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

Integration of flux measurements to resolve changes in anabolic and catabolic metabolism in cardiac myocytes.

Sat, 15/07/2017 - 13:41
Integration of flux measurements to resolve changes in anabolic and catabolic metabolism in cardiac myocytes. Biochem J. 2017 Jul 13;: Authors: Gibb AA, Lorkiewicz PK, Zheng YT, Zhang X, Bhatnagar A, Jones SP, Hill BG Abstract Although ancillary pathways of glucose metabolism are critical for synthesizing cellular building blocks and modulating stress responses, how they are regulated remains unclear.  In this study, we used radiometric glycolysis assays, [(13)C6]-glucose isotope tracing, and extracellular flux analysis to understand how phosphofructokinase (PFK)-mediated changes in glycolysis regulate glucose carbon partitioning into catabolic and anabolic pathways. Expression of kinase-deficient or phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in rat neonatal cardiomyocytes coordinately regulated glycolytic rate and lactate production. Nevertheless, in all groups, >40% of glucose consumed by the cells was unaccounted for via catabolism to pyruvate, which suggests entry of glucose carbons into ancillary pathways branching from metabolites formed in the preparatory phase of glycolysis. Analysis of (13)C fractional enrichment patterns suggests that PFK activity regulates glucose carbon incorporation directly into the ribose and the glycerol moieties of purines and phospholipids, respectively. Pyrimidines, UDP-N-acetyl-hexosamine, and the fatty acyl chains of phosphatidylinositol and triglycerides showed lower (13)C incorporation under conditions of high PFK activity; the isotopologue (13)C enrichment pattern of each metabolite indicated limitations in mitochondria-engendered oxaloacetate, acetyl CoA, and fatty acids. Consistent with this notion, high glycolytic rate diminished mitochondrial activity and the coupling of glycolysis to glucose oxidation. These findings suggest that a major portion of intracellular glucose in cardiac myocytes is apportioned for ancillary biosynthetic reactions and that PFK coordinates the activities of the pentose phosphate, hexosamine biosynthetic, and glycerolipid synthesis pathways by directly modulating glycolytic intermediate entry into auxiliary glucose metabolism pathways and indirectly regulating mitochondrial cataplerosis. PMID: 28706006 [PubMed - as supplied by publisher]

Molecular definitions of autophagy and related processes.

Sat, 15/07/2017 - 13:41
Related Articles Molecular definitions of autophagy and related processes. EMBO J. 2017 Jul 03;36(13):1811-1836 Authors: Galluzzi L, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM, Cecconi F, Choi AM, Chu CT, Codogno P, Colombo MI, Cuervo AM, Debnath J, Deretic V, Dikic I, Eskelinen EL, Fimia GM, Fulda S, Gewirtz DA, Green DR, Hansen M, Harper JW, Jäättelä M, Johansen T, Juhasz G, Kimmelman AC, Kraft C, Ktistakis NT, Kumar S, Levine B, Lopez-Otin C, Madeo F, Martens S, Martinez J, Melendez A, Mizushima N, Münz C, Murphy LO, Penninger JM, Piacentini M, Reggiori F, Rubinsztein DC, Ryan KM, Santambrogio L, Scorrano L, Simon AK, Simon HU, Simonsen A, Tavernarakis N, Tooze SA, Yoshimori T, Yuan J, Yue Z, Zhong Q, Kroemer G Abstract Over the past two decades, the molecular machinery that underlies autophagic responses has been characterized with ever increasing precision in multiple model organisms. Moreover, it has become clear that autophagy and autophagy-related processes have profound implications for human pathophysiology. However, considerable confusion persists about the use of appropriate terms to indicate specific types of autophagy and some components of the autophagy machinery, which may have detrimental effects on the expansion of the field. Driven by the overt recognition of such a potential obstacle, a panel of leading experts in the field attempts here to define several autophagy-related terms based on specific biochemical features. The ultimate objective of this collaborative exchange is to formulate recommendations that facilitate the dissemination of knowledge within and outside the field of autophagy research. PMID: 28596378 [PubMed - indexed for MEDLINE]

Association of Radiomics and Metabolic Tumor Volumes in Radiation Treatment of Glioblastoma Multiforme.

