PubMed

Related Articles A pilot study identifying a potential plasma biomarker for determining EGFR mutations in exons 19 or 21 in lung cancer patients. Mol Med Rep. 2017 Apr 28;: Authors: Pamungkas AD, Medriano CA, Sim E, Lee S, Park YH Abstract The most common type of lung cancer is non‑small cell lung cancer (NSCLC), which is frequently characterized by a mutation in the epidermal growth factor receptor (EGFR). Determining the presence of an EGFR mutation in lung cancer is important, as it determines the type of treatment that a patients will receive. Therefore, the aim of the present study was to apply high‑resolution metabolomics (HRM) using liquid chromatography‑mass spectrometry to identify significant compounds in human plasma samples obtained from South Korean NSCLC patients, as potential biomarkers for providing early detection and diagnosis of minimally‑invasive NSCLC. The metabolic differences between lung cancer patients without EGFR mutations were compared with patients harboring EGFR mutations. Univariate analysis was performed, with a false discovery rate of q=0.05, in order to identify significant metabolites between the two groups. In addition, hierarchical clustering analysis was performed to discriminate between the metabolic profiles of the two groups. Furthermore, the significant metabolites were identified and mapped using Mummichog software, in order to generate a potential metabolic network model. Using metabolome‑wide association studies, metabolic alterations were identified. Linoleic acid [303.23 m/z, (M+Na)+], 5‑methyl tetrahydrofolate [231.10 m/z, (M+2H)+] and N‑succinyl‑L‑glutamate‑5 semialdehyde [254.06 m/z, (M+Na)+], were observed to be elevated in patients harboring EGFR mutations, whereas tetradecanoyl carnitine [394.29 m/z, (M+Na)+] was observed to be reduced. This suggests that these compounds may be affected by the EGFR mutation. In conclusion, the present study identified four potential biomarkers in patients with EGFR mutations, using HRM combined with pathway analysis. These results may facilitate the development of novel diagnostic tools for EGFR mutation detection in patients with lung cancer. PMID: 28487968 [PubMed - as supplied by publisher]

Related Articles New tools and approaches to newborn screening: ready to open Pandora's box? Cold Spring Harb Mol Case Stud. 2017 May;3(3):a001842 Authors: Ficicioglu C Abstract The landscape of newborn screening (NBS) is changing as new tools are developed. We must acknowledge that NBS is a very important and extraordinarily positive initiative especially for rare and serious inherited disorders; however, lessons learned from current NBS should guide the future of NBS as we enter the era of "omics" that will expand NBS for many other genetic disorders. In this article, I will first discuss new tools such as genomics and metabolomics for NBS. I will then turn to assessing how best to take advantage of new technical developments while considering the best interests of patients and the success of newborn screening. PMID: 28487886 [PubMed - in process]

Related Articles Finger Millet: A "Certain" Crop for an "Uncertain" Future and a Solution to Food Insecurity and Hidden Hunger under Stressful Environments. Front Plant Sci. 2017;8:643 Authors: Gupta SM, Arora S, Mirza N, Pande A, Lata C, Puranik S, Kumar J, Kumar A Abstract Crop growth and productivity has largely been vulnerable to various abiotic and biotic stresses that are only set to be compounded due to global climate change. Therefore developing improved varieties and designing newer approaches for crop improvement against stress tolerance have become a priority now-a-days. However, most of the crop improvement strategies are directed toward staple cereals such as rice, wheat, maize etc., whereas attention on minor cereals such as finger millet [Eleusine coracana (L.) Gaertn.] lags far behind. It is an important staple in several semi-arid and tropical regions of the world with excellent nutraceutical properties as well as ensuring food security in these areas even during harsh environment. This review highlights the importance of finger millet as a model nutraceutical crop. Progress and prospects in genetic manipulation for the development of abiotic and biotic stress tolerant varieties is also discussed. Although limited studies have been conducted for genetic improvement of finger millets, its nutritional significance in providing minerals, calories and protein makes it an ideal model for nutrition-agriculture research. Therefore, improved genetic manipulation of finger millets for resistance to both abiotic and biotic stresses, as well as for enhancing nutrient content will be very effective in millet improvement. Key message: Apart from the excellent nutraceutical value of finger millet, its ability to tolerate various abiotic stresses and resist pathogens make it an excellent model for exploring vast genetic and genomic potential of this crop, which provide us a wide choice for developing strategies for making climate resilient staple crops. PMID: 28487720 [PubMed - in process]

