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 17 min ago

Targeted and Untargeted Metabolomics to Explore the Bioavailability of the Secoiridoids from a Seed/Fruit Extract (Fraxinus angustifolia Vahl) in Human Healthy Volunteers: A Preliminary Study.

Wed, 23/12/2015 - 13:36
Targeted and Untargeted Metabolomics to Explore the Bioavailability of the Secoiridoids from a Seed/Fruit Extract (Fraxinus angustifolia Vahl) in Human Healthy Volunteers: A Preliminary Study. Molecules. 2015;20(12):22202-19 Authors: García-Villalba R, Tomás-Barberán FA, Fança-Berthon P, Roller M, Zafrilla P, Issaly N, García-Conesa MT Abstract The bark, seeds, fruits and leaves of the genus Fraxinus (Oleaceae) which contain a wide range of phytochemicals, mostly secoiridoid glucosides, have been widely used in folk medicine against a number of ailments, yet little is known about the metabolism and uptake of the major Fraxinus components. The aim of this work was to advance in the knowledge on the bioavailability of the secoiridoids present in a Fraxinus angustifolia Vahl seed/fruit extract using both targeted and untargeted metabolomic analyses. Plasma and urine samples from nine healthy volunteers were taken at specific time intervals following the intake of the extract and analyzed by UPLC-ESI-QTOF. Predicted metabolites such as tyrosol and ligstroside-aglycone glucuronides and sulfates were detected at low intensity. These compounds reached peak plasma levels 2 h after the intake and exhibited high variability among the participants. The ligstroside-aglycone conjugates may be considered as potential biomarkers of the Fraxinus secoiridoids intake. Using the untargeted approach we additionally detected phenolic conjugates identified as ferulic acid and caffeic acid sulfates, as well as hydroxybenzyl and hydroxyphenylacetaldehyde sulfate derivatives which support further metabolism of the secoiridoids by phase I and (or) microbial enzymes. Overall, the results of this study suggest low uptake of intact secoiridoids from a Fraxinus angustifolia Vahl extract in healthy human volunteers and metabolic conversion by esterases, glycosidases, and phase II sulfo- and glucuronosyl transferases to form smaller conjugated derivatives. PMID: 26690403 [PubMed - in process]

Effective Estimation of Dynamic Metabolic Fluxes Using (13)C Labeling and Piecewise Affine Approximation: From Theory to Practical Applicability.

Wed, 23/12/2015 - 13:36
Effective Estimation of Dynamic Metabolic Fluxes Using (13)C Labeling and Piecewise Affine Approximation: From Theory to Practical Applicability. Metabolites. 2015;5(4):697-719 Authors: Schumacher R, Wahl SA Abstract The design of microbial production processes relies on rational choices for metabolic engineering of the production host and the process conditions. These require a systematic and quantitative understanding of cellular regulation. Therefore, a novel method for dynamic flux identification using quantitative metabolomics and (13)C labeling to identify piecewise-affine (PWA) flux functions has been described recently. Obtaining flux estimates nevertheless still required frequent manual reinitalization to obtain a good reproduction of the experimental data and, moreover, did not optimize on all observables simultaneously (metabolites and isotopomer concentrations). In our contribution we focus on measures to achieve faster and robust dynamic flux estimation which leads to a high dimensional parameter estimation problem. Specifically, we address the following challenges within the PWA problem formulation: (1) Fast selection of sufficient domains for the PWA flux functions, (2) Control of over-fitting in the concentration space using shape-prescriptive modeling and (3) robust and efficient implementation of the parameter estimation using the hybrid implicit filtering algorithm. With the improvements we significantly speed up the convergence by efficiently exploiting that the optimization problem is partly linear. This allows application to larger-scale metabolic networks and demonstrates that the proposed approach is not purely theoretical, but also applicable in practice. PMID: 26690237 [PubMed]

Sex-Dependent Depression-Like Behavior Induced by Respiratory Administration of Aluminum Oxide Nanoparticles.

