PubMed
Effects of bud load on quality of Beogradska besemena and Thompson seedless table grapes and cultivar differentiation based on chemometrics of analytical indices.
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Effects of bud load on quality of Beogradska besemena and Thompson seedless table grapes and cultivar differentiation based on chemometrics of analytical indices.
J Sci Food Agric. 2012 Feb;92(3):645-53
Authors: Baiano A, Terracone C
Abstract
BACKGROUND: The effects of bud load on the quality of Beogradska besemena and Thompson seedless table grape cultivars were studied. Two pruning treatments were imposed: 44 and 18 buds per vine for Beogradska besemena and 44 and 22 buds per vine for Thompson seedless.
RESULTS: In Beogradska besemena the reduction of bud load decreased titratable acidity (-4%), skin dry weight (-16%) and malic and citric acid contents (-43 and - 20%) and increased tartaric acid content (14%). The decrease in pulp antioxidant activity (-36%) was related to the decrease in hydroxycinnamoyl tartaric acid content (-13%). Concerning skin, the reduction of bud load decreased catechin and caffeoyl tartaric acid contents (-42 and - 40%) and significantly increased rutin and quercetin-3-O-glucopyranoside contents as specific compounds and flavonoids and proanthocyanidins (9 and 21%) as classes of compounds, thus causing an increase in antioxidant activity (6%). In Thompson seedless the reduction of bud load increased soluble solid content (7%), acidity (9%) and concentrations of the three organic acids (7, 3 and 14%). The increase in pulp antioxidant activity (25%) could be attributed to the increase in total phenolics (69%). The reduction of bud load caused a significant decrease in quercetin-3-O-glucopyranoside (-26%) and antioxidant activity (-15%) in skin. Principal component analysis allowed good separation between samples of the two cultivars, independently of bud level.
CONCLUSION: The results indicate that the effects of different bud loads are cultivar-dependent. Bud load and genotype differences were shown to dramatically impact the quality and antioxidant properties of table grape.
PMID: 21969062 [PubMed - indexed for MEDLINE]
The Utility of Commonly Used Laboratory Tests to Screen for Excessive Alcohol Use in Clinical Practice.
The Utility of Commonly Used Laboratory Tests to Screen for Excessive Alcohol Use in Clinical Practice.
Alcohol Clin Exp Res. 2015 Jun 25;
Authors: Gough G, Heathers L, Puckett D, Westerhold C, Ren X, Yu Z, Crabb DW, Liangpunsakul S
Abstract
BACKGROUND: This current study was undertaken to carefully assess the accuracy of routinely used laboratory tests in detecting excessive/recent alcohol use. We also determined the kinetics of these markers in subjects who underwent an intensive alcohol rehabilitation program.
METHODS: The study cohort consisted of 210 nonexcessive drinkers, 272 excessive drinkers, and 76 with alcoholic cirrhosis. To determine the kinetics of these markers during alcohol abstinence, we followed 45 subjects with history of excessive alcohol use for 12 weeks during the intensive alcohol treatment program.
RESULTS: Percentage of carbohydrate deficient transferrin (%CDT) provided the highest diagnostic performance (area under the curve [AUC] 0.77) followed by gamma-glutamyl transferase (GGT) (AUC 0.68) to detect excessive drinkers. The percentage of excessive drinkers with aspartate aminotransferase:alanine aminotransferase (AST:ALT) > 2 was only 2%, whereas 51% of subjects with alcoholic cirrhosis had AST:ALT > 2. In the multivariate analysis, the levels of GGT and %CDT were associated with the level of alcohol consumed during the past 30 days. The levels of GGT, mean corpuscular volume (MCV), and %CDT were significantly lower compared to those at baseline before alcohol rehabilitation, whereas the AST, ALT, and AST:ALT ratio were unchanged. The percent reduction was ~2.7% (for MCV), 19% (for GGT), and 43% (for %CDT) at the end of the 12-week follow-up compared to the baseline.
CONCLUSIONS: %CDT are useful markers to screen for excessive alcohol use and for follow-up of abstinence. Most subjects with excessive alcohol use do not have a high AST:ALT ratio. Rather, the AST:ALT > 2 is suggestive of alcoholic cirrhosis. The performance of the %CDT to screen for heavy alcohol use is still not ideal. Further research to identify the noninvasive marker(s) (i.e., using proteomic or metabolomics approach) should be considered.