Related Articles A Combined Comparative Transcriptomic, Metabolomic, and Anatomical Analyses of Two Key Domestication Traits: Pod Dehiscence and Seed Dormancy in Pea (Pisum sp.). Front Plant Sci. 2017;8:542 Authors: Hradilová I, Trněný O, Válková M, Cechová M, Janská A, Prokešová L, Aamir K, Krezdorn N, Rotter B, Winter P, Varshney RK, Soukup A, Bednář P, Hanáček P, Smýkal P Abstract The origin of the agriculture was one of the turning points in human history, and a central part of this was the evolution of new plant forms, domesticated crops. Seed dispersal and germination are two key traits which have been selected to facilitate cultivation and harvesting of crops. The objective of this study was to analyze anatomical structure of seed coat and pod, identify metabolic compounds associated with water-impermeable seed coat and differentially expressed genes involved in pea seed dormancy and pod dehiscence. Comparative anatomical, metabolomics, and transcriptomic analyses were carried out on wild dormant, dehiscent Pisum elatius (JI64, VIR320) and cultivated, indehiscent Pisum sativum non-dormant (JI92, Cameor) and recombinant inbred lines (RILs). Considerable differences were found in texture of testa surface, length of macrosclereids, and seed coat thickness. Histochemical and biochemical analyses indicated genotype related variation in composition and heterogeneity of seed coat cell walls within macrosclereids. Liquid chromatography-electrospray ionization/mass spectrometry and Laser desorption/ionization-mass spectrometry of separated seed coats revealed significantly higher contents of proanthocyanidins (dimer and trimer of gallocatechin), quercetin, and myricetin rhamnosides and hydroxylated fatty acids in dormant compared to non-dormant genotypes. Bulk Segregant Analysis coupled to high throughput RNA sequencing resulted in identification of 770 and 148 differentially expressed genes between dormant and non-dormant seeds or dehiscent and indehiscent pods, respectively. The expression of 14 selected dormancy-related genes was studied by qRT-PCR. Of these, expression pattern of four genes: porin (MACE-S082), peroxisomal membrane PEX14-like protein (MACE-S108), 4-coumarate CoA ligase (MACE-S131), and UDP-glucosyl transferase (MACE-S139) was in agreement in all four genotypes with Massive analysis of cDNA Ends (MACE) data. In case of pod dehiscence, the analysis of two candidate genes (SHATTERING and SHATTERPROOF) and three out of 20 MACE identified genes (MACE-P004, MACE-P013, MACE-P015) showed down-expression in dorsal and ventral pod suture of indehiscent genotypes. Moreover, MACE-P015, the homolog of peptidoglycan-binding domain or proline-rich extensin-like protein mapped correctly to predicted Dpo1 locus on PsLGIII. This integrated analysis of the seed coat in wild and cultivated pea provides new insight as well as raises new questions associated with domestication and seed dormancy and pod dehiscence. PMID: 28487704 [PubMed - in process]

