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

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 2 hours 45 min ago

metabolomics; +35 new citations

Thu, 16/05/2019 - 12:46
35 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/05/16PubMed 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.

Mass spectral databases for metabolomics: How to build a consistently annotated mass spectral database from pure reference compounds analyzed under electrospray ionization conditions?

Wed, 15/05/2019 - 12:39
Related Articles Mass spectral databases for metabolomics: How to build a consistently annotated mass spectral database from pure reference compounds analyzed under electrospray ionization conditions? J Mass Spectrom. 2019 May 13;: Authors: Damont A, Olivier MF, Warnet A, Lyan B, Pujos-Guillot E, Jamin EL, Debrauwer L, Bernillon S, Junot C, Tabet JC, Fenaille F Abstract Nowadays, high-resolution mass spectrometry is widely used for metabolomic studies. Thanks to its high sensitivity, it enables the detection of a large range of metabolites. In metabolomics, the continuous quest for a metabolite identification as complete and accurate as possible has led during the last decade to an ever increasing development of public MS databases (including LC-MS data) concomitantly with bioinformatic tool expansion. To facilitate the annotation process of MS profiles obtained from biological samples, but also to ease data sharing, exchange and exploitation, the standardization and harmonization of the way to describe and annotate mass spectra seemed crucial to us. Indeed, under electrospray (ESI) conditions, a single metabolite does not produce a unique ion corresponding to its protonated or deprotonated form but could lead to a complex mixture of signals. These MS signals result from the existence of different natural isotopologues of the same compound and also to the potential formation of adduct ions, homo and hetero-multimeric ions, fragment ions resulting from "prompt" in-source dissociations. As a joint reflection process within the French Infrastructure for Metabolomics and Fluxomics (MetaboHUB) and with the purpose of developing a robust and exchangeable annotated MS database made from pure reference compounds (chemical standards) analysis, it appeared to us that giving the metabolomics community some clues to standardize and unambiguously annotate each MS feature, was a prerequisite to data entry and further efficient querying of the database. The use of a harmonized notation is also mandatory for inter-laboratory MS data exchange. Additionally, thorough description of the variety of MS signals arising from the analysis of a unique metabolite might provide greater confidence on its annotation. PMID: 31083780 [PubMed - as supplied by publisher]

The Health Promoting Bioactivities of Lactuca sativa can be Enhanced by Genetic Modulation of Plant Secondary Metabolites.

Wed, 15/05/2019 - 12:39
Related Articles The Health Promoting Bioactivities of Lactuca sativa can be Enhanced by Genetic Modulation of Plant Secondary Metabolites. Metabolites. 2019 May 12;9(5): Authors: Ismail H, Gillespie AL, Calderwood D, Iqbal H, Gallagher C, Chevallier OP, Elliott CT, Pan X, Mirza B, Green BD Abstract Plant secondary metabolites are protective dietary constituents and rol genes evidently increase the synthesis of these versatile phytochemicals. This study subjected a globally important vegetable, lettuce (Lactuca sativa) to a combination of untargeted metabolomics (LC-QTof-MS) and in vitro bioactivity assays. Specifically, we examined the differences between untransformed cultured lettuce (UnT), lettuce transformed with either rolABC (RA) or rolC (RC) and commercially grown (COM) lettuce. Of the 5333 metabolite features aligned, deconvoluted and quantified 3637, 1792 and 3737 significantly differed in RA, RC and COM, respectively, compared with UnT. In all cases the number of downregulated metabolites exceeded the number increased. In vitro bioactivity assays showed that RA and RC (but not COM) significantly improved the ability of L. sativa to inhibit α-glucosidase, inhibit dipeptidyl peptidase-4 (DPP-4) and stimulate GLP-1 secretion. We putatively identified 76 lettuce metabolites (sesquiterpene lactones, non-phenolic and phenolic compounds) some of which were altered by several thousand percent in RA and RC. Ferulic acid levels increased 3033-9777%, aminooxononanoic acid increased 1141-1803% and 2,3,5,4'tetrahydroxystilbene-2-O-β-d-glucoside increased 40,272-48,008%. Compound activities were confirmed using commercially obtained standards. In conclusion, rol gene transformation significantly alters the metabolome of L.sativa and enhances its antidiabetic properties. There is considerable potential to exploit rol genes to modulate secondary metabolite production for the development of novel functional foods. This investigation serves as a new paradigm whereby genetic manipulation, metabolomic analysis and bioactivity techniques can be combined to enable the discovery of novel natural bioactives and determine the functional significance of plant metabolites. PMID: 31083625 [PubMed]

Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging.