PMID: 26110815 [PubMed - as supplied by publisher]
(1)H NMR-Based Metabolomics and Neurotoxicity Study of Cerebrum and Cerebellum in Rats Treated with Cinnabar, a Traditional Chinese Medicine.
(1)H NMR-Based Metabolomics and Neurotoxicity Study of Cerebrum and Cerebellum in Rats Treated with Cinnabar, a Traditional Chinese Medicine.
OMICS. 2015 Jun 25;
Authors: Wei L, Xue R, Zhang P, Wu Y, Li X, Pei F
Abstract
Cinnabar, an important traditional Chinese mineral medicine, has been widely used as a Chinese patent medicine ingredient for sedative therapy. Nevertheless, the neurotoxic effects of cinnabar have also been noted. In this study, (1)H NMR-based metabolomics, combined with multivariate pattern recognition, were applied to investigate the neurotoxic effects of cinnabar after intragastrical administration (dosed at 2 and 5 g/kg body weight) on male Wistar rats. The metabolite variations induced by cinnabar were characterized by increased levels of glutamate, glutamine, myo-inositol, and choline, as well as decreased levels of GABA, taurine, NAA, and NAAG in tissue extracts of the cerebellum and cerebrum. These findings suggested that cinnabar induced glutamate excitotoxicity, neuronal cell loss, osmotic state changes, membrane fluidity disruption, and oxidative injury in the brain. We also show here that there is a dose- and time-dependent neurotoxicity of cinnabar, and that cerebellum was more sensitive to cinnabar induction than cerebrum. This work illustrates the utility and reliability of (1)H NMR-based metabolomics approach for examining the potential neurotoxic effects of cinnabar and other traditional Chinese medicines.
PMID: 26110755 [PubMed - as supplied by publisher]
Metabolic Signature Profiling as a Diagnostic and Prognostic Tool in Pediatric Plasmodium falciparum Malaria.
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Metabolic Signature Profiling as a Diagnostic and Prognostic Tool in Pediatric Plasmodium falciparum Malaria.
Open Forum Infect Dis. 2015 Apr;2(2):ofv062
Authors: Surowiec I, Orikiiriza J, Karlsson E, Nelson M, Bonde M, Kyamanwa P, Karenzi B, Bergström S, Trygg J, Normark J
Abstract
Background. Accuracy in malaria diagnosis and staging is vital to reduce mortality and post infectious sequelae. In this study, we present a metabolomics approach to diagnostic staging of malaria infection, specifically Plasmodium falciparum infection in children. Methods. A group of 421 patients between 6 months and 6 years of age with mild and severe states of malaria with age-matched controls were included in the study, 107, 192, and 122, individuals, respectively. A multivariate design was used as basis for representative selection of 20 patients in each category. Patient plasma was subjected to gas chromatography-mass spectrometry analysis, and a full metabolite profile was produced from each patient. In addition, a proof-of-concept model was tested in a Plasmodium berghei in vivo model where metabolic profiles were discernible over time of infection. Results. A 2-component principal component analysis revealed that the patients could be separated into disease categories according to metabolite profiles, independently of any clinical information. Furthermore, 2 subgroups could be identified in the mild malaria cohort who we believe represent patients with divergent prognoses. Conclusions. Metabolite signature profiling could be used both for decision support in disease staging and prognostication.
PMID: 26110164 [PubMed]
Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: a review.
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Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: a review.
Metabolomics. 2015;11(4):872-894
Authors: Emwas AH, Luchinat C, Turano P, Tenori L, Roy R, Salek RM, Ryan D, Merzaban JS, Kaddurah-Daouk R, Zeri AC, Nagana Gowda GA, Raftery D, Wang Y, Brennan L, Wishart DS
Abstract
The metabolic composition of human biofluids can provide important diagnostic and prognostic information. Among the biofluids most commonly analyzed in metabolomic studies, urine appears to be particularly useful. It is abundant, readily available, easily stored and can be collected by simple, noninvasive techniques. Moreover, given its chemical complexity, urine is particularly rich in potential disease biomarkers. This makes it an ideal biofluid for detecting or monitoring disease processes. Among the metabolomic tools available for urine analysis, NMR spectroscopy has proven to be particularly well-suited, because the technique is highly reproducible and requires minimal sample handling. As it permits the identification and quantification of a wide range of compounds, independent of their chemical properties, NMR spectroscopy has been frequently used to detect or discover disease fingerprints and biomarkers in urine. Although protocols for NMR data acquisition and processing have been standardized, no consensus on protocols for urine sample selection, collection, storage and preparation in NMR-based metabolomic studies have been developed. This lack of consensus may be leading to spurious biomarkers being reported and may account for a general lack of reproducibility between laboratories. Here, we review a large number of published studies on NMR-based urine metabolic profiling with the aim of identifying key variables that may affect the results of metabolomics studies. From this survey, we identify a number of issues that require either standardization or careful accounting in experimental design and provide some recommendations for urine collection, sample preparation and data acquisition.