Related Articles Urinary metabolomics analysis identifies key biomarkers of different stages of nonalcoholic fatty liver disease. World J Gastroenterol. 2017 Apr 21;23(15):2771-2784 Authors: Dong S, Zhan ZY, Cao HY, Wu C, Bian YQ, Li JY, Cheng GH, Liu P, Sun MY Abstract AIM: To identify a panel of biomarkers that can distinguish between non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and explore molecular mechanism involved in the process of developing NASH from NAFLD. METHODS: Biomarkers may differ during stages of NAFLD. Urine and blood were obtained from non-diabetic subjects with NAFLD and steatosis, with normal liver function (n = 33), from patients with NASH, with abnormal liver function (n = 45), and from healthy age and sex-matched controls (n = 30). Samples were subjected to metabolomic analysis to identify potential non-invasive biomarkers. Differences in urinary metabolic profiles were analyzed using liquid chromatography tandem mass spectrometry with principal component analysis and partial least squares-discriminate analysis. RESULTS: Compared with NAFLD patients, patients with NASH had abnormal liver function and high serum lipid concentrations. Urinary metabonomics found differences in 31 metabolites between these two groups, including differences in nucleic acids and amino acids. Pathway analysis based on overlapping metabolites showed that pathways of energy and amino acid metabolism, as well as the pentose phosphate pathway, were closely associated with pathological processes in NAFLD and NASH. CONCLUSION: These findings suggested that a panel of biomarkers could distinguish between NAFLD and NASH, and could help to determine the molecular mechanism involved in the process of developing NASH from NAFLD. Urinary biomarkers may be diagnostic in these patients and could be used to assess responses to therapeutic interventions. PMID: 28487615 [PubMed - in process]

Related Articles Changes in human hepatic metabolism in steatosis and cirrhosis. World J Gastroenterol. 2017 Apr 21;23(15):2685-2695 Authors: Schofield Z, Reed MA, Newsome PN, Adams DH, Günther UL, Lalor PF Abstract AIM: To understand the underlying metabolic changes in human liver disease we have applied nuclear magnetic resonance (NMR) metabolomics analysis to human liver tissue. METHODS: We have carried out pilot study using (1)H-NMR to derive metabolomic signatures from human liver from patients with steatosis, nonalcoholic steatohepatitis (NASH) or alcohol-related liver damage (ARLD) to identify species that can predict outcome and discriminate between alcohol and metabolic-induced liver injuries. RESULTS: Changes in branched chain amino acid homeostasis, tricarboxylic acid cycle and purine biosynthesis intermediates along with betaine were associated with the development of cirrhosis in both ARLD and nonalcoholic fatty liver disease. Species such as propylene glycol and as yet unidentified moieties that allowed discrimination between NASH and ARLD samples were also detected using our approach. CONCLUSION: Our high throughput, non-destructive technique for multiple analyte quantification in human liver specimens has potential for identification of biomarkers with prognostic and diagnostic significance. PMID: 28487605 [PubMed - in process]

Related Articles Dioxin-induced increase in leukotriene B4 biosynthesis through the aryl hydrocarbon receptor and its relevance to hepatotoxicity owing to neutrophil infiltration. J Biol Chem. 2017 May 09;: Authors: Takeda T, Komiya Y, Koga T, Ishida T, Ishii Y, Kikuta Y, Nakaya M, Kurose H, Yokomizo T, Shimizu T, Uchi H, Furue M, Yamada H Abstract Dioxin and related chemicals alter the expression of a number of genes by activating the aryl hydrocarbon receptors (AHRs) to produce a variety of disorders including hepatotoxicity. However, it remains largely unknown how these changes in gene expression are linked to toxicity. To address this issue, we initially examined the effect of 2,3,7,8-tetrachrolodibenzo-p-dioxin (TCDD), a most toxic dioxin, on the hepatic and serum metabolome in male pubertal rats. The results obtained showed that TCDD causes many changes in the level of fatty acids, bile acids, amino acids and their metabolites. Among them, we discovered that TCDD increases the content of leukotriene (LT) B4, an inflammation-inducer due to the activation of leukocytes, in the liver of rats and mice. Further analyses suggested that an increase in LTB4 comes from a dual mechanism consisting of an induction of arachidonate lipoxygenase-5, a rate-limiting enzyme in LTB4 synthesis, and down-regulation of LTC4 synthase, an enzyme converting LTA4 to LTC4. The above changes require AHR activation, because the same was not observed in AHR-knockout rats. In agreement with LTB4 accumulation, TCDD caused the marked infiltration of neutrophils into the liver. However, deleting LTB4 receptors (BLT1) blocked this effect. A TCDD-produced increase in the mRNA expression of inflammatory markers including tumor-necrosis factor and hepatic damage was also suppressed in BLT1-null mice. A series of the above observations focusing on metabolomic changes provides novel evidence that TCDD accumulates LTB4 in the liver by an AHR-dependent induction of LTB4 biosynthesis to cause hepatotoxicity through neutrophil activation. PMID: 28487374 [PubMed - as supplied by publisher]