Sat, 15/07/2017 - 13:41
Related Articles Association of Radiomics and Metabolic Tumor Volumes in Radiation Treatment of Glioblastoma Multiforme. Int J Radiat Oncol Biol Phys. 2017 Mar 01;97(3):586-595 Authors: Lopez CJ, Nagornaya N, Parra NA, Kwon D, Ishkanian F, Markoe AM, Maudsley A, Stoyanova R Abstract PURPOSE: To build a framework for investigation of the associations between imaging, clinical target volumes (CTVs), and metabolic tumor volumes (MTVs) features for better understanding of the underlying information in the CTVs and dependencies between these volumes. High-throughput extraction of imaging and metabolomic quantitative features from magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging of glioblastoma multiforme (GBM) results in tens of variables per patient. In radiation therapy of GBM the relevant metabolic tumor volumes (MTVs) are related to aberrant levels of N-acetyl aspartate (NAA) and choline (Cho). The corresponding clinical target volumes (CTVs) for radiation therapy are based on contrast-enhanced T1-weighted (CE-T1w) and T2-weighted (T2w)/fluid-attenuated inversion recovery MRI. METHODS AND MATERIALS: Necrotic portions, enhancing lesion, and edema were manually contoured on CE-T1w/T2w images for 17 GBM patients. Clinical target volumes and MTVs for NAA (MTVNAA) and Cho (MTVCho) were constructed. Imaging and metabolic features related to size, shape, and signal intensities of the volumes were extracted. Tumors were also scored categorically for 10 semantic imaging traits by a neuroradiologist. All features were investigated for redundancy. Two-way correlations between imaging and CTVs/MTVs features were visualized as heatmaps. Associations between MTVNAA and MTVCho and imaging features were studied using Spearman correlation. RESULTS: Forty-eight imaging features were extracted per patient. Half of the imaging traits were replaced with automatically extracted continuous variables. Twenty features were extracted from CTVs and MTVs. A series of semantic imaging traits were replaced with automatically extracted continuous variables. There were multiple (22) significant correlations of imaging measures with CTVs/MTVNAA, whereas there were only 6 with CTVs/MTVCho. CONCLUSIONS: A framework for investigation of codependencies between MRI and magnetic resonance spectroscopic imaging radiomic features and CTVs/MTVs has been established. The MTV for NAA was found to be closely associated with MRI volumes, whereas very few imaging features were related to MTVCho, indicating that Cho provides additional information to imaging. PMID: 28011044 [PubMed - indexed for MEDLINE]

The Past, Present, and (Possible) Future of Serologic Testing for Lyme Disease.

Sat, 15/07/2017 - 13:41
Related Articles The Past, Present, and (Possible) Future of Serologic Testing for Lyme Disease. J Clin Microbiol. 2016 May;54(5):1191-6 Authors: Theel ES Abstract Lyme disease prevails as the most commonly transmitted tick-borne infection in the United States, and serologic evaluation for antibodies to Borrelia burgdorferi remains the recommended modality for diagnosis. This review presents a brief historical perspective on the evolution of serologic assays for Lyme disease and provides a summary of the performance characteristics for the currently recommended two-tiered testing algorithm (TTTA). Additionally, a recently proposed alternative to the traditional TTTA is discussed, and novel methodologies, including immuno-PCR and metabolic profiling for Lyme disease, are outlined. PMID: 26865690 [PubMed - indexed for MEDLINE]

metabolomics; +31 new citations

Fri, 14/07/2017 - 13:01
31 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 2017/07/14PubMed 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 Profiling to Determine the Effect of Postmortem Aging on Color and Lipid Oxidative Stabilities of Different Bovine Muscles.

