLines DEEP. METHODS: Breath samples were collected from 170 IBS patients and 153 healthy controls in the clinical cohort and from 1307 participants in general population cohort. Multivariate statistics were used to identify the most discriminatory set of VOCs in the clinical cohort, and to find associations between VOCs and GI symptoms in both cohorts. RESULTS: A set of 16 VOCs correctly predicted 89.4% of the IBS patients and 73.3% of the healthy controls (AUC = 0.83). The VOC-biomarker set correlated moderately with a set of GI symptoms in the clinical (r = 0.55, P = 0.0003) and general population cohorts (r = 0.54, P = 0.0004). A Kruskal-Wallis test showed no influence from possible confounding factors in distinguishing IBS patients from healthy controls. CONCLUSIONS: A set of 16 breath-based biomarkers that distinguishes IBS patients from healthy controls was identified. The VOC-biomarker set correlated significantly with GI symptoms in two independent cohorts. We demonstrate the potential use of breath analysis in the diagnosis and monitoring of IBS, and a possible application of VOC analyses in a general population cohort. PMID: 27136066 [PubMed - indexed for MEDLINE]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/08/22PubMed 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.

Comparative study of single/combination use of Huang-Lian-Jie-Du decoction and berberine on their protection on sepsis induced acute liver injury by NMR metabolic profiling. J Pharm Biomed Anal. 2017 Aug 01;145:794-804 Authors: Lv Y, Wang J, Xu D, Liao S, Li P, Zhang Q, Yang M, Kong L Abstract Sepsis is a serious clinical disease with a high mortality rate all around the world. Liver organ dysfunction is an important sign for the severity and outcome of sepsis in patients. In this study, (1)H NMR-based metabolomics approach and biochemical assays were applied to investigate the metabolic profiling for cecal ligation and puncture (CLP) induced acute liver injury, the therapeutical effect of single/combination use of Huang-Lian-Jie-Du decoction (HLJDD) and berberine, and the interaction of them. Metabolomics analysis revealed significant perturbations in livers of septic rats, which could be ameliorated by HLJDD, berberine and their combination treatment. Berberine could better rectified glycolysis and nucleic acid metabolism in the liver. HLJDD had exceptional better anti-inflammatory, antibacterial and antioxidative effects than berberine. The interaction of berberine and HLJDD could further strengthen the anti-inflammation and anti-oxidation, but with poor effect on amino acids metabolism. These findings highlighted the feasibility of the integrated NMR based metabolomics approach to understand the pathogenesis of diseases, the action mechanisms of therapy and the herb-drug interaction. PMID: 28822346 [PubMed - as supplied by publisher]

[Metabolic fingerprint analysis of RAW264.7 inflammatory cell model by using UPLC-Q-TOF/MS]. Zhongguo Zhong Yao Za Zhi. 2017 Jun;42(12):2373-2379 Authors: Gao SS, Guo HQ, Zhang ZK, Bai GC, Gao XY, Ma CH Abstract In order to reveal the properties of polar metabolome in inflammatory cells, we selected LPS-induced RAW264.7 inflammatory cell models as the carrier for the research of metabolic fingerprint analysis. In this study, an ultra performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics protocol was optimized for the extraction of polar metabolites from RAW264.7 cell line. Then orthogonal partial least squares discriminant analysis (OPLS-DA) was used to process the metabolic data, and finally, a total of 17 metabolites were selected and identified. The results showed that MeOH-CHCl3-H2O (8∶1∶1) was chosen as the optimal extraction solvent to achieve higher number of chromatographic peaks, with the best relative extraction efficiency and stability. Comparing with the normal cells, the inflammatory cells presented an abnormal metabolism in protein, carbohydrate, nucleotide and phospholipids. In this study, a UPLC-Q-TOF/MS-based metabolomics protocol for the polar metabolites from RAW264.7 cell line was developed, which may provide important information for the study of mechanism of inflammation and the anti-inflammatory drugs. PMID: 28822196 [PubMed - in process]