Related Articles Identification of potential diagnostic biomarkers of acute pancreatitis by serum metabolomic profiles. Pancreatology. 2017 May 03;: Authors: Xiao H, Huang JH, Zhang XW, Ahmed R, Xie QL, Li B, Zhu YM, Cai X, Peng QH, Qin YH, Huang HY, Wang W Abstract Acute pancreatitis (AP) is defined as an acute inflammation of pancreas that may cause damage to other tissues and organs depending upon the severity of symptoms. The diagnosis of AP is usually made by detection of raised circulating pancreatic enzyme levels, but there are occasional false positive and false negative diagnoses and such tests are often normal in delayed presentations. More accurate biomarkers would help in such situations. In this study, the global metabolites' changes of AP patients (APP) were profiled by using gas chromatography-mass spectrometry (GC-MS). Multivariate pattern recognition techniques were used to establish the classification models to distinguish APP from healthy participants (HP). Some significant metabolites including 3-hydroxybutyric acid, phosphoric acid, glycerol, citric acid, d-galactose, d-mannose, d-glucose, hexadecanoic acid and serotonin were selected as potential biomarkers for helping clinical diagnosis of AP. Furthermore, the metabolite changes in APP with severe and mild symptoms were also analyzed. Based on the selected biomarkers, some relevant pathways were also identified. Our results suggested that GC-MS based serum metabolomics method can be used in the clinical diagnosis of AP by profiling potential biomarkers. PMID: 28487129 [PubMed - as supplied by publisher]

Related Articles Design of strategies to study the metabolic profile of highly polar compounds in plasma by reversed-phase liquid chromatography-high resolution mass spectrometry. J Chromatogr A. 2017 Mar 24;1490:156-165 Authors: Sánchez-López E, Crego AL, Marina ML Abstract Amino acids and related compounds are paramount analytes which are involved in numerous metabolic pathways. Most of these compounds are unable to be retained on Liquid Chromatography with Reversed-Phase stationary phases due to their high hydrophilic character. An interesting strategy is to reduce their polarity through their derivatization with a labelling reagent, such as the commercially available 9-fluorenylmethyloxycarbonyl (FMOC) which forms stable complexes with primary and secondary amine moieties rapidly. Although some derivatization reagents have been employed in the study of metabolic profiles, as far as we know, FMOC has never been employed for this purpose. In this work, it is demonstrated that the use of RP-LCMS(TOF) using a C18 column and FMOC as labelling agent enables the determination of a larger number of hydrophilic compounds (proteinogenic amino acids, non-proteinogenic amino acids, and biogenic amines) when compared to the use of a fully-wettable pentafluorophenyl column in fully-aqueous conditions (gradient starting in 0% of organic solvent) and HILIC column, both without using compound derivatization. Different strategies for plasma protein elimination were also carefully evaluated. Results revealed that ultrafiltration (UF) offered a lower variability from sample to sample when compared to the protein precipitation (PP) method (from 2 to 12 times lower variability found in UF). Additionally, UF preserved a larger number of possible compounds when compared to the PP approach: 4631 unique molecular features with UF, 666 unique molecular features with PP. PMID: 28238323 [PubMed - indexed for MEDLINE]

44 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 2017/05/10PubMed 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.