Thu, 13/07/2017 - 12:33
Metabolomics Profiling to Determine the Effect of Postmortem Aging on Color and Lipid Oxidative Stabilities of Different Bovine Muscles. J Agric Food Chem. 2017 Jul 12;: Authors: Ma D, Kim YHB, Cooper BR, Oh JH, Chun H, Choe J, Schoonmaker JP, Ajuwon KM, Min B Abstract The objective of this study was to identify the metabolites that could be associated with oxidative stability of aged bovine muscles. Three muscles (longissimus lumbrum (LL), semimembranosus (SM), and psoas major (PM)) from 7 beef carcasses at 1 day postmortem were divided into three sections and assigned to three aging periods (9, 16 and 23 days). While an increase in discoloration was found in all muscles with aging, LL was the most color/lipid oxidative stable, followed by SM and PM (P < 0.05). Lower myoglobin and non-heme iron contents were observed in LL compared to SM and PM (P < 0.05). The HPLC-ESI-MS based metabolomics analysis identified metabolites that were significantly responsive to aging and/or muscle type, such as acyl carnitines, free amino acids, nucleotides, nucleosides, and glucuronides. The results from the current study suggested that color and oxidative stability is inversely associated with aging, but is also muscle-specific. Further studies determining the exact role of the identified metabolites in color and oxidative stability of beef muscles should be warranted. PMID: 28700223 [PubMed - as supplied by publisher]

Proteomics and metabolomics in ageing research: from biomarkers to systems biology.

Thu, 13/07/2017 - 12:33
Related Articles Proteomics and metabolomics in ageing research: from biomarkers to systems biology. Essays Biochem. 2017 Jul 15;61(3):379-388 Authors: Hoffman JM, Lyu Y, Pletcher SD, Promislow DEL Abstract Age is the single greatest risk factor for a wide range of diseases, and as the mean age of human populations grows steadily older, the impact of this risk factor grows as well. Laboratory studies on the basic biology of ageing have shed light on numerous genetic pathways that have strong effects on lifespan. However, we still do not know the degree to which the pathways that affect ageing in the lab also influence variation in rates of ageing and age-related disease in human populations. Similarly, despite considerable effort, we have yet to identify reliable and reproducible 'biomarkers', which are predictors of one's biological as opposed to chronological age. One challenge lies in the enormous mechanistic distance between genotype and downstream ageing phenotypes. Here, we consider the power of studying 'endophenotypes' in the context of ageing. Endophenotypes are the various molecular domains that exist at intermediate levels of organization between the genotype and phenotype. We focus our attention specifically on proteins and metabolites. Proteomic and metabolomic profiling has the potential to help identify the underlying causal mechanisms that link genotype to phenotype. We present a brief review of proteomics and metabolomics in ageing research with a focus on the potential of a systems biology and network-centric perspective in geroscience. While network analyses to study ageing utilizing proteomics and metabolomics are in their infancy, they may be the powerful model needed to discover underlying biological processes that influence natural variation in ageing, age-related disease, and longevity. PMID: 28698311 [PubMed - in process]

metabolomics; +18 new citations

Wed, 12/07/2017 - 14:55
18 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 2017/07/12PubMed 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.

Microbial metabolites are associated with a high adherence to a Mediterranean dietary pattern using a (1)H-NMR-based untargeted metabolomics approach.

Tue, 11/07/2017 - 17:32
Microbial metabolites are associated with a high adherence to a Mediterranean dietary pattern using a (1)H-NMR-based untargeted metabolomics approach. J Nutr Biochem. 2017 Jun 07;48:36-43 Authors: Almanza-Aguilera E, Urpi-Sarda M, Llorach R, Vázquez-Fresno R, Garcia-Aloy M, Carmona F, Sanchez A, Madrid-Gambin F, Estruch R, Corella D, Andres-Lacueva C Abstract The study of biomarkers of dietary patterns including the Mediterranean diet (MedDiet) is scarce and could improve the assessment of these patterns. Moreover, it could provide a better understanding of health benefits of dietary patterns in nutritional epidemiology. We aimed to determine a robust and accurate biomarker associated with a high adherence to a MedDiet pattern that included dietary assessment and its biological effect. In this cross-sectional study, we included 56 and 63 individuals with high (H-MDA) and low (L-MDA) MedDiet adherence categories, respectively, all from the Prevención con Dieta Mediterránea trial. A (1)H-NMR-based untargeted metabolomics approach was applied to urine samples. Multivariate statistical analyses were conducted to determine the metabolite differences between groups. A stepwise logistic regression and receiver operating characteristic curves were used to build and evaluate the prediction model for H-MDA. Thirty-four metabolites were identified as discriminant between H-MDA and L-MDA. The fingerprint associated with H-MDA included higher excretion of proline betaine and phenylacetylglutamine, among others, and decreased amounts of metabolites related to glucose metabolism. Three microbial metabolites - phenylacetylglutamine, p-cresol and 4-hydroxyphenylacetate - were included in the prediction model of H-MDA (95% specificity, 95% sensitivity and 97% area under the curve). The model composed of microbial metabolites was the biomarker that defined high adherence to a Mediterranean dietary pattern. The overall metabolite profiling identified reflects the metabolic modulation produced by H-MDA. The proposed biomarker may be a better tool for assessing and aiding nutritional epidemiology in future associations between H-MDA and the prevention or amelioration of chronic diseases. PMID: 28692847 [PubMed - as supplied by publisher]