Wed, 23/12/2015 - 13:36
Sex-Dependent Depression-Like Behavior Induced by Respiratory Administration of Aluminum Oxide Nanoparticles. Int J Environ Res Public Health. 2015;12(12):15692-705 Authors: Zhang X, Xu Y, Zhou L, Zhang C, Meng Q, Wu S, Wang S, Ding Z, Chen X, Li X, Chen R Abstract Ultrafine aluminum oxide, which are abundant in ambient and involved occupational environments, are associated with neurobehavioral alterations. However, few studies have focused on the effect of sex differences following exposure to environmental Al₂O₃ ultrafine particles. In the present study, male and female mice were exposed to Al₂O₃ nanoparticles (NPs) through a respiratory route. Only the female mice showed depression-like behavior. Although no obvious pathological changes were observed in mice brain tissues, the neurotransmitter and voltage-gated ion channel related gene expression, as well as the small molecule metabolites in the cerebral cortex, were differentially modulated between male and female mice. Both mental disorder-involved gene expression levels and metabolomics analysis results strongly suggested that glutamate pathways were implicated in sex differentiation induced by Al₂O₃ NPs. Results demonstrated the potential mechanism of environmental ultrafine particle-induced depression-like behavior and the importance of sex dimorphism in the toxic research of environmental chemicals. PMID: 26690197 [PubMed - in process]

The anti-atherosclerotic effect of tanshinol borneol ester using fecal metabolomics based on liquid chromatography-mass spectrometry.

Wed, 23/12/2015 - 13:36
The anti-atherosclerotic effect of tanshinol borneol ester using fecal metabolomics based on liquid chromatography-mass spectrometry. Analyst. 2015 Dec 22; Authors: Jia P, Wang S, Xiao C, Yang L, Chen Y, Jiang W, Zheng X, Zhao G, Zang W, Zheng X Abstract Tanshinol borneol ester (DBZ) is a novel experimental compound that consists of two chemical structural units from danshensu and borneol. It exhibits efficacious anti-ischemic and anti-atherosclerosis activities in rats. A fecal metabolomics based on Liquid Chromatography-Mass Spectrometry combined with clinical histopathology and blood lipid estimation was employed to assess the efficacy and the metabolic changes caused by administration of DBZ in atherosclerotic rats. There were the typical pathological features of atherosclerosis and significantly increased levels of TC, TG and LDL-C in the atherosclerotic rat group. Nevertheless, atherosclerotic rats administered both DBZ (at a dose of 40 mg kg(-1)) and simvastatin (at a dose of 20 mg kg(-1)) showed good therapeutic effects. The results of the metabolomics studies showed that 55 differential metabolites such as sebacic acid, enterodiol, nonanedioic acid, dodecanedioic acid, cholic acid, 13(S)-HPODE, deoxycholic acid, some phosphatidylglycerol and phosphatidic acids were found, indicating that abnormal metabolism occurred in the pathways of fatty acid oxidation, linoleic acid metabolism, bile acid biosynthesis and glycerophospholipid metabolism in atherosclerotic rats. Compared to those in the model group, the contents of 41 differential metabolites showed a tendency to recover to a healthy level after DBZ administration. Metabolomics studies suggested that DBZ exhibited good treatment efficacy against atherosclerosis by adjusting disturbed metabolic pathways related to atherosclerosis. This study could provide an experimental basis for DBZ's application to act as a candidate drug with anti-atherosclerosis activity. PMID: 26689835 [PubMed - as supplied by publisher]

Principal component analysis of molecularly-based signals from infant formula contaminations using LC-MS and NMR in foodomics.

Wed, 23/12/2015 - 13:36
Principal component analysis of molecularly-based signals from infant formula contaminations using LC-MS and NMR in foodomics. J Sci Food Agric. 2015 Dec 22; Authors: Inoue K, Tanada C, Hosoya T, Yoshida S, Akiba T, Min JZ, Todoroki K, Yamano Y, Kumazawa S, Toyo'oka T Abstract BACKGROUND: The challenge in developing analytical assessment of unexpected excess contaminations in infant formula has been the most significant project to address the widespread issue of food safety and security. Foodomics based on metabolomics techniques provides powerful tools for the detection of tampering cases with intentional contaminations. However, the safety and risk assessments of infant formula to reveal not only the targeted presences of toxic chemicals, but also molecular changes involving unexpected contaminations, have not been reported. In this study, a huge amount of raw molecularly-based signals from infant formula was analyzed using the reversed phase and hydrophilic interaction chromatography with time-of-flight MS (LC-MS) and (1) H-nuclear magnetic resonance (NMR) and then processed by a principal component analysis (PCA). RESULTS: PCA plots visualized signature trends in the complex signal-data batches from each excess contamination of detectable chemicals by LC-MS and NMR. These trends in the different batches from a portion of excess chemical contaminations such as pesticides, melamine and heavy-metals and out-of-date product can be visualized from spectrally-discriminated infant formula samples. CONCLUSION: PCA plots provide possible attempts to maximize the covariance between the stable lot-to-lot uniformity and excess exogenous contaminations and/or degradation to discriminate against the molecularly-based signals from infant formulas. PMID: 26689721 [PubMed - as supplied by publisher]

Mass Spectrometry-Based Metabolomics: A Practical Guide : Sastia Prama Putri and Eiichiro Fukusaki, Editors CRC Press, Taylor & Francis Group, Boca Raton, FL ISBN: 978-1-4822-2376-7 2014, Hardcover, $112 US, 294 pages.