Salinity affects metabolomic profiles of different trophic levels in a food chain. Sci Total Environ. 2017 May 02;599-600:198-206 Authors: Nam KH, Kim YJ, Moon YS, Pack IS, Kim CG Abstract Salinization is one of the most important abiotic stressors in an ecosystem. To examine how exposing a host plant to excess salt affects the consequent performance and metabolism of insects in a food chain, we determined the life history traits and the metabolite profiles in rice (Oryza sativa), the herbivore Sitobion avenae, and its predator Harmonia axyridis. When compared with performance under normal (non-stressed) conditions, exposing plants to 50mM NaCl significantly delayed the timing of development for S. avenae fed on rice and H. axyridis and also reduced the body mass of the latter. Our GC-MS-based analysis revealed clear differences in metabolite profiles between trophic levels or treatment conditions. Salinity apparently increased the levels of main components in rice, but decreased levels of major components in S. avenae and H. axyridis. In addition, 16 metabolites showed salinity-related contrasts in this trophic interaction for our rice-S. avenae-H. axyridis system. Salinity impeded the accumulation of metabolites, especially several sugars, amino acids, organic acids, and fatty acids in both insects, a response that was possibly associated with the negative impacts on their growth and reproduction under stress conditions. PMID: 28475913 [PubMed - as supplied by publisher]

DNA Damage in Stem Cells. Mol Cell. 2017 May 04;66(3):306-319 Authors: Vitale I, Manic G, De Maria R, Kroemer G, Galluzzi L Abstract Both embryonic and adult stem cells are endowed with a superior capacity to prevent the accumulation of genetic lesions, repair them, or avoid their propagation to daughter cells, which would be particularly detrimental to the whole organism. Inducible pluripotent stem cells also display a robust DNA damage response, but the stability of their genome is often conditioned by the mutational history of the cell population of origin, which constitutes an obstacle to clinical applications. Cancer stem cells are particularly tolerant to DNA damage and fail to undergo senescence or regulated cell death upon accumulation of genetic lesions. Such a resistance contributes to the genetic drift of evolving tumors as well as to their limited sensitivity to chemo- and radiotherapy. Here, we discuss the pathophysiological and therapeutic implications of the molecular pathways through which stem cells cope with DNA damage. PMID: 28475867 [PubMed - in process]

NMR-based metabolomic analysis for the effects of creatine supplementation on mouse myoblast cell line C2C12. Acta Biochim Biophys Sin (Shanghai). 2017 May 05;:1-11 Authors: Xu W, Lin D, Huang C Abstract Creatine (Cr) supplementation has drawn much attention from researchers owing to its widespread efficacy in sports, and more recently, in therapeutic fields. However, the underlying molecular mechanisms remain elusive. Here, we performed nuclear magnetic resonance-based metabolomic analysis to address the metabolic profile of aqueous extracts from the mouse myoblast cell line C2C12 exposed to 2 mM Cr for 24 h (the Cr-treated group). Results showed that Cr supplementation facilitated the proliferation of C2C12 myoblasts. Both pattern recognition and hierarchical cluster analyses demonstrated that the metabolic profiles of the Cr-treated and control groups were distinctly different. We identified 13 characteristic metabolites significantly responsible for the discrimination of metabolic profiles between the two groups, through orthogonal projection to latent structures discriminant analysis and independent samples t-test. We further verified the discrimination performances of these metabolites by conducting univariate receiver operating characteristic curve analysis. Compared with the control group, the Cr-treated group exhibited increased levels of Cr, phosphocreatine (PCr), glutathione (GSH), and glucose, but decreased levels of leucine, valine, isoleucine, phenylalanine, methionine, choline, O-phosphocholine, sn-glycero-3-phosphocholine, and glycerol. Our results demonstrated that Cr supplementation upregulated PCr and glucose, promoted trichloroacetic acid cycle anaplerotic flux and GSH-mediated antioxidant capacity, and stabilized lipid membranes through suppressing glycerophospholipid metabolism. Our work provides new clues to the molecular mechanisms underlying the pleiotropic effects of Cr in muscle cells. PMID: 28475656 [PubMed - as supplied by publisher]