Systems biology of the modified branched Entner-Doudoroff pathway in Sulfolobus solfataricus.

Tue, 11/07/2017 - 17:32
Systems biology of the modified branched Entner-Doudoroff pathway in Sulfolobus solfataricus. PLoS One. 2017;12(7):e0180331 Authors: Figueiredo AS, Kouril T, Esser D, Haferkamp P, Wieloch P, Schomburg D, Ruoff P, Siebers B, Schaber J Abstract Sulfolobus solfataricus is a thermoacidophilic Archaeon that thrives in terrestrial hot springs (solfatares) with optimal growth at 80°C and pH 2-4. It catabolizes specific carbon sources, such as D-glucose, to pyruvate via the modified Entner-Doudoroff (ED) pathway. This pathway has two parallel branches, the semi-phosphorylative and the non-phosphorylative. However, the strategy of S.solfataricus to endure in such an extreme environment in terms of robustness and adaptation is not yet completely understood. Here, we present the first dynamic mathematical model of the ED pathway parameterized with quantitative experimental data. These data consist of enzyme activities of the branched pathway at 70°C and 80°C and of metabolomics data at the same temperatures for the wild type and for a metabolic engineered knockout of the semi-phosphorylative branch. We use the validated model to address two questions: 1. Is this system more robust to perturbations at its optimal growth temperature? 2. Is the ED robust to deletion and perturbations? We employed a systems biology approach to answer these questions and to gain further knowledge on the emergent properties of this biological system. Specifically, we applied deterministic and stochastic approaches to study the sensitivity and robustness of the system, respectively. The mathematical model we present here, shows that: 1. Steady state metabolite concentrations of the ED pathway are consistently more robust to stochastic internal perturbations at 80°C than at 70°C; 2. These metabolite concentrations are highly robust when faced with the knockout of either branch. Connected with this observation, these two branches show different properties at the level of metabolite production and flux control. These new results reveal how enzyme kinetics and metabolomics synergizes with mathematical modelling to unveil new systemic properties of the ED pathway in S.solfataricus in terms of its adaptation and robustness. PMID: 28692669 [PubMed - in process]

Biomarkers for predicting type 2 diabetes development-Can metabolomics improve on existing biomarkers?

Tue, 11/07/2017 - 17:32
Biomarkers for predicting type 2 diabetes development-Can metabolomics improve on existing biomarkers? PLoS One. 2017;12(7):e0177738 Authors: Savolainen O, Fagerberg B, Vendelbo Lind M, Sandberg AS, Ross AB, Bergström G Abstract AIM: The aim was to determine if metabolomics could be used to build a predictive model for type 2 diabetes (T2D) risk that would improve prediction of T2D over current risk markers. METHODS: Gas chromatography-tandem mass spectrometry metabolomics was used in a nested case-control study based on a screening sample of 64-year-old Caucasian women (n = 629). Candidate metabolic markers of T2D were identified in plasma obtained at baseline and the power to predict diabetes was tested in 69 incident cases occurring during 5.5 years follow-up. The metabolomics results were used as a standalone prediction model and in combination with established T2D predictive biomarkers for building eight T2D prediction models that were compared with each other based on their sensitivity and selectivity for predicting T2D. RESULTS: Established markers of T2D (impaired fasting glucose, impaired glucose tolerance, insulin resistance (HOMA), smoking, serum adiponectin)) alone, and in combination with metabolomics had the largest areas under the curve (AUC) (0.794 (95% confidence interval [0.738-0.850]) and 0.808 [0.749-0.867] respectively), with the standalone metabolomics model based on nine fasting plasma markers having a lower predictive power (0.657 [0.577-0.736]). Prediction based on non-blood based measures was 0.638 [0.565-0.711]). CONCLUSIONS: Established measures of T2D risk remain the best predictor of T2D risk in this population. Additional markers detected using metabolomics are likely related to these measures as they did not enhance the overall prediction in a combined model. PMID: 28692646 [PubMed - in process]

Comparison of fully-wettable RPLC stationary phases for LC-MS-based cellular metabolomics.