PMID: 26109927 [PubMed - as supplied by publisher]
A hypothetical astrocyte-microglia lactate shuttle derived from a (1)H NMR metabolomics analysis of cerebrospinal fluid from a cohort of South African children with tuberculous meningitis.
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A hypothetical astrocyte-microglia lactate shuttle derived from a (1)H NMR metabolomics analysis of cerebrospinal fluid from a cohort of South African children with tuberculous meningitis.
Metabolomics. 2015;11(4):822-837
Authors: Mason S, van Furth AM, Mienie LJ, Engelke UF, Wevers RA, Solomons R, Reinecke CJ
Abstract
Tuberculosis meningitis (TBM) is the most severe form of extra-pulmonary tuberculosis and is particularly intense in small children; there is no universally accepted algorithm for the diagnosis and substantiation of TB infection, which can lead to delayed intervention, a high risk factor for morbidity and mortality. In this study a proton magnetic resonance ((1)H NMR)-based metabolomics analysis and several chemometric methods were applied to data generated from lumber cerebrospinal fluid (CSF) samples from three experimental groups: (1) South African infants and children with confirmed TBM, (2) non-meningitis South African infants and children as controls, and (3) neurological controls from the Netherlands. A total of 16 NMR-derived CSF metabolites were identified, which clearly differentiated between the controls and TBM cases under investigation. The defining metabolites were the combination of perturbed glucose and highly elevated lactate, common to some other neurological disorders. The remaining 14 metabolites of the host's response to TBM were likewise mainly energy-associated indicators. We subsequently generated a hypothesis expressed as an "astrocyte-microglia lactate shuttle" (AMLS) based on the host's response, which emerged from the NMR-metabolomics information. Activation of microglia, as implied by the AMLS hypothesis, does not, however, present a uniform process and involves intricate interactions and feedback loops between the microglia, astrocytes and neurons that hamper attempts to construct basic and linear cascades of cause and effect; TBM involves a complex integration of the responses from the various cell types present within the CNS, with microglia and the astrocytes as main players.
PMID: 26109926 [PubMed - as supplied by publisher]
Can we trust untargeted metabolomics? Results of the metabo-ring initiative, a large-scale, multi-instrument inter-laboratory study.
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Can we trust untargeted metabolomics? Results of the metabo-ring initiative, a large-scale, multi-instrument inter-laboratory study.
Metabolomics. 2015;11(4):807-821
Authors: Martin JC, Maillot M, Mazerolles G, Verdu A, Lyan B, Migné C, Defoort C, Canlet C, Junot C, Guillou C, Manach C, Jabob D, Bouveresse DJ, Paris E, Pujos-Guillot E, Jourdan F, Giacomoni F, Courant F, Favé G, Le Gall G, Chassaigne H, Tabet JC, Martin JF, Antignac JP, Shintu L, Defernez M, Philo M, Alexandre-Gouaubau MC, Amiot-Carlin MJ, Bossis M, Triba MN, Stojilkovic N, Banzet N, Molinié R, Bott R, Goulitquer S, Caldarelli S, Rutledge DN
Abstract
The metabo-ring initiative brought together five nuclear magnetic resonance instruments (NMR) and 11 different mass spectrometers with the objective of assessing the reliability of untargeted metabolomics approaches in obtaining comparable metabolomics profiles. This was estimated by measuring the proportion of common spectral information extracted from the different LCMS and NMR platforms. Biological samples obtained from 2 different conditions were analysed by the partners using their own in-house protocols. Test #1 examined urine samples from adult volunteers either spiked or not spiked with 32 metabolite standards. Test #2 involved a low biological contrast situation comparing the plasma of rats fed a diet either supplemented or not with vitamin D. The spectral information from each instrument was assembled into separate statistical blocks. Correlations between blocks (e.g., instruments) were examined (RV coefficients) along with the structure of the common spectral information (common components and specific weights analysis). In addition, in Test #1, an outlier individual was blindly introduced, and its identification by the various platforms was evaluated. Despite large differences in the number of spectral features produced after post-processing and the heterogeneity of the analytical conditions and the data treatment, the spectral information both within (NMR and LCMS) and across methods (NMR vs. LCMS) was highly convergent (from 64 to 91 % on average). No effect of the LCMS instrumentation (TOF, QTOF, LTQ-Orbitrap) was noted. The outlier individual was best detected and characterised by LCMS instruments. In conclusion, untargeted metabolomics analyses report consistent information within and across instruments of various technologies, even without prior standardisation.