Wed, 15/05/2019 - 12:39
Related Articles Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging. Biology (Basel). 2019 May 11;8(2): Authors: Wimalawansa SJ Abstract Recent advances in vitamin D research indicate that this vitamin, a secosteroid hormone, has beneficial effects on several body systems other than the musculoskeletal system. Both 25 dihydroxy vitamin D [25(OH)2D] and its active hormonal form, 1,25-dihydroxyvitamin D [1,25(OH)2D] are essential for human physiological functions, including damping down inflammation and the excessive intracellular oxidative stresses. Vitamin D is one of the key controllers of systemic inflammation, oxidative stress and mitochondrial respiratory function, and thus, the aging process in humans. In turn, molecular and cellular actions form 1,25(OH)2D slow down oxidative stress, cell and tissue damage, and the aging process. On the other hand, hypovitaminosis D impairs mitochondrial functions, and enhances oxidative stress and systemic inflammation. The interaction of 1,25(OH)2D with its intracellular receptors modulates vitamin D-dependent gene transcription and activation of vitamin D-responsive elements, which triggers multiple second messenger systems. Thus, it is not surprising that hypovitaminosis D increases the incidence and severity of several age-related common diseases, such as metabolic disorders that are linked to oxidative stress. These include obesity, insulin resistance, type 2 diabetes, hypertension, pregnancy complications, memory disorders, osteoporosis, autoimmune diseases, certain cancers, and systemic inflammatory diseases. Vitamin D adequacy leads to less oxidative stress and improves mitochondrial and endocrine functions, reducing the risks of disorders, such as autoimmunity, infections, metabolic derangements, and impairment of DNA repair; all of this aids a healthy, graceful aging process. Vitamin D is also a potent anti-oxidant that facilitates balanced mitochondrial activities, preventing oxidative stress-related protein oxidation, lipid peroxidation, and DNA damage. New understandings of vitamin D-related advances in metabolomics, transcriptomics, epigenetics, in relation to its ability to control oxidative stress in conjunction with micronutrients, vitamins, and antioxidants, following normalization of serum 25(OH)D and tissue 1,25(OH)2D concentrations, likely to promise cost-effective better clinical outcomes in humans. PMID: 31083546 [PubMed]

Metabolomics Studies to Assess Biological Functions of Vitamin E Nicotinate.

Wed, 15/05/2019 - 12:39
Related Articles Metabolomics Studies to Assess Biological Functions of Vitamin E Nicotinate. Antioxidants (Basel). 2019 May 11;8(5): Authors: Marcocci L, Suzuki YJ Abstract Vitamin E nicotinate (tocopherol nicotinate, tocopheryl nicotinate; TN) is an ester of two vitamins, tocopherol (vitamin E) and niacin (vitamin B3), in which niacin is linked to the hydroxyl group of active vitamin E. This vitamin E ester can be chemically synthesized and is used for supplementation. However, whether TN is formed in the biological system was unclear. Our laboratory previously detected TN in rat heart tissues, and its level was 30-fold lower in a failing heart (Wang et al., PLoS ONE 2017, 12, e0176887). The rat diet used in these experiments contained vitamin E acetate (tocopherol acetate; TA) and niacin separately, but not in the form of TN. Since only TN, but not other forms of vitamin E, was decreased in heart failure, the TN structure may elicit biologic functions independent of serving as a source of active vitamin E antioxidant. To test this hypothesis, the present study performed metabolomics to compare effects of TN on cultured cells to those of TA plus niacin added separately (TA + N). Human vascular smooth muscle cells were treated with TN or with TA + N (100 μM) for 10 min. Metabolite profiles showed that TN and TA + N influenced the cells differentially. TN effectively upregulated various primary fatty acid amides including arachidonoylethanoamine (anandamide/virodhamine) and palmitamide. TN also activated mitogen-activated protein kinases. These results suggest a new biological function of TN to elicit cell signaling. PMID: 31083512 [PubMed]

GC⁻MS-Based Nontargeted and Targeted Metabolic Profiling Identifies Changes in the Lentinula edodes Mycelial Metabolome under High-Temperature Stress.