Wed, 23/12/2015 - 13:36
Mass Spectrometry-Based Metabolomics: A Practical Guide : Sastia Prama Putri and Eiichiro Fukusaki, Editors CRC Press, Taylor & Francis Group, Boca Raton, FL ISBN: 978-1-4822-2376-7 2014, Hardcover, $112 US, 294 pages. J Am Soc Mass Spectrom. 2016 Jan;27(1):1-2 Authors: Shriver LP PMID: 26689410 [PubMed - in process]

Discrimination of Polygonatum species and identification of novel markers using 1H NMR and UPLC/Q-TOF MS based metabolite profiling.

Wed, 23/12/2015 - 13:36
Discrimination of Polygonatum species and identification of novel markers using 1H NMR and UPLC/Q-TOF MS based metabolite profiling. J Sci Food Agric. 2015 Dec 22; Authors: Lee MY, Moon BC, Kwon YK, Jung Y, Oh TK, Hwang GS Abstract BACKGROUND: Rhizomes of Polygonatum species are commonly used as herbal supplements in Asia. They have different medicinal effects by species but have been misused and mixed due to their similar taste and smell. Therefore, accurate and reliable analytical methods to discriminate between Polygonatum species are required. RESULTS: In this study, global and targeted metabolite profiling using (1) H nuclear magnetic resonance spectroscopy ((1) H NMR) and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) were applied to discriminate between different Polygonatum species. Partial least squared discriminant analysis (PLS-DA) models were used to classify and predict species of Polygonatum. Cross-validation derived from PLS-DA revealed good predictive accuracy. Polygonatum species were classified into unique patterns based on K-means cluster analysis. Compound 4-hydrobenzoic acid and trigonelline were identified as novel marker compounds and quantified accurately. CONCLUSION: Our results demonstrate that metabolite profiling approaches coupled with chemometric analysis can be used to classify and discriminate between different species of various herbal medicines. PMID: 26689164 [PubMed - as supplied by publisher]

Trichome differentiation on leaf primordia of Helianthus annuus (Asteraceae): morphology, gene expression and metabolite profile.

Wed, 23/12/2015 - 13:36
Related Articles Trichome differentiation on leaf primordia of Helianthus annuus (Asteraceae): morphology, gene expression and metabolite profile. Planta. 2015 Apr;241(4):837-46 Authors: Aschenbrenner AK, Amrehn E, Bechtel L, Spring O Abstract MAIN CONCLUSION: Sunflower trichomes fully develop on embryonic plumula within 3 days after start of germination. Toxic sesquiterpene lactones are produced immediately thereafter thus protecting the apical bud of the seedling against herbivory. Helianthus annuus harbors non-glandular and two different types of multicellular glandular trichomes, namely the biseriate capitate glandular trichomes and the uniseriate linear glandular trichomes. The development of capitate glandular trichomes is well known from anther tips on sunflower disk florets, but not from leaves and no information is yet available on the development of the linear glandular trichomes. Scanning electron microscopy of sunflower seedlings unravelled that within the first 40 h of seed germination all three types of trichomes started to emerge on primordia of the first true leaves. Within the following 20-30 h trichomes developed from trichoblasts to fully differentiated hairs. Gene expression studies showed that genes involved in the trichome-based sesquiterpene lactone formation were up-regulated between 72 and 96 h after start of germination. Metabolite profiling with HPLC confirmed the synthesis of sesquiterpene lactones which may contribute to protect the germinating seedlings from herbivory. The study has shown that sunflower leaf primordia can serve as a fast and easy to handle model system for the investigation of trichome development in Asteraceae. PMID: 25515194 [PubMed - indexed for MEDLINE]

Effect of breadmaking process on in vitro gut microbiota parameters in irritable bowel syndrome.