Metabolic Dysregulation after Neutron Exposures Expected from an Improvised Nuclear Device. Radiat Res. 2017 May 05;: Authors: Laiakis EC, Wang YW, Young EF, Harken AD, Xu Y, Smilenov L, Garty GY, Brenner DJ, Fornace AJ Abstract The increased threat of terrorism across the globe has raised fears that certain groups will acquire and use radioactive materials to inflict maximum damage. In the event that an improvised nuclear device (IND) is detonated, a potentially large population of victims will require assessment for radiation exposure. While photons will contribute to a major portion of the dose, neutrons may be responsible for the severity of the biologic effects and cellular responses. We investigated differences in response between these two radiation types by using metabolomics and lipidomics to identify biomarkers in urine and blood of wild-type C57BL/6 male mice. Identification of metabolites was based on a 1 Gy dose of radiation. Compared to X rays, a neutron spectrum similar to that encountered in Hiroshima at 1-1.5 km from the epicenter induced a severe metabolic dysregulation, with perturbations in amino acid metabolism and fatty acid β-oxidation being the predominant ones. Urinary metabolites were able to discriminate between neutron and X rays on day 1 as well as day 7 postirradiation, while serum markers showed such discrimination only on day 1. Free fatty acids from omega-6 and omega-3 pathways were also decreased with 1 Gy of neutrons, implicating cell membrane dysfunction and impaired phospholipid metabolism, which should otherwise lead to release of those molecules in circulation. While a precise relative biological effectiveness value could not be calculated from this study, the results are consistent with other published studies showing higher levels of damage from neutrons, demonstrated here by increased metabolic dysregulation. Metabolomics can therefore aid in identifying global perturbations in blood and urine, and effectively distinguishing between neutron and photon exposures. PMID: 28475424 [PubMed - as supplied by publisher]

Identification of differential metabolic characteristics between tumor and normal tissue from colorectal cancer patients by gas chromatography-mass spectrometry. Biomed Chromatogr. 2017 May 05;: Authors: Ning W, Li H, Meng F, Cheng J, Song X, Zhang G, Wang W, Wu S, Fang J, Ma K, Yang J, Pei D, Dong F Abstract Colorectal cancer (CRC) is one of the most common human malignancies and encompasses cancers of the colon and rectum. Although the gold-standard colonoscopy screening method is effective in detecting CRC, this method is invasive and can result in severe complications for patients. The purpose of this study was to determine differences in metabolites between CRC and matched adjacent non-tumor tissues from CRC patients, to identify potential biomarkers that may be informative and developed screening methods. Metabolomic analysis was performed on clinically localized CRC tissue and matched adjacent non-tumor tissue from twenty CRC patients. Unsupervised analysis, supervised analysis, univariate analysis, and pathway analysis were used to identify potential metabolic biomarkers of CRC. The level of twenty-five metabolites in CRC tissues were significantly altered compared to the matched adjacent non-tumor tissues. Four metabolites (lactic acid, alanine, phosphate, and aspartic acid) demonstrated good area under the curve (AUC) of Receiver- Operator Characteristic (ROC) with acceptable sensitivities and specificities, indicating their potential as important biomarkers for CRC. Alterations of amino acid metabolism and enhanced glycolysis may be major factors in the development and progression of colorectal cancer. Lactic acid, alanine, phosphate, and aspartic acid could be effective diagnostic indicators for CRC. PMID: 28475217 [PubMed - as supplied by publisher]