Wed, 15/05/2019 - 12:39
Related Articles GC⁻MS-Based Nontargeted and Targeted Metabolic Profiling Identifies Changes in the Lentinula edodes Mycelial Metabolome under High-Temperature Stress. Int J Mol Sci. 2019 May 10;20(9): Authors: Zhao X, Chen M, Zhao Y, Zha L, Yang H, Wu Y Abstract To clarify the physiological mechanism of the Lentinula edodes (L. edodes) response to high-temperature stress, two strains of L. edodes with different tolerances were tested at different durations of high temperature, and the results showed that there were significant changes in their phenotypes and physiology. To further explore the response mechanism, we established a targeted GC-MS-based metabolomics workflow comprising a standardized experimental setup for growth, treatment and sampling of L. edodes mycelia, and subsequent GC-MS analysis followed by data processing and evaluation of quality control (QC) measures using tailored statistical and bioinformatic tools. This study identified changes in the L. edodes mycelial metabolome following different time treatments at high temperature based on nontargeted metabolites with GC-MS and further adopted targeted metabolomics to verify the results of the analysis. After multiple statistical analyses were carried out using SIMCA software, 74 and 108 differential metabolites were obtained, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the metabolic pathways with significant changes included those related to the following: amino acid metabolism, the glycolysis pathway, the tricarboxylic acid (TCA) cycle, and sugar metabolism. Most amino acids and carbohydrates enriched in these metabolic pathways were upregulated in strain 18, downregulated in strain 18N44, or the synthesis in strain 18 was higher than that in strain 18N44. This result was consistent with the physiological phenotypic characteristics of the two strains under high-temperature stress and revealed the reason why strain 18N44 was more heat-sensitive. At the same time, under high temperature, the decrease of intermediate products in glycolysis and the TCA cycle resulted in carbon starvation and insufficient energy metabolism, thus inhibiting the growth of L. edodes. In addition, the results also showed that the metabolites produced by different L. edodes strains under high-temperature stress were basically the same. However, different strains had species specificity, so the changes in the content of metabolites involved in the response to high-temperature stress were different. This provides a theoretical basis for further understanding the mechanism of the L. edodes response to high temperature and can be used to establish an evaluation system of high-temperature-resistant strains and lay the foundation for molecular breeding of new L. edodes strains resistant to high temperature. PMID: 31083449 [PubMed - in process]

White Adipose Tissue Response of Obese Mice to Ambient Oxygen Restriction at Thermoneutrality: Response Markers Identified, but no WAT Inflammation.

Wed, 15/05/2019 - 12:39
Related Articles White Adipose Tissue Response of Obese Mice to Ambient Oxygen Restriction at Thermoneutrality: Response Markers Identified, but no WAT Inflammation. Genes (Basel). 2019 May 10;10(5): Authors: Hoevenaars FPM, Keijer J, van der Stelt I, Duivenvoorde LPM, Herreman L, van Nes R, Friedecký D, Hegeman MA, van Schothorst EM Abstract Obesity is associated with white adipose tissue (WAT) hypoxia and inflammation. We aimed to test whether mild environmental oxygen restriction (OxR, 13% O2), imposing tissue hypoxia, triggers WAT inflammation in obese mice. Thirteen weeks diet-induced obese male adult C57BL/6JOlaHsd mice housed at thermoneutrality were exposed for five days to OxR versus normoxia. WAT and blood were isolated and used for analysis of metabolites and adipokines, WAT histology and macrophage staining, and WAT transcriptomics. OxR increased circulating levels of haemoglobin and haematocrit as well as hypoxia responsive transcripts in WAT and decreased blood glucose, indicating systemic and tissue hypoxia. WAT aconitase activity was inhibited. Macrophage infiltration as marker for WAT inflammation tended to be decreased, which was supported by down regulation of inflammatory genes S100a8, Ccl8, Clec9a, Saa3, Mgst2, and Saa1. Other down regulated processes include cytoskeleton remodelling and metabolism, while response to hypoxia appeared most prominently up regulated. The adipokines coiled-coil domain containing 3 (CCDC3) and adiponectin, as well as the putative WAT hormone cholecystokinin (CCK), were reduced by OxR on transcript (Cck, Ccdc3) and/or serum protein level (adiponectin, CCDC3). Conclusively, our data demonstrate that also in obese mice OxR does not trigger WAT inflammation. However, OxR does evoke a metabolic response in WAT, with CCDC3 and adiponectin as potential markers for systemic or WAT hypoxia. PMID: 31083422 [PubMed]

Improved Algal Toxicity Test System for Robust Omics-Driven Mode-of-Action Discovery in Chlamydomonas reinhardtii.