Wed, 23/12/2015 - 13:36
Related Articles Effect of breadmaking process on in vitro gut microbiota parameters in irritable bowel syndrome. PLoS One. 2014;9(10):e111225 Authors: Costabile A, Santarelli S, Claus SP, Sanderson J, Hudspith BN, Brostoff J, Ward JL, Lovegrove A, Shewry PR, Jones HE, Whitley AM, Gibson GR Abstract A variety of foods have been implicated in symptoms of patients with Irritable Bowel Syndrome (IBS) but wheat products are most frequently cited by patients as a trigger. Our aim was to investigate the effects of breads, which were fermented for different lengths of time, on the colonic microbiota using in vitro batch culture experiments. A set of in vitro anaerobic culture systems were run over a period of 24 h using faeces from 3 different IBS donors (Rome Criteria-mainly constipated) and 3 healthy donors. Changes in gut microbiota during a time course were identified by fluorescence in situ hybridisation (FISH), whilst the small-molecular weight metabolomic profile was determined by NMR analysis. Gas production was separately investigated in non pH-controlled, 36 h batch culture experiments. Numbers of bifidobacteria were higher in healthy subjects compared to IBS donors. In addition, the healthy donors showed a significant increase in bifidobacteria (P<0.005) after 8 h of fermentation of a bread produced using a sourdough process (type C) compared to breads produced with commercial yeasted dough (type B) and no time fermentation (Chorleywood Breadmaking process) (type A). A significant decrease of δ-Proteobacteria and most Gemmatimonadetes species was observed after 24 h fermentation of type C bread in both IBS and healthy donors. In general, IBS donors showed higher rates of gas production compared to healthy donors. Rates of gas production for type A and conventional long fermentation (type B) breads were almost identical in IBS and healthy donors. Sourdough bread produced significantly lower cumulative gas after 15 h fermentation as compared to type A and B breads in IBS donors but not in the healthy controls. In conclusion, breads fermented by the traditional long fermentation and sourdough are less likely to lead to IBS symptoms compared to bread made using the Chorleywood Breadmaking Process. PMID: 25356771 [PubMed - indexed for MEDLINE]

Mass spectrometry-based metabolite profiling in the mouse liver following exposure to ultraviolet B radiation.

Wed, 23/12/2015 - 13:36
Related Articles Mass spectrometry-based metabolite profiling in the mouse liver following exposure to ultraviolet B radiation. PLoS One. 2014;9(10):e109479 Authors: Park HM, Shon JC, Lee MY, Liu KH, Kim JK, Lee SJ, Lee CH Abstract Although many studies have been performed on the effects of ultraviolet (UV) radiation on the skin, only a limited number of reports have investigated these effects on non-skin tissue. This study aimed to describe the metabolite changes in the liver of hairless mice following chronic exposure to UVB radiation. We did not observe significant macroscopic changes or alterations in hepatic cholesterol and triglyceride levels in the liver of UVB-irradiated mice, compared with those for normal mice. In this study, we detected hepatic metabolite changes by UVB exposure and identified several amino acids, fatty acids, nucleosides, carbohydrates, phospholipids, lysophospholipids, and taurine-conjugated cholic acids as candidate biomarkers in response to UVB radiation in the mouse liver by using various mass spectrometry (MS)-based metabolite profiling including ultra-performance liquid chromatography-quadrupole time-of-flight (TOF)-MS, gas chromatography-TOF-MS and nanomate LTQ-MS. Glutamine exhibited the most dramatic change with a 5-fold increase in quantity. The results from altering several types of metabolites suggest that chronic UVB irradiation may impact significantly on major hepatic metabolism processes, despite the fact that the liver is not directly exposed to UVB radiation. MS-based metabolomic approach for determining regulatory hepatic metabolites following UV irradiation will provide a better understanding of the relationship between internal organs and UV light. PMID: 25275468 [PubMed - indexed for MEDLINE]

Gestational dating by metabolic profile at birth: A California cohort study.