Tue, 11/07/2017 - 17:32
Comparison of fully-wettable RPLC stationary phases for LC-MS-based cellular metabolomics. Electrophoresis. 2017 Jul 10;: Authors: Si-Hung L, Causon TJ, Hann S Abstract Reversed-phase LC combined with high-resolution mass spectrometry (HRMS) is one of the most popular methods for cellular metabolomics studies. Due to the difficulties in analysing a wide range of polarities encountered in the metabolome, 100%-wettable reversed-phase materials are frequently used to maximise metabolome coverage within a single analysis. Packed with silica-based sub-3 μm diameter particles, these columns allow high separation efficiency and offer a reasonable compromise for metabolome coverage within a single analysis. While direct performance comparison can be made using classical chromatographic characterisation approaches, a comprehensive assessment of the column's performance for cellular metabolomics requires use of a full LC-HRMS workflow in order to reflect realistic study conditions used for cellular metabolomics. In this study, a comparison of several reversed-phase LC columns for metabolome analysis using such a dedicated workflow is presented. All columns were tested under the same analytical conditions on an LC-Time-of-Flight-MS (LC-TOFMS) platform using a variety of authentic metabolite standards and biotechnologically-relevant yeast cell extracts. Data on total workflow performance including retention behaviour, peak capacity, coverage, and molecular feature extraction repeatability from these columns are presented with consideration for both non-targeted screening and differential metabolomics workflows using authentic standards and Pichia pastoris cell extract samples. This article is protected by copyright. All rights reserved. PMID: 28691762 [PubMed - as supplied by publisher]

Nuclear magnetic resonance- and mass spectometry-based metabolomics to study maleic acid toxicity from repeated dose exposure in rats.

Tue, 11/07/2017 - 17:32
Nuclear magnetic resonance- and mass spectometry-based metabolomics to study maleic acid toxicity from repeated dose exposure in rats. J Appl Toxicol. 2017 Jul 10;: Authors: Wu C, Chen CH, Chen HC, Liang HJ, Chen ST, Lin WY, Wu KY, Chiang SY, Lin CY Abstract Maleic acid (MA), a chemical intermediate used in many consumer and industrial products, was intentionally adulterated in a variety of starch-based foods and instigated food safety incidents in Asia. We aim to elucidate possible mechanisms of MA toxicity after repeated exposure by (1) determining the changes of metabolic profile using (1) H nuclear magnetic resonance spectroscopy and multivariate analysis, and (2) investigating the occurrence of oxidative stress using liquid chromatography tandem mass spectrometry by using Sprague-Dawley rat urine samples. Adult male rats were subjected to a 28 day subchronic study (0, 6, 20 and 60 mg kg(-1) ) via oral gavage. Urine was collected twice a day on days 0, 7, 14, 21 and 28; organs underwent histopathological examination. Changes in body weight and relative kidney weights in medium- and high-dose groups were significantly different compared to controls. Morphological alterations were evident in the kidneys and liver. Metabolomic results demonstrated that MA exposure increases the urinary concentrations of 8-hydroxy-2'-deoxyguanosine, 8-nitroguanine and 8-iso-prostaglandin F2α ; levels of acetoacetate, hippurate, alanine and acetate demonstrated time- and dose-dependent variations in the treatment groups. Findings suggest that MA consumption escalates oxidative damage, membrane lipid destruction and disrupt energy metabolism. These aforementioned changes in biomarkers and endogenous metabolites elucidate and assist in characterizing the possible mechanisms by which MA induces nephro- and hepatotoxicity. PMID: 28691739 [PubMed - as supplied by publisher]

Integrated and global pseudotargeted metabolomics strategy applied to screening for quality control markers of Citrus TCMs.