Wed, 15/05/2019 - 12:39
Related Articles Improved Algal Toxicity Test System for Robust Omics-Driven Mode-of-Action Discovery in Chlamydomonas reinhardtii. Metabolites. 2019 May 10;9(5): Authors: Schade S, Butler E, Gutsell S, Hodges G, Colbourne JK, Viant MR Abstract Algae are key components of aquatic food chains. Consequently, they are internationally recognised test species for the environmental safety assessment of chemicals. However, existing algal toxicity test guidelines are not yet optimized to discover molecular modes of action, which require highly-replicated and carefully controlled experiments. Here, we set out to develop a robust, miniaturised and scalable Chlamydomonas reinhardtii toxicity testing approach tailored to meet these demands. We primarily investigated the benefits of synchronised cultures for molecular studies, and of exposure designs that restrict chemical volatilisation yet yield sufficient algal biomass for omics analyses. Flow cytometry and direct-infusion mass spectrometry metabolomics revealed significant and time-resolved changes in sample composition of synchronised cultures. Synchronised cultures in sealed glass vials achieved adequate growth rates at previously unachievably-high inoculation cell densities, with minimal pH drift and negligible chemical loss over 24-h exposures. Algal exposures to a volatile test compound (chlorobenzene) yielded relatively high reproducibility of metabolic phenotypes over experimental repeats. This experimental test system extends existing toxicity testing formats to allow highly-replicated, omics-driven, mode-of-action discovery. PMID: 31083411 [PubMed]

T-Probe: An Integrated Microscale Device for Online In Situ Single Cell Analysis and Metabolic Profiling Using Mass Spectrometry.

Wed, 15/05/2019 - 12:39
Related Articles T-Probe: An Integrated Microscale Device for Online In Situ Single Cell Analysis and Metabolic Profiling Using Mass Spectrometry. Anal Chem. 2018 09 18;90(18):11078-11085 Authors: Liu R, Pan N, Zhu Y, Yang Z Abstract The exploration of single cells reveals cell heterogeneity and biological principle of cellular metabolism. Although a number of mass spectrometry (MS) based single cell MS (SCMS) techniques have been dedicatedly developed with high efficiency and sensitivity, limitations still exist. In this work, we introduced a microscale multifunctional device, the T-probe, which integrates cellular contents extraction and immediate ionization, to implement online in situ SCMS analysis at ambient conditions with minimal sample preparation. With high sensitivity and reproducibility, the T-probe was employed for MS analysis of single HeLa cells under control and anticancer drug treatment conditions. Intracellular species and xenobiotic metabolites were detected, and changes of cellular metabolic profiles induced by drug treatment were measured. Combining SCMS experiments with statistical data analyses, including Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) and two-sample t-test, we provided biological insights into cellular metabolic response to drug treatment. Online MS/MS analysis was conducted at single cell level to identify species of interest, including endogenous metabolites and the drug compound. Using the T-probe SCMS technique combined with comprehensive data analyses, we provide an approach to understanding cellular metabolism and evaluate chemotherapies at the single cell level. PMID: 30119596 [PubMed - indexed for MEDLINE]

metabolomics; +17 new citations

Tue, 14/05/2019 - 15:26
17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/05/14PubMed 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.

metabolomics; +17 new citations

Tue, 14/05/2019 - 12:22
17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/05/14PubMed 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.

Changes in the metabolic composition of storage solution with prolonged cold ischemia of the uterus.