Tue, 22/12/2015 - 12:09
Gestational dating by metabolic profile at birth: A California cohort study. Am J Obstet Gynecol. 2015 Dec 11; Authors: Jelliffe-Pawlowski LL, Norton ME, Baer RJ, Santos N, Rutherford GW Abstract BACKGROUND: Accurate gestational dating is a critical component of obstetric and newborn care. In the absence of early ultrasound, many clinicians rely on less accurate measures, such as last menstrual period or symphysis-fundal height during pregnancy, or Dubowitz scoring or the Ballard (or New Ballard) method at birth. These measures often under- or over-estimate gestational age and can lead to misclassification of babies as born preterm, which has both short- and long-term clinical care and public health implications. OBJECTIVE: To evaluate whether metabolic markers in newborns measured as part of routine screening for treatable inborn errors of metabolism can be used to develop a population-level metabolic gestational dating algorithm that is robust despite intrauterine growth restriction and can be used when fetal ultrasound dating is not available. We focused specifically on the ability of these markers to differentiate preterm births (<37 weeks) from term births and to assign a specific gestational age in the preterm birth group. STUDY DESIGN: We evaluated a cohort of 729,503 singleton newborns with a California birth in 2005 through 2011 who had routine newborn metabolic screening and fetal ultrasound dating at 11 to 20 weeks' gestation. Using training and testing subsets (divided in a ratio of 3 to 1) we evaluated the association between preterm birth, target newborn characteristics, acylcarnitines, amino acids, thyroid stimulating hormone, 17-hydroxyprogesterone, and galactose-1-phosphate-uridyl-transferase. We used multivariate backward stepwise regression to test for associations and linear discriminate analyses (LDA) to create a linear function for preterm birth and to assign a specific week of gestation. We used sensitivity, specificity, and positive predictive value to evaluate the performance of linear functions. RESULTS: Along with birth weight and infant age at test, we included 35 of the 51 metabolic markers measured in the final multivariate model comparing preterm and term births. Using a LDA-derived linear function, we were able to sort preterm and term births accurately with sensitivities and specificities of 95% or more in both the training and testing subsets. Assignment of a specific week of gestation in those identified as preterm births resulted in the correct assignment of week +/-2 weeks in 89.8% of all newborns in the training and 91.7% of those in the testing subset. When preterm birth rates were modeled using the metabolic dating algorithm compared to fetal ultrasound, preterm-birth rates were 7.15% versus 6.11% in the training subset and 7.31% versus 6.25% in the testing subset. CONCLUSION: When considered in combination with birth weight and hours of age at test, metabolic profile evaluated within eight days of birth appears to be a useful measure of preterm birth and, among those born preterm, of specific week of gestation +/-2 weeks. Dating by metabolic profile may be useful in instances where there is no fetal ultrasound due to lack of availability or late entry into care. PMID: 26688490 [PubMed - as supplied by publisher]

Integrative drug efficacy assessment of Danggui and European Danggui using NMR-based metabolomics.

Tue, 22/12/2015 - 12:09
Integrative drug efficacy assessment of Danggui and European Danggui using NMR-based metabolomics. J Pharm Biomed Anal. 2015 Dec 3;120:1-9 Authors: Zhang ZZ, Fan ML, Hao X, Qin XM, Li ZY Abstract Danggui (DG) is a commonly used herbal drug in traditional Chinese medicine, and usually adulterated with European Danggui (EDG) due to the increasing demand. In present study, global metabolic profiling with NMR coupled with integrative drug efficacy evaluation methods was performed to compare and discover underlying blood-enriching regulation mechanisms of DG and EDG on blood deficiency rats induced by acetyl phenylhydrazine (APH). Totally, the contents of 12 key metabolites in serum and 4 in urine of DG group, 7 in serum and 4 in urine of EDG group were significantly reversed in comparison with model group. DG was more effective than EDG as revealed by the relative distance, efficacy index and similarity analysis. The metabolism pathways analysis showed that the better effect of DG maybe related with the regulatory effect on valine, leucine and isoleucine biosynthesis, synthesis and degradation of ketone bodies, glycine, serine and threonine metabolism, as well as nicotinate and nicotinamide metabolism. The results presented here showed that metabolomic coupled with efficacy index and similarity analysis made it possible to disclose the subtle biological difference between DG and EDG, which highlight the potential of metabolomic approach to quantitatively compare the pharmacological effect of the herbal drugs. PMID: 26686769 [PubMed - as supplied by publisher]

The role of endothelial mechanosensitive genes in atherosclerosis and omics approaches.