PMID: 26109925 [PubMed - as supplied by publisher]
Training needs in metabolomics.
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Training needs in metabolomics.
Metabolomics. 2015;11(4):784-786
Authors: Weber RJ, Winder CL, Larcombe LD, Dunn WB, Viant MR
PMID: 26109924 [PubMed - as supplied by publisher]
Histone Deacetylase 4 promotes cholestatic liver injury in the absence of Prohibitin-1.
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Histone Deacetylase 4 promotes cholestatic liver injury in the absence of Prohibitin-1.
Hepatology. 2015 Jun 25;
Authors: Barbier-Torres L, Beraza N, Fernández-Tussy P, Lopitz-Otsoa F, Fernández-Ramos D, Zubiete-Franco I, Varela-Rey M, Delgado TC, Gutiérrez V, Anguita J, Pares A, Banales JM, Villa E, Caballería J, Alvarez L, Lu SC, Mato JM, Martínez-Chantar ML
Abstract
Prohibitin 1 (PHB1) is an evolutionary conserved pleiotropic protein that participates in diverse processes depending on its subcellular localization and interactome. Recent data have indicated a diverse role for PHB1 in the pathogenesis of obesity, cancer and inflammatory bowel disease, among others. Data presented here suggest that PHB1 is also linked to cholestatic liver disease. PHB1 expression is markedly reduced in patients with primary billiary cirrhosis and biliary atresia and Alagille syndrome, two major pediatric cholestatic conditions. In the experimental model of bile duct ligation, silencing of PHB1 induced liver fibrosis, reduced animal survival and induced bile duct proliferation. Importantly, the modulatory effect of PHB1 is not dependent on its known mitochondrial function. Importantly,d PHB1 interacts with Histone Deacetylase 4 (HDAC4) in the presence of bile acids. Hence, PHB1 depletion leads to increased nuclear HDAC4 content and its associated epigenetic changes. Remarkably, HDAC4 silencing and the administration of the HDAC inhibitor parthenolide during obstructive cholestasis in vivo promote genomic reprogramming leading to the regression of the fibrotic phenotype in the liver-specific Phb1 KO mice.
CONCLUSION: Our data identify PHB1 as an important mediator of cholestatic liver injury regulating the activity of HDAC4, which controls specific epigenetic marks. These results identify potential novel strategies to treat liver injury and fibrosis, particularly as a consequence of chronic cholestasis. This article is protected by copyright. All rights reserved.
PMID: 26109312 [PubMed - as supplied by publisher]
HRMAS NMR Analysis of Algae and Identification of Molecules of Interest via Conventional 1D and 2D NMR: Sample Preparation and Optimization of Experimental Conditions.
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HRMAS NMR Analysis of Algae and Identification of Molecules of Interest via Conventional 1D and 2D NMR: Sample Preparation and Optimization of Experimental Conditions.
Methods Mol Biol. 2015;1308:191-205
Authors: Simon G, Kervarec N, Cérantola S
Abstract
Nuclear magnetic resonance (NMR) has become an astounding tool for molecular characterization. Thanks to the development of probes and the increase of magnetic field, NMR has entered the field of biology and facilitated the identification of natural compounds. Indeed, this nondestructive NMR tool makes possible the complete characterization of less and less quantities of material via 1D and 2D sequences on many nuclei (e.g., (1)H, (13)C, (31)P, (15)N). More recently, the development of high-resolution magic-angle spinning (HRMAS) probes have permitted direct analysis of living tissue (e.g., a piece of algae) without prior extraction providing information on both the total content and the ratio of different molecules within the sample; thus HRMAS facilitates a wide range of analyses, such as species differentiation or studies of metabolomics according to various environmental or experimental conditions. This chapter describes the specific sample preparation, based on an algal sample or extract, required for all NMR analyses in order to optimize the NMR response and obtain the most valuable information.