Mon, 13/05/2019 - 15:01
Related Articles Changes in the metabolic composition of storage solution with prolonged cold ischemia of the uterus. J Assist Reprod Genet. 2019 May 12;: Authors: Tardieu A, Chazelas P, Faye PA, Favreau F, Nadal-Desbarats L, Sallée C, Margueritte F, Couquet CY, Marquet P, Guellec CB, Gauthier T Abstract INTRODUCTION: The development of uterine transplantation (UTx) from deceased donors requires knowledge of the tolerance of the uterus to prolonged cold ischemia (CI). This can be evaluated through the use of biological parameters to assess degradation of the organ between its procurement and transplantation. The objective of this study was to analyze changes in the metabolic composition of the storage solution in cases of prolonged CI in uteri from ewes. METHODS: Eighteen uterine auto-transplantations were performed in ewes. CI time was 1 h (T1) or 24 h (T24). Samples of Celsior® were taken when the explanted uterus was flushed (T0) and at the end of CI. A dual approach to metabolic analyses was followed: targeted biochemical analyses targeting several predefined metabolites and non-targeted metabolomics analyses based on nuclear magnetic resonance (NMR). RESULTS: Metabolic analyses were performed on 16 explanted uteri. Metabolomic profiles differed significantly between T1 and T24 (p = 0.003). Hypoxia-associated degradation of the organ was demonstrated by the significantly higher lactate levels at T24 than at T1 (p < 0.05), accompanied by cell lysis, and significantly higher levels of creatine kinase activity in T24 than in T1 uteri (p < 0.05). Oxidative stress increased over time, with a significantly higher oxidized glutathione/glutathione ratio for T24 than for T1 uteri (p < 0.05). CONCLUSION: The metabolic results indicate a significant degradation of the uterus during 24 h of CI. Metabolic analysis of the storage solution could be used as a non-invasive tool for evaluating uterine degradation during CI before transplantation. PMID: 31079269 [PubMed - as supplied by publisher]

Dydrogesterone exposure induces zebrafish ovulation but leads to oocytes over-ripening: An integrated histological and metabolomics study.

Mon, 13/05/2019 - 15:01
Related Articles Dydrogesterone exposure induces zebrafish ovulation but leads to oocytes over-ripening: An integrated histological and metabolomics study. Environ Int. 2019 May 09;128:390-398 Authors: Jiang YX, Shi WJ, Ma DD, Zhang JN, Ying GG, Zhang H, Ong CN Abstract Dydrogesterone (DDG) is a synthetic progestin widely used in numerous gynecological diseases. DDG has been shown to disturb fish reproduction, however, the mechanism is still unclear. Here we studied the histological changes and differences of metabolome between exposed and control fish gonads after exposure of zebrafish (Danio rerio) embryos to 2.8, 27.6, and 289.8 ng/L DDG until sexual maturity for a total of 140 days. Dydrogesterone exposure led to male-biased zebrafish sex ratios. Histological examination revealed that DDG induced postovulatory follicles and atretic follicles in the ovary of the female fish. Postovulatory follicles indicated the occurrence of ovulation. DDG also increased spermatids and spermatozoa in the male fish testis, suggesting promotion of spermatogenesis. Ovarian metabolome showed that DDG increased the concentrations of free amino acids, urea, putrescine, free fatty acids, acylcarnitines, lysophospholipids, and other metabolites catabolized from phospholipids. Most of these metabolites are biodegradation products of proteins and lipids, suggesting the existence of ovulated oocytes over-ripening. Further, DDG upregulated arachidonic acid (AA) and its 5‑lipoxygenase (5-LOX) metabolites 5‑oxo‑6,8,11,14‑eicosatetraenoic acid (5-oxo-ETE) in the ovary, which could lead to suppression of AA cyclooxygenase (COX) metabolite prostaglandin F2α (PGF2α). It is believed that AA induced oocyte maturation, while 5-oxo-ETE and related metabolites in purinergic signaling promoted ovulation. Whereas, the suppression of PGF2α production might block spawning and damaged follicular tissue digestion, which explained the oocytes over-ripening and atretic follicles in the treated ovary. Overall, our results suggested that DDG exposure induced zebrafish oocyte maturation and ovulation but led to oocytes over-ripening via the AA metabolic pathway and purinergic signaling. PMID: 31078873 [PubMed - as supplied by publisher]

2H and 13C metabolic flux analysis elucidates in vivo thermodynamics of the ED pathway in Zymomonas mobilis.