Metabolomic profiling and biochemical evaluation of the follicular fluid of endometriosis patients. Mol Biosyst. 2017 May 05;: Authors: Marianna S, Alessia P, Susan C, Francesca C, Angela S, Francesca C, Antonella N, Patrizia I, Nicola C, Emilio C Abstract Diseases are complex systems that can be studied through the integration of data derived from different disciplines to obtain a global and reliable picture of the biological phenomenon under investigation. Based on the recent observations that the metabolomics profiling of follicular fluids reflects the ovarian microenvironment of women and that endometriosis represents an example of complex diseases, clearly diagnosed by laparoscopy, we thought that the follicular fluids of endometriosis patients can represent a study model to evaluate the possibility of integrating data obtained by different approaches. Hence, the aim of this work was to analyze and integrate different clinical chemistry parameters with specific reference to the metabolic profile, inflammatory state and cell damage by a (1)H-NMR approach and biochemical analysis in the follicular fluids of women with different stages of endometriosis (I-II and III-IV) subjected to the In Vitro Fertilization (IVF) cycle. Our analysis evidenced that in the follicular fluids of endometriosis patients the levels of phospholipids, lactate, insulin, PTX3, CXCL8, CXCL10, CCL11 and VEGF were higher whereas those of some fatty acids, lysine, choline, glucose, aspartate, alanine, leucine, valine, proline, phosphocholine, total LDH as well its LDH-3 isoform were lower in comparison to the control group. The levels of LDHB, PTX3 and insulin receptor were also confirmed by RT-PCR applied on cumulus cells surrounding oocytes retrieved from the patients. The reduced oocyte quality observed in patients with endometriosis can be certainly correlated to the different levels of these molecules. These data represent how the integration of different experimental approaches may be useful for understanding the underlying mechanisms of a complex disease and can lead to a better clinical management of endometriosis. PMID: 28475193 [PubMed - as supplied by publisher]

LILY-lipidome isotope labeling of yeast: in vivo synthesis of (13)C labeled reference lipids for quantification by mass spectrometry. Analyst. 2017 May 05;: Authors: Rampler E, Coman C, Hermann G, Sickmann A, Ahrends R, Koellensperger G Abstract Quantification is an essential task in comprehensive lipidomics studies challenged by the high number of lipids, their chemical diversity and their dynamic range of the lipidome. In this work, we introduce lipidome isotope labeling of yeast (LILY) in order to produce (non-radioactive) isotopically labeled eukaryotic lipid standards in yeast for normalization and quantification in mass spectrometric assays. More specifically, LILY is a fast and efficient in vivo labeling strategy in Pichia pastoris for the production of (13)C labeled lipid library further paving the way to comprehensive compound-specific internal standardization in quantitative mass spectrometry based assays. More than 200 lipid species (from PA, PC, PE, PG, PI, PS, LysoGP, CL, DAG, TAG, DMPE, Cer, HexCer, IPC, MIPC) were obtained from yeast extracts with an excellent (13)C enrichment >99.5%, as determined by complementary high resolution mass spectrometry based shotgun and high resolution LC-MS/MS analysis. In a first proof of principle study we tested the relative and absolute quantification capabilities of the (13)C enriched lipids obtained by LILY using a parallel reaction monitoring based LC-MS approach. In relative quantification it could be shown that compound specific internal standardization was essential for the accuracy extending the linear dynamic range to four orders of magnitude. Excellent analytical figures of merit were observed for absolute quantification for a selected panel of 5 investigated glycerophospholipids (e.g. LOQs around 5 fmol absolute; typical concentrations ranging between 1 to 10 nmol per 10(8) yeast cell starting material; RSDs <10% (N = 4)). PMID: 28475182 [PubMed - as supplied by publisher]

The Use of "Omics" in Lactation Research in Dairy Cows. Int J Mol Sci. 2017 May 05;18(5): Authors: Li S, Wang Q, Lin X, Jin X, Liu L, Wang C, Chen Q, Liu J, Liu H Abstract "Omics" is the application of genomics, transcriptomics, proteomics, and metabolomics in biological research. Over the years, tremendous amounts of biological information has been gathered regarding the changes in gene, mRNA and protein expressions as well as metabolites in different physiological conditions and regulations, which has greatly advanced our understanding of the regulation of many physiological and pathophysiological processes. The aim of this review is to comprehensively describe the advances in our knowledge regarding lactation mainly in dairy cows that were obtained from the "omics" studies. The "omics" technologies have continuously been preferred as the technical tools in lactation research aiming to develop new nutritional, genetic, and management strategies to improve milk production and milk quality in dairy cows. PMID: 28475129 [PubMed - in process]