Tue, 11/07/2017 - 17:32
Integrated and global pseudotargeted metabolomics strategy applied to screening for quality control markers of Citrus TCMs. Anal Bioanal Chem. 2017 Jul 10;: Authors: Shu Y, Liu Z, Zhao S, Song Z, He D, Wang M, Zeng H, Lu C, Lu A, Liu Y Abstract Traditional Chinese medicine (TCM) exerts its therapeutic effect in a holistic fashion with the synergistic function of multiple characteristic constituents. The holism philosophy of TCM is coincident with global and systematic theories of metabolomics. The proposed pseudotargeted metabolomics methodologies were employed for the establishment of reliable quality control markers for use in the screening strategy of TCMs. Pseudotargeted metabolomics integrates the advantages of both targeted and untargeted methods. In the present study, targeted metabolomics equipped with the gold standard RRLC-QqQ-MS method was employed for in vivo quantitative plasma pharmacochemistry study of characteristic prototypic constituents. Meanwhile, untargeted metabolomics using UHPLC-QE Orbitrap HRMS with better specificity and selectivity was employed for identification of untargeted metabolites in the complex plasma matrix. In all, 32 prototypic metabolites were quantitatively determined, and 66 biotransformed metabolites were convincingly identified after being orally administered with standard extracts of four labeled Citrus TCMs. The global absorption and metabolism process of complex TCMs was depicted in a systematic manner. PMID: 28691151 [PubMed - as supplied by publisher]

Comparison of Salt Tolerance in Soja Based on Metabolomics of Seedling Roots.

Tue, 11/07/2017 - 17:32
Comparison of Salt Tolerance in Soja Based on Metabolomics of Seedling Roots. Front Plant Sci. 2017;8:1101 Authors: Li M, Guo R, Jiao Y, Jin X, Zhang H, Shi L Abstract Soybean is an important economic crop that is continually threatened by abiotic stresses, especially salt stress. Wild soybean is an important germplasm resource for the breeding of cultivated soybean. The root system plays a very important role in plant salt tolerance. To explore the salt tolerance-related mechanisms among Soja, we have demonstrated the seedling roots' growth and metabolomics in wild soybean, semi-wild soybean, and cultivated soybean under two types of salt stress by using gas chromatography-mass spectrometry. We characterized 47 kinds of differential metabolites under neutral salt stress, and isoleucine, serine, l-allothreonine, glutamic acid, phenylalanine, asparagines, aspartic acid, pentadecanoic acid, lignoceric acid, oleic acid, galactose, tagatose, d-arabitol, dihydroxyacetone, 3-hydroxybutyric acid, and glucuronic acid increased significantly in the roots of wild soybean seedlings. However, these metabolites were suppressed in semi-wild and cultivated soybeans. Amino acid, fatty acid, sugars, and organic acid synthesis and the secondary metabolism of antioxidants increased significantly in the roots of wild soybean seedling. Under alkaline salt stress, wild soybean contained significantly higher amounts of proline, glutamic acid, aspartic acid, l-allothreonine, isoleucine, serine, alanine, arachidic acid, oleic acid, cis-gondoic acid, fumaric acid, l-malic acid, citric acid, malonic acid, gluconic acid, 5-methoxytryptamine, salicylic acid, and fluorene than semi-wild and cultivated soybeans. Our study demonstrated that carbon and nitrogen metabolism, and the tricarboxylic acid (TCA) cycle and receiver operating characteristics (especially the metabolism of phenolic substances) of the seedling roots were important to resisting salt stress and showed a regular decreasing trend from wild soybean to cultivated soybean. The metabolomics's changes were critical factors in the evolution of salt tolerance among Soja. This study provides new insights into salt tolerance in soybean, and presents quantitative parameters for a salt tolerant soybean breeding system, which is conducive to the rational use and protection of wild soybean resources. PMID: 28690628 [PubMed - in process]

Metabolite profiling in early clinical drug development: Current status and future prospects.