Mon, 13/05/2019 - 15:01
Related Articles 2H and 13C metabolic flux analysis elucidates in vivo thermodynamics of the ED pathway in Zymomonas mobilis. Metab Eng. 2019 May 09;: Authors: Jacobson TB, Adamczyk PA, Stevenson DM, Regner M, Ralph J, Reed J, Amador-Noguez D Abstract Zymomonas mobilis is an industrially relevant bacterium notable for its ability to rapidly ferment simple sugars to ethanol using the Entner-Doudoroff (ED) glycolytic pathway, an alternative to the well-known Embden-Meyerhof-Parnas (EMP) pathway used by most organisms. Recent computational studies have predicted that the ED pathway is substantially more thermodynamically favorable than the EMP pathway, a potential factor explaining the high glycolytic rate in Z. mobilis. Here, to investigate the in vivo thermodynamics of the ED pathway and central carbon metabolism in Z. mobilis, we implemented a network-level approach that integrates quantitative metabolomics with 2H and 13C metabolic flux analysis to estimate reversibility and Gibbs free energy (ΔG) of metabolic reactions. This analysis revealed a strongly thermodynamically favorable ED pathway in Z. mobilis that is nearly twice as favorable as the EMP pathway in E. coli or S. cerevisiae. The in vivo step-by-step thermodynamic profile of the ED pathway was highly similar to previous in silico predictions, indicating that maximizing ΔG for each pathway step likely constitutes a cellular objective in Z. mobilis. Our analysis also revealed novel features of Z. mobilis metabolism, including phosphofructokinase-like enzyme activity, tricarboxylic acid cycle anaplerosis via PEP carboxylase, and a metabolic imbalance in the pentose phosphate pathway resulting in excretion of shikimate pathway intermediates. The integrated approach we present here for in vivo ΔG quantitation may be applied to the thermodynamic profiling of pathways and metabolic networks in other microorganisms and will contribute to the development of quantitative models of metabolism. PMID: 31078792 [PubMed - as supplied by publisher]

Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort.

Mon, 13/05/2019 - 15:01
Related Articles Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort. Alzheimers Dement. 2019 Apr 28;: Authors: Kim M, Snowden S, Suvitaival T, Ali A, Merkler DJ, Ahmad T, Westwood S, Baird A, Proitsi P, Nevado-Holgado A, Hye A, Bos I, Vos S, Vandenberghe R, Teunissen C, Ten Kate M, Scheltens P, Gabel S, Meersmans K, Blin O, Richardson J, De Roeck E, Sleegers K, Bordet R, Rami L, Kettunen P, Tsolaki M, Verhey F, Sala I, Lléo A, Peyratout G, Tainta M, Johannsen P, Freund-Levi Y, Frölich L, Dobricic V, Engelborghs S, Frisoni GB, Molinuevo JL, Wallin A, Popp J, Martinez-Lage P, Bertram L, Barkhof F, Ashton N, Blennow K, Zetterberg H, Streffer J, Visser PJ, Lovestone S, Legido-Quigley C Abstract INTRODUCTION: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers. METHODS: This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis. RESULTS: Eight metabolites were associated with amyloid β and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory. DISCUSSION: PFAMs have been found increased and associated with amyloid β burden in CSF and clinical measures. PMID: 31078433 [PubMed - as supplied by publisher]

Evaluating sub-lethal stress from Roundup® exposure in Artemia franciscana using 1H NMR and GC-MS.