Tue, 22/12/2015 - 12:09
The role of endothelial mechanosensitive genes in atherosclerosis and omics approaches. Arch Biochem Biophys. 2015 Dec 10; Authors: Simmons RD, Kumar S, Jo H Abstract Atherosclerosis is the leading cause of morbidity and mortality in the U.S., and is a multifactorial disease that preferentially occurs in regions of the arterial tree exposed to disturbed blood flow. The detailed mechanisms by which d-flow induces atherosclerosis involve changes in the expression of genes, epigenetic patterns, and metabolites of multiple vascular cells, especially endothelial cells. This review presents an overview of endothelial mechanobiology and its relation to the pathogenesis of atherosclerosis with special reference to the anatomy of the artery and the underlying fluid mechanics, followed by a discussion of a variety of experimental models to study the role of fluid mechanics and atherosclerosis. Various in vitro and in vivo models to study the role of flow in endothelial biology and pathobiology are discussed in this review. Furthermore, strategies used for the global profiling of the genome, transcriptome, miRNA-nome, DNA methylome, and metabolome, as they are important to define the biological and pathophysiological mechanisms of atherosclerosis. These "omics" approaches, especially those which derive data based on a single animal model, provide unprecedented opportunities to not only better understand the pathophysiology of atherosclerosis development in a holistic and integrative manner, but also to identify novel molecular and diagnostic targets. PMID: 26686737 [PubMed - as supplied by publisher]

Modulation of genetic clusters for synthesis of bioactive molecules in fungal endophytes: A review.

Tue, 22/12/2015 - 12:09
Modulation of genetic clusters for synthesis of bioactive molecules in fungal endophytes: A review. Microbiol Res. 2016 Jan;182:125-40 Authors: Deepika VB, Murali TS, Satyamoorthy K Abstract Novel drugs with unique and targeted mode of action are very much need of the hour to treat and manage severe multidrug infections and other life-threatening complications. Though natural molecules have proved to be effective and environmentally safe, the relative paucity of discovery of new drugs has forced us to lean towards synthetic chemistry for developing novel drug molecules. Plants and microbes are the major resources that we rely upon in our pursuit towards discovery of novel compounds of pharmacological importance with less toxicity. Endophytes, an eclectic group of microbes having the potential to chemically bridge the gap between plants and microbes, have attracted the most attention due to their relatively high metabolic versatility. Since continuous large scale supply of major metabolites from microfungi and especially endophytes is severely impeded by the phenomenon of attenuation in axenic cultures, the major challenge is to understand the regulatory mechanisms in operation that drive the expression of metabolic gene clusters of pharmaceutical importance. This review is focused on the major regulatory elements that operate in filamentous fungi and various combinatorial multi-disciplinary approaches involving bioinformatics, molecular biology, and metabolomics that could aid in large scale synthesis of important lead molecules. PMID: 26686621 [PubMed - in process]

Neurometabolic roles of ApoE and Ldl-R in mouse brain.

Tue, 22/12/2015 - 12:09
Neurometabolic roles of ApoE and Ldl-R in mouse brain. J Bioenerg Biomembr. 2015 Dec 21; Authors: Lee J, Choi J, Wong GW, Wolfgang MJ Abstract Polymorphisms in ApoE are highly correlated with the progression of neurodegenerative disease, in particular Alzheimer's disease. Little is known, however, about the role of ApoE or cholesterol metabolism on brain neurochemistry in general. To better understand the role of lipoprotein and cholesterol metabolism in the brain, we profiled 6 and 12-week old Apoe KO and Ldlr KO mouse models via unbiased metabolomics to determine which metabolites were affected at an early age to identify those that may play a role in triggering pathology later in life. Steady-state metabolomics revealed only subtle differences among Apoe KO, Ldlr KO and WT mouse brains. Ldlr KO mice exhibited alterations in metabolites involved in neurotransmitter, amino acid and cholesterol metabolism. In contrast, Apoe KO mice only showed subtle changes in amino acid and neurotransmitter metabolism. These subtle changes in a broad range of metabolites indicate that ApoE and Ldl-R alone may not play a significant role in these mouse models at an early age, but instead require the cumulative effect from different pathways that lead to dysfunction at a much later stage of life. PMID: 26686234 [PubMed - as supplied by publisher]

Lactobacillus and Leuconostoc volatilomes in cheese conditions.