Related Articles Cowpea (Vigna unguiculata L. Walp.) Metabolomics: Osmoprotection as a Physiological Strategy for Drought Stress Resistance and Improved Yield. Front Plant Sci. 2017;8:586 Authors: Goufo P, Moutinho-Pereira JM, Jorge TF, Correia CM, Oliveira MR, Rosa EAS, António C, Trindade H Abstract Plants usually tolerate drought by producing organic solutes, which can either act as compatible osmolytes for maintaining turgor, or radical scavengers for protecting cellular functions. However, these two properties of organic solutes are often indistinguishable during stress progression. This study looked at individualizing properties of osmotic adjustment vs. osmoprotection in plants, using cowpea as the model species. Two cultivars were grown in well-watered soil, drought conditions, or drought followed by rewatering through fruit formation. Osmoadaptation was investigated in leaves and roots using photosynthetic traits, water homoeostasis, inorganic ions, and primary and secondary metabolites. Multifactorial analyses indicated allocation of high quantities of amino acids, sugars, and proanthocyanidins into roots, presumably linked to their role in growth and initial stress perception. Physiological and metabolic changes developed in parallel and drought/recovery responses showed a progressive acclimation of the cowpea plant to stress. Of the 88 metabolites studied, proline, galactinol, and a quercetin derivative responded the most to drought as highlighted by multivariate analyses, and their correlations with yield indicated beneficial effects. These metabolites accumulated differently in roots, but similarly in leaves, suggesting a more conservative strategy to cope with drought in the aerial parts. Changes in these compounds roughly reflected energy investment in protective mechanisms, although the ability of plants to adjust osmotically through inorganic ions uptake could not be discounted. PMID: 28473840 [PubMed - in process]

Related Articles Metabolic Profiles in Cell Lines Infected with Classical Swine Fever Virus. Front Microbiol. 2017;8:691 Authors: Gou H, Zhao M, Yuan J, Xu H, Ding H, Chen J Abstract Viruses require energy and biosynthetic precursors from host cells for replication. An understanding of the metabolic interplay between classical swine fever virus (CSFV) and host cells is important for exploring the complex pathological mechanisms of classical swine fever (CSF). In the current study, and for the first time, we utilized an approach involving gas chromatography coupled with mass spectrometry (GC-MS) to examine the metabolic profiles within PK-15 and 3D4/2 cells infected with CSFV. The differential metabolites of PK-15 cells caused by CSFV infection mainly included the decreased levels of glucose 6-phosphate [fold change (FC) = -1.94)] and glyceraldehyde-3-phosphate (FC = -1.83) during glycolysis, ribulose 5-phosphate (FC = -1.51) in the pentose phosphate pathway, guanosine (FC = -1.24) and inosine (FC = -1.16) during purine biosynthesis, but the increased levels of 2-ketoisovaleric acid (FC = 0.63) during the citrate cycle, and ornithine (FC = 0.56) and proline (FC = 0.62) during arginine and proline metabolism. However, metabolite changes caused by CSFV infection in 3D4/2 cells included the reduced glyceraldehyde-3-phosphate (FC = -0.77) and pyruvic acid (FC = -1.42) during glycolysis, 2-ketoglutaric acid (FC = -1.52) in the citrate cycle, and the elevated cytosine (FC = 2.15) during pyrimidine metabolism. Our data showed that CSFV might rebuild cellular metabolic programs, thus aiding viral replication. These findings may be important in developing targets for new biomarkers for the diagnosis and identification of enzyme inhibitors or metabolites as antiviral drugs, or screening viral gene products as vaccines. PMID: 28473819 [PubMed - in process]