Sun, 12/05/2019 - 14:34
Related Articles Evaluating sub-lethal stress from Roundup® exposure in Artemia franciscana using 1H NMR and GC-MS. Aquat Toxicol. 2019 May 01;212:77-87 Authors: Morgan MA, Griffith CM, Dinges MM, Lyon YA, Julian RR, Larive CK Abstract Global salinization trends present an urgent need for methods to monitor aquatic ecosystem health and characterize known and emerging stressors for water bodies that are becoming increasingly saline. Environmental metabolomics methods that combine quantitative measurements of metabolite levels and multivariate statistical analysis are powerful tools for ascertaining biological impacts and identifying potential biomarkers of exposure. We propose the use of the saltwater aquatic crustacean, Artemia franciscana, as a model organism for environmental metabolomics in saltwater ecosystems. Artemia are a good choice for ecotoxicity assays and metabolomics analysis because they have a short life cycle, their hemolymph is rich in metabolites and they tolerate a wide salinity range. In this work we explore the potential of Artemia franciscana for environmental metabolomics through exposure to the broad-spectrum herbicide, glyphosate. The LC50 for a 48 h exposure of Roundup® was determined to be 237 ± 23 ppm glyphosate in the Roundup® formulation. Artemia cysts were hatched and exposed to sub-lethal glyphosate concentrations of 1.00, 10.0, 50.0, or 100 ppm glyphosate in Roundup®. We profiled 48 h old Artemia extracts using 1H NMR and GC-MS. Dose-dependent metabolic perturbation was evident for several metabolites using univariate and multivariate analyses. Metabolites significantly affected by Roundup® exposure included aspartate, formate, betaine, glucose, tyrosine, phenylalanine, gadusol, and isopropylamine. Biochemical pathway analysis with the KEGG database suggests impairment of carbohydrate and energy metabolism, folate-mediated one-carbon metabolism, Artemia molting and development, and microbial metabolism. PMID: 31077969 [PubMed - as supplied by publisher]

Experiments with direct detection of multiple FIDs.

Sun, 12/05/2019 - 14:34
Related Articles Experiments with direct detection of multiple FIDs. J Magn Reson. 2019 Apr 30;304:16-34 Authors: Kupče Ē, Mote KR, Madhu PK Abstract Pulse schemes with direct observation of multiple free induction decays (FIDs) offer a dramatic increase in the spectral information content of NMR experiments and often yield substantial improvement in measurement sensitivity per unit time. Availability of multiple receivers on the state-of-the-art commercial spectrometers allows spectra from different nuclear species to be recorded in parallel routinely. Experiments with multi-FID detection have been designed with both, homonuclear and multinuclear acquisition. We provide a brief overview of such techniques designed for applications in liquid- and solid- state NMR as well as in hyperpolarized samples. Here we show how these techniques have led to design of experiments that allow structure elucidation of small molecules and resonance assignment in proteins from a single measurement. Probes with multiple RF micro-coils routed to multiple NMR receivers provide an alternative way of increasing the throughput of modern NMR systems. Solid-state NMR experiments have also benefited immensely from both parallel and simultaneous FID acquisition in a variety of multi-dimensional pulse schemes. We believe that multi-FID detection will become an essential component of the future NMR methodologies effectively increasing the information content of NMR experiments and reducing the cost of NMR analysis. PMID: 31077929 [PubMed - as supplied by publisher]

Saliva NMR metabolomics: analytical issues in paediatric oral health research.

Sun, 12/05/2019 - 14:34
Related Articles Saliva NMR metabolomics: analytical issues in paediatric oral health research. Oral Dis. 2019 May 11;: Authors: Pereira JL, Duarte D, Carneiro TJ, Ferreira S, Cunha B, Soares D, Costa AL, Gil AM Abstract OBJECTIVES: Saliva metabolome is a promising diagnostic tool concerning oral and systemic diseases. We aimed at establishing a suitable protocol for saliva collection and gauging the relative impacts of gender, dentition stage and caries on the saliva metabolome of a small children cohort. SUBJECTS AND METHODS: A Nuclear Magnetic Resonance-based metabolomics cross-sectional study of children saliva (n=38) compared the effects of i) stimulation and unstimulation conditions and ii) collection through passive drool and using an absorbing device. Multivariate and univariate statistical analysis were applied to evaluate such effects, and those related to gender, dentition stage and caries. RESULTS: No significant differences were found between unstimulated and stimulated saliva and the former was used for subsequent studies. Swab collection induced significant changes in sample composition, indicating passive drool as preferential. The impacts of gender and dentition stage were not significant compared to that of caries, which induced variations in the levels of 21 metabolites. These comprised amino acids and monosaccharides observed for the first time to our knowledge regarding children caries, suggesting protein hydrolysis and deglycosylation. CONCLUSIONS: Unstimulated passive drool saliva metabolome may carry a caries signature. This article is protected by copyright. All rights reserved. PMID: 31077633 [PubMed - as supplied by publisher]

Effects of Thiosulfate as a Sulfur Source on Plant Growth, Metabolites Accumulation and Gene Expression in Arabidopsis and Rice.