Tue, 11/07/2017 - 17:32
Metabolite profiling in early clinical drug development: Current status and future prospects. Expert Opin Drug Metab Toxicol. 2017 Jul 10;: Authors: Ufer M, Juif PE, Boof ML, Muehlan C, Dingemanse J PMID: 28689432 [PubMed - as supplied by publisher]

Factors affecting separation and detection of bile acids by liquid chromatography coupled with mass spectrometry in negative mode.

Mon, 10/07/2017 - 14:02
Factors affecting separation and detection of bile acids by liquid chromatography coupled with mass spectrometry in negative mode. Anal Bioanal Chem. 2017 Jul 08;: Authors: Yin S, Su M, Xie G, Li X, Wei R, Liu C, Lan K, Jia W Abstract Bile acids (BAs) are cholesterol metabolites with important biological functions. They undergo extensive host-gut microbial co-metabolisms during the enterohepatic circulation, creating a vast structural diversity and resulting in great challenges to separate and detect them. Based on the bioanalytical reports in the past decade, this work developed three chromatographic gradient methods to separate a total of 48 BA standards on an ethylene-bridged hybrid (BEH) C18 column and high-strength silica (HSS) T3 column and accordingly unraveled the factors affecting the separation and detection of them by liquid chromatography coupled with mass spectrometry (LC-MS). It was shown that both the acidity and ammonium levels in mobile phases reduced the electrospray ionization (ESI) of BAs as anions of [M-H](-), especially for those unconjugated ones without 12-hydroxylation. It was also found that the retention of taurine conjugates on the BEH C18 column was sensitive to the strength of formic acid and ammonium in mobile phases. By using the volatile buffers with an equivalent ammonium level as mobile phases, we comprehensively demonstrated the effects of the elution pH value on the retention behaviors of BAs on both the BEH C18 column and HSS T3 column. Based on the retention data acquired on a C18 column, we presented the ionization constants (pK a) of various BAs with the widest coverage beyond those of previous reports. When we made attempts to establish the structure-retention relationships (SRRs) of BAs, the lack of discriminative structural descriptors for BA stereoisomers emerged as the bottleneck problem. The methods and results presented in this work are especially useful for the development of reliable, sensitive, high-throughput, and robust LC-MS bioanalytical protocols for the quantitative metabolomic studies. Graphical Abstract Nonlinear curve fitting of capacity factors and elution pH value for the separation of common unconjugated bile acids. PMID: 28689325 [PubMed - as supplied by publisher]

Metabolic signature for severe cirrhosis with inflammation or hepatic encephalopathy: do we really face two different entities?

Mon, 10/07/2017 - 14:02
Metabolic signature for severe cirrhosis with inflammation or hepatic encephalopathy: do we really face two different entities? J Hepatol. 2017 Jul 05;: Authors: Weiss N, Colsch B, Fenaille F, Junot C, Thabut D PMID: 28688802 [PubMed - as supplied by publisher]

Preparation and evaluation of mesoporous silica layers on radially elongated pillars.

Mon, 10/07/2017 - 14:02
Preparation and evaluation of mesoporous silica layers on radially elongated pillars. J Chromatogr A. 2017 Jun 24;: Authors: Futagami S, Hara T, Ottevaere H, Baron GV, Desmet G, De Malsche W Abstract The present paper describes the application of a sol-gel procedure on radially elongated pillars (REPs) using tetramethoxysilane and methyltrimethoxysilane. After octadecylsilylation, the quality of the porous layered REP (PLREP) columns was evaluated by in-situ determination of migration velocities and band broadening of coumarin dyes with fluorescence microscopy in reversed-phase liquid chromatography. Based on the increase in retention due to the sol-gel process, an increase in accessible specific surface by a factor of 112 was observed. Argon physisorption measurements on bulk monoliths prepared with the same method revealed a predominant pore size of 91Å. Plate heights as low as 0.4-0.8μm (k=0-1.97) could be obtained thanks to the very low dispersion of the REP format and to the fact that the applied silica layer was conformally and uniformly deposited on the flow-through channels. A kinetic plot analysis demonstrated that the studied PLREP column will deliver more theoretical plates per unit of time than a 5μm core shell packed bed when more than 1.0×10(4) theoretical plates are required. PMID: 28688720 [PubMed - as supplied by publisher]

metabolomics; +17 new citations

Sat, 08/07/2017 - 13:30
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 2017/07/08PubMed 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.

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