PMID: 26108507 [PubMed - in process]
Marine Algae: a Source of Biomass for Biotechnological Applications.
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Marine Algae: a Source of Biomass for Biotechnological Applications.
Methods Mol Biol. 2015;1308:1-37
Authors: Stengel DB, Connan S
Abstract
Biomass derived from marine microalgae and macroalgae is globally recognized as a source of valuable chemical constituents with applications in the agri-horticultural sector (including animal feeds and health and plant stimulants), as human food and food ingredients as well as in the nutraceutical, cosmeceutical, and pharmaceutical industries. Algal biomass supply of sufficient quality and quantity however remains a concern with increasing environmental pressures conflicting with the growing demand. Recent attempts in supplying consistent, safe and environmentally acceptable biomass through cultivation of (macro- and micro-) algal biomass have concentrated on characterizing natural variability in bioactives, and optimizing cultivated materials through strain selection and hybridization, as well as breeding and, more recently, genetic improvements of biomass. Biotechnological tools including metabolomics, transcriptomics, and genomics have recently been extended to algae but, in comparison to microbial or plant biomass, still remain underdeveloped. Current progress in algal biotechnology is driven by an increased demand for new sources of biomass due to several global challenges, new discoveries and technologies available as well as an increased global awareness of the many applications of algae. Algal diversity and complexity provides significant potential provided that shortages in suitable and safe biomass can be met, and consumer demands are matched by commercial investment in product development.
PMID: 26108496 [PubMed - in process]
Interaction and signalling between a cosmopolitan phytoplankton and associated bacteria.
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Interaction and signalling between a cosmopolitan phytoplankton and associated bacteria.
Nature. 2015 Jun 4;522(7554):98-101
Authors: Amin SA, Hmelo LR, van Tol HM, Durham BP, Carlson LT, Heal KR, Morales RL, Berthiaume CT, Parker MS, Djunaedi B, Ingalls AE, Parsek MR, Moran MA, Armbrust EV
Abstract
Interactions between primary producers and bacteria impact the physiology of both partners, alter the chemistry of their environment, and shape ecosystem diversity. In marine ecosystems, these interactions are difficult to study partly because the major photosynthetic organisms are microscopic, unicellular phytoplankton. Coastal phytoplankton communities are dominated by diatoms, which generate approximately 40% of marine primary production and form the base of many marine food webs. Diatoms co-occur with specific bacterial taxa, but the mechanisms of potential interactions are mostly unknown. Here we tease apart a bacterial consortium associated with a globally distributed diatom and find that a Sulfitobacter species promotes diatom cell division via secretion of the hormone indole-3-acetic acid, synthesized by the bacterium using both diatom-secreted and endogenous tryptophan. Indole-3-acetic acid and tryptophan serve as signalling molecules that are part of a complex exchange of nutrients, including diatom-excreted organosulfur molecules and bacterial-excreted ammonia. The potential prevalence of this mode of signalling in the oceans is corroborated by metabolite and metatranscriptome analyses that show widespread indole-3-acetic acid production by Sulfitobacter-related bacteria, particularly in coastal environments. Our study expands on the emerging recognition that marine microbial communities are part of tightly connected networks by providing evidence that these interactions are mediated through production and exchange of infochemicals.
PMID: 26017307 [PubMed - indexed for MEDLINE]
GATA4 is a key regulator of steroidogenesis and glycolysis in mouse Leydig cells.
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GATA4 is a key regulator of steroidogenesis and glycolysis in mouse Leydig cells.