Sun, 12/05/2019 - 14:34
Related Articles Effects of Thiosulfate as a Sulfur Source on Plant Growth, Metabolites Accumulation and Gene Expression in Arabidopsis and Rice. Plant Cell Physiol. 2019 May 11;: Authors: Nakajima T, Kawano Y, Ohtsu I, Maruyuama-Nakashita A, Allahham A, Sato M, Sawada Y, Hirai MY, Yokoyama T, Ohkama-Ohtsu N Abstract Plants are considered to absorb sulfur from their roots in the form of sulfate. In bacteria like Escherichia coli, thiosulfate is a preferred sulfur source. It is converted into cysteine (Cys). This transformation consumes less NADPH and ATP than sulfate assimilation into Cys. In Saccharomyces cerevisiae, thiosulfate promoted growth more than sulfate. In the present study, the availability of thiosulfate, the metabolite transformations, and gene expressions it induces were investigated in Arabidopsis and rice as model dicots and monocots, respectively. In Arabidopsis the thiosulfate-amended plants had lower biomass than those receiving sulfate when sulfur concentrations in the hydroponic medium were above 300 μM. In contrast, rice biomass was similar for plants raised on thiosulfate and sulfate at 300 μM sulfur. Therefore, both plants can use thiosulfate but it is a better sulfur source for rice. In both plants, thiosulfate levels significantly increased in roots following thiosulfate application, indicating that the plants absorbed thiosulfate into their root cells. Thiosulfate is metabolized in plants by a different pathway from that used for sulfate metabolism. Thiosulfate increases plant sulfide and cysteine-persulfide levels which means that plants are in a more reduced state with thiosulfate than with sulfate. The microarray analysis of Arabidopsis roots revealed that 13 genes encoding Cys-rich proteins were upregulated more with thiosulfate than with sulfate. These results together with those of the widely-targeted metabolomics analysis were used to proposes a thiosulfate assimilation pathway in plants. PMID: 31077319 [PubMed - as supplied by publisher]

Lipidomics in Ulcerative Colitis Reveal Alteration in Mucosal Lipid Composition Associated With the Disease State.

Sun, 12/05/2019 - 14:34
Related Articles Lipidomics in Ulcerative Colitis Reveal Alteration in Mucosal Lipid Composition Associated With the Disease State. Inflamm Bowel Dis. 2019 May 11;: Authors: Diab J, Hansen T, Goll R, Stenlund H, Ahnlund M, Jensen E, Moritz T, Florholmen J, Forsdahl G Abstract BACKGROUND: The onset of ulcerative colitis (UC) is associated with alterations in lipid metabolism and a disruption of the balance between pro- and anti-inflammatory molecules. Only a few studies describe the mucosal lipid biosignatures during active UC. Moreover, the dynamics of lipid metabolism in the remission state is poorly defined. Therefore, this study aims to characterize mucosal lipid profiles in treatment-naïve UC patients and deep remission UC patients compared with healthy subjects. METHODS: Treatment-naïve UC patients (n = 21), UC patients in deep remission (n = 12), and healthy volunteers (n = 14) were recruited. The state of deep remission was defined by histological and immunological remission defined by a normalized TNF-α gene expression. Mucosa biopsies were collected by colonoscopy. Lipid analysis was performed by means of ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS-MS). In total, 220 lipids from 11 lipid classes were identified. RESULTS: The relative concentration of 122 and 36 lipids was altered in UC treatment-naïve patients and UC remission patients, respectively, compared with healthy controls. The highest number of significant variations was in the phosphatidylcholine (PC), ceramide (Cer), and sphingomyelin (SM) composition. Multivariate analysis revealed discrimination among the study groups based on the lipid profile. Furthermore, changes in phosphatidylethanolamine(38:3), Cer(d18:1/24:0), and Cer(d18:1/24:2) were most distinctive between the groups. CONCLUSION: This study revealed a discriminant mucosal lipid composition pattern between treatment-naïve UC patients, deep remission UC patients, and healthy controls. We report several distinctive lipids, which might be involved in the inflammatory response in UC, and could reflect the disease state. PMID: 31077307 [PubMed - as supplied by publisher]

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