Tue, 22/12/2015 - 12:09
Lactobacillus and Leuconostoc volatilomes in cheese conditions. Appl Microbiol Biotechnol. 2015 Dec 19; Authors: Pogačić T, Maillard MB, Leclerc A, Hervé C, Chuat V, Valence F, Thierry A Abstract New strains are desirable to diversify flavour of fermented dairy products. The objective of this study was to evaluate the potential of Leuconostoc spp. and Lactobacillus spp. in the production of aroma compounds by metabolic fingerprints of volatiles. Eighteen strains, including five Lactobacillus species (Lactobacillus fermentum, Lactobacillus helveticus, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus sakei) and three Leuconostoc species (Leuconostoc citreum, Leuconostoc lactis, and Leuconostoc mesenteroides) were incubated for 5 weeks in a curd-based slurry medium under conditions mimicking cheese ripening. Populations were enumerated and volatile compounds were analysed by headspace trap gas chromatography-mass spectrometry (GC-MS). A metabolomics approach followed by multivariate statistical analysis was applied for data processing and analysis. In total, 12 alcohols, 10 aldehydes, 7 esters, 11 ketones, 5 acids and 2 sulphur compounds were identified. Very large differences in concentration of volatile compounds between the highest producing strains and the control medium were observed in particular for diacetyl, 2-butanol, ethyl acetate, 3-methylbutanol, 3-methylbutanoic acid and 2-methylbutanoic acid. Some of the characterized strains demonstrated an interesting aromatizing potential to be used as adjunct culture. PMID: 26685674 [PubMed - as supplied by publisher]

Succinylome analysis reveals the involvement of lysine succinylation in metabolism in pathogenic Mycobacterium tuberculosis.

Tue, 22/12/2015 - 12:09
Related Articles Succinylome analysis reveals the involvement of lysine succinylation in metabolism in pathogenic Mycobacterium tuberculosis. Mol Cell Proteomics. 2015 Apr;14(4):796-811 Authors: Yang M, Wang Y, Chen Y, Cheng Z, Gu J, Deng J, Bi L, Chen C, Mo R, Wang X, Ge F Abstract Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis, remains one of the most prevalent human pathogens and a major cause of mortality worldwide. Metabolic network is a central mediator and defining feature of the pathogenicity of Mtb. Increasing evidence suggests that lysine succinylation dynamically regulates enzymes in carbon metabolism in both bacteria and human cells; however, its extent and function in Mtb remain unexplored. Here, we performed a global succinylome analysis of the virulent Mtb strain H37Rv by using high accuracy nano-LC-MS/MS in combination with the enrichment of succinylated peptides from digested cell lysates and subsequent peptide identification. In total, 1545 lysine succinylation sites on 626 proteins were identified in this pathogen. The identified succinylated proteins are involved in various biological processes and a large proportion of the succinylation sites are present on proteins in the central metabolism pathway. Site-specific mutations showed that succinylation is a negative regulatory modification on the enzymatic activity of acetyl-CoA synthetase. Molecular dynamics simulations demonstrated that succinylation affects the conformational stability of acetyl-CoA synthetase, which is critical for its enzymatic activity. Further functional studies showed that CobB, a sirtuin-like deacetylase in Mtb, functions as a desuccinylase of acetyl-CoA synthetase in in vitro assays. Together, our findings reveal widespread roles for lysine succinylation in regulating metabolism and diverse processes in Mtb. Our data provide a rich resource for functional analyses of lysine succinylation and facilitate the dissection of metabolic networks in this life-threatening pathogen. PMID: 25605462 [PubMed - indexed for MEDLINE]

Douglas-fir seedlings exhibit metabolic responses to increased temperature and atmospheric drought.

Tue, 22/12/2015 - 12:09
Related Articles Douglas-fir seedlings exhibit metabolic responses to increased temperature and atmospheric drought. PLoS One. 2014;9(12):e114165 Authors: Jansen K, Du B, Kayler Z, Siegwolf R, Ensminger I, Rennenberg H, Kammerer B, Jaeger C, Schaub M, Kreuzwieser J, Gessler A Abstract In the future, periods of strongly increased temperature in concert with drought (heat waves) will have potentially detrimental effects on trees and forests in Central Europe. Norway spruce might be at risk in the future climate of Central Europe. However, Douglas-fir is often discussed as an alternative for the drought and heat sensitive Norway spruce, because some provenances are considered to be well adapted to drier and warmer conditions. In this study, we identified the physiological and growth responses of seedlings from two different Douglas-fir provenances to increased temperature and atmospheric drought during a period of 92 days. We analysed (i) plant biomass, (ii) carbon stable isotope composition as an indicator for time integrated intrinsic water use efficiency, (iii) apparent respiratory carbon isotope fractionation as well as (iv) the profile of polar low molecular metabolites. Plant biomass was only slightly affected by increased temperatures and atmospheric drought but the more negative apparent respiratory fractionation indicated a temperature-dependent decrease in the commitment of substrate to the tricarboxylic acid cycle. The metabolite profile revealed that the simulated heat wave induced a switch in stress protecting compounds from proline to polyols. We conclude that metabolic acclimation successfully contributes to maintain functioning and physiological activity in seedlings of both Douglas-fir provenances under conditions that are expected during heat waves (i.e. elevated temperatures and atmospheric drought). Douglas-fir might be a potentially important tree species for forestry in Central Europe under changing climatic conditions. PMID: 25436455 [PubMed - indexed for MEDLINE]

ALLocator: an interactive web platform for the analysis of metabolomic LC-ESI-MS datasets, enabling semi-automated, user-revised compound annotation and mass isotopomer ratio analysis.