Endocrinology. 2015 May;156(5):1860-72
Authors: Schrade A, Kyrönlahti A, Akinrinade O, Pihlajoki M, Häkkinen M, Fischer S, Alastalo TP, Velagapudi V, Toppari J, Wilson DB, Heikinheimo M
Abstract
Transcription factor GATA4 is expressed in somatic cells of the mammalian testis. Gene targeting studies in mice have shown that GATA4 is essential for proper differentiation and function of Sertoli cells. The role of GATA4 in Leydig cell development, however, remains controversial, because targeted mutagenesis experiments in mice have not shown a consistent phenotype, possibly due to context-dependent effects or compensatory responses. We therefore undertook a reductionist approach to study the function of GATA4 in Leydig cells. Using microarray analysis and quantitative RT-PCR, we identified a set of genes that are down-regulated or up-regulated after small interfering RNA (siRNA)-mediated silencing of Gata4 in the murine Leydig tumor cell line mLTC-1. These same genes were dysregulated when primary cultures of Gata4(flox/flox) adult Leydig cells were subjected to adenovirus-mediated cre-lox recombination in vitro. Among the down-regulated genes were enzymes of the androgen biosynthetic pathway (Cyp11a1, Hsd3b1, Cyp17a1, and Srd5a). Silencing of Gata4 expression in mLTC-1 cells was accompanied by reduced production of sex steroid precursors, as documented by mass spectrometric analysis. Comprehensive metabolomic analysis of GATA4-deficient mLTC-1 cells showed alteration of other metabolic pathways, notably glycolysis. GATA4-depleted mLTC-1 cells had reduced expression of glycolytic genes (Hk1, Gpi1, Pfkp, and Pgam1), lower intracellular levels of ATP, and increased extracellular levels of glucose. Our findings suggest that GATA4 plays a pivotal role in Leydig cell function and provide novel insights into metabolic regulation in this cell type.
PMID: 25668067 [PubMed - indexed for MEDLINE]
Clinical severity of visceral leishmaniasis is associated with changes in immunoglobulin g fc N-glycosylation.
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Clinical severity of visceral leishmaniasis is associated with changes in immunoglobulin g fc N-glycosylation.
MBio. 2014;5(6):e01844
Authors: Gardinassi LG, Dotz V, Hipgrave Ederveen A, de Almeida RP, Nery Costa CH, Costa DL, de Jesus AR, Mayboroda OA, Garcia GR, Wuhrer M, de Miranda Santos IK
Abstract
UNLABELLED: Visceral leishmaniasis (VL) has a high fatality rate if not treated; nevertheless, the majority of human infections with the causative agent, Leishmania infantum chagasi, are asymptomatic. Although VL patients often present with increased levels of serum immunoglobulins, the contribution of antibodies to resistance or progression to disease remains unknown. Effector and regulatory functions of antibodies rely on their interactions with type I and II Fc receptors, and these interactions are tuned by the patterns of antibody Fc N-glycosylation. In view of these facts, we applied a robust method of IgG Fc N-glycopeptide profiling of serum samples from 187 patients with VL, 177 asymptomatic individuals, 116 endemic controls (individuals residing in areas where VL is endemic) and 43 nonendemic controls (individuals living in an area where VL is not endemic). We show that, in comparison to the overall IgG Fc N-glycan profiles of asymptomatic or uninfected healthy individuals, those of patients with VL are profoundly altered. These changes correlate with levels of serum cytokines and the inflammation marker C-reactive protein. We also fitted univariate and multivariate ordinal logistic regression models to demonstrate the ability of IgG Fc N-glycosylation features and immunity regulators present in serum to predict disease severity in VL patients. Importantly, we show that Fc N-glycosylation profiles change after treatment of VL. This study introduces important concepts contributing to the understanding of antibody responses in infections with Leishmania parasites and provides new insights into the pathology of human VL.
IMPORTANCE: Immunoglobulins (Ig) have been shown to present pro- and anti-inflammatory functions according to the profile of carbohydrates attached to their Fc region. Glycosylation features of serum IgG have been examined in relation to several autoimmune and infectious diseases and provide a mechanistic basis for the protective or pathogenic role of antibodies. Leishmania infantum chagasi is the causative agent of visceral leishmaniasis (VL) in South America, and we show that VL patients produce IgG with patterns of Fc glycans similar to those found in other inflammatory conditions. Specific Fc N-glycosylation features and levels of serum cytokines and C-reactive protein are significantly associated with the development of severe clinical symptoms and, notably, Fc glycosylation changes after treatment. The modifications detected in the N-glycosylation features of IgG Fc from VL patients raise new perspectives on the effector or regulatory role of antibodies in immune responses elicited by infection with Leishmania parasites.
PMID: 25467439 [PubMed - indexed for MEDLINE]
A metabolomic study of preterm and term human and formula milk by proton MRS analysis: preliminary results.