Tue, 22/12/2015 - 12:09
Related Articles ALLocator: an interactive web platform for the analysis of metabolomic LC-ESI-MS datasets, enabling semi-automated, user-revised compound annotation and mass isotopomer ratio analysis. PLoS One. 2014;9(11):e113909 Authors: Kessler N, Walter F, Persicke M, Albaum SP, Kalinowski J, Goesmann A, Niehaus K, Nattkemper TW Abstract Adduct formation, fragmentation events and matrix effects impose special challenges to the identification and quantitation of metabolites in LC-ESI-MS datasets. An important step in compound identification is the deconvolution of mass signals. During this processing step, peaks representing adducts, fragments, and isotopologues of the same analyte are allocated to a distinct group, in order to separate peaks from coeluting compounds. From these peak groups, neutral masses and pseudo spectra are derived and used for metabolite identification via mass decomposition and database matching. Quantitation of metabolites is hampered by matrix effects and nonlinear responses in LC-ESI-MS measurements. A common approach to correct for these effects is the addition of a U-13C-labeled internal standard and the calculation of mass isotopomer ratios for each metabolite. Here we present a new web-platform for the analysis of LC-ESI-MS experiments. ALLocator covers the workflow from raw data processing to metabolite identification and mass isotopomer ratio analysis. The integrated processing pipeline for spectra deconvolution "ALLocatorSD" generates pseudo spectra and automatically identifies peaks emerging from the U-13C-labeled internal standard. Information from the latter improves mass decomposition and annotation of neutral losses. ALLocator provides an interactive and dynamic interface to explore and enhance the results in depth. Pseudo spectra of identified metabolites can be stored in user- and method-specific reference lists that can be applied on succeeding datasets. The potential of the software is exemplified in an experiment, in which abundance fold-changes of metabolites of the l-arginine biosynthesis in C. glutamicum type strain ATCC 13032 and l-arginine producing strain ATCC 21831 are compared. Furthermore, the capability for detection and annotation of uncommon large neutral losses is shown by the identification of (γ-)glutamyl dipeptides in the same strains. ALLocator is available online at: https://allocator.cebitec.uni-bielefeld.de. A login is required, but freely available. PMID: 25426929 [PubMed - indexed for MEDLINE]

Comparison of traditional and commercial vinegars based on metabolite profiling and antioxidant activity.

Tue, 22/12/2015 - 12:09
Related Articles Comparison of traditional and commercial vinegars based on metabolite profiling and antioxidant activity. J Microbiol Biotechnol. 2015 Feb;25(2):217-26 Authors: Jang YK, Lee MY, Kim HY, Lee S, Yeo SH, Baek SY, Lee CH Abstract Metabolite profiles of seven commercial vinegars and two traditional vinegars were performed by gas chromatography time-of-flight mass spectrometry with multivariate statistical analysis. During alcohol fermentation, yeast, nuruk, and koji were used as sugars for nutrients and as fermentation substrates. Commercial and traditional vinegars were significantly separated in the principal component analysis and orthogonal partial least square discriminant analysis. Six sugars and sugar alcohols, three organic acids, and two other components were selected as different metabolites. Target analysis by ultra-performance liquid chromatography quadruple-time-of-flight mass spectrometry and liquid chromatographyion trap-mass spectrometry/mass spectrometry were used to detect several metabolites having antioxidant activity, such as cyanidin-3-xylosylrutinoside, cyanidin-3-rutinoside, and quercetin, which were mainly detected in Rural Korean Black raspberry vinegar (RKB). These metabolites contributed to the highest antioxidant activity measured in RKB among the nine vinegars. This study revealed that MS-based metabolite profiling was useful in helping to understand the metabolite differences between commercial and traditional vinegars and to evaluate the association between active compounds of vinegar and antioxidant activity. PMID: 25293630 [PubMed - indexed for MEDLINE]

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