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A metabolomic study of preterm and term human and formula milk by proton MRS analysis: preliminary results.
J Matern Fetal Neonatal Med. 2014 Oct;27 Suppl 2:27-33
Authors: Longini M, Tataranno ML, Proietti F, Tortoriello M, Belvisi E, Vivi A, Tassini M, Perrone S, Buonocore G
Abstract
OBJECTIVE: To investigate changes in global metabolic profile between: 1 - breast milk and formula milk, 2 - breast milk from mothers delivering at different gestational age (GA) collected within one week from delivery, and then week by week until term equivalent age.
METHODS: Proton magnetic resonance spectroscopy (MRS) was used to analyze the water-soluble and lipid fractions extracted from 50 milk samples, 46 human milk at different GA, from 23 weeks of gestation until term equivalent age and four different formula milks.
RESULTS: The formula milk for premature infants was the most similar to breast milk of preterm babies. Breast milk showed higher lactose concentrations than formula milk, that conversely presented higher galactose 1-phosphate and maltose concentrations. Mother's milk of very preterm babies (23-25 wks of GA) showed a different metabolic profile from preterm infants ≥29 wks of GA with a subsequent trend to similarity around the 30th week of post-natal age. Breast milk from preterm infants of 29-34 wks, collected up to 40 wks of post-natal age showed a temporal change over the first three weeks of lactation, approaching to zero with the achievement of term age.
CONCLUSIONS: Metabolome is a promising tool to study human and artificial milk global metabolic profile.
PMID: 25284174 [PubMed - indexed for MEDLINE]
Neonatomics and childomics: the right route to the future.
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Neonatomics and childomics: the right route to the future.
J Matern Fetal Neonatal Med. 2014 Oct;27 Suppl 2:1-3
Authors: Fanos V, Buonocore G, Mussap M
PMID: 25284170 [PubMed - indexed for MEDLINE]
Metabolomics Analysis Reveals that AICAR Affects Glycerolipid, Ceramide and Nucleotide Synthesis Pathways in INS-1 Cells.
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Metabolomics Analysis Reveals that AICAR Affects Glycerolipid, Ceramide and Nucleotide Synthesis Pathways in INS-1 Cells.
PLoS One. 2015;10(6):e0129029
Authors: ElAzzouny MA, Evans CR, Burant CF, Kennedy RT
Abstract
AMPK regulates many metabolic pathways including fatty acid and glucose metabolism, both of which are closely associated with insulin secretion in pancreatic β-cells. Insulin secretion is regulated by metabolic coupling factors such as ATP/ADP ratio and other metabolites generated by the metabolism of nutrients such as glucose, fatty acid and amino acids. However, the connection between AMPK activation and insulin secretion in β-cells has not yet been fully elucidated at a metabolic level. To study the effect of AMPK activation on glucose stimulated insulin secretion, we applied the pharmacological activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) to an INS-1 (832/13) β-cell line. We measured the change in 66 metabolites in the presence or absence of AICAR using different stable isotopic labeled nutrients to probe selected pathways. AMPK activation by AICAR increased basal insulin secretion and reduced the glucose stimulation index. Although ATP/ADP ratios were not strongly affected by AICAR, several other metabolites and pathways important for insulin secretion were affected by AICAR treatment including long-chain CoAs, malonyl-CoA, 3-hydroxy-3 methylglutaryl CoA, diacylglycerol, and farnesyl pyrophosphate. Tracer studies using 13C-glucose revealed lower glucose flux in the purine and pyrimidine pathway and in the glycerolipid synthesis pathway. Untargeted metabolomics revealed reduction in ceramides caused by AICAR that may explain the beneficial role of AMPK in protecting β-cells from lipotoxicity. Taken together, the results provide an overall picture of the metabolic changes associated with AICAR treatment and how it modulates insulin secretion and β-cell survival.
PMID: 26107620 [PubMed - as supplied by publisher]
The ACTN3 R577X Polymorphism Is Associated with Cardiometabolic Fitness in Healthy Young Adults.
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The ACTN3 R577X Polymorphism Is Associated with Cardiometabolic Fitness in Healthy Young Adults.
PLoS One. 2015;10(6):e0130644
Authors: Deschamps CL, Connors KE, Klein MS, Johnsen VL, Shearer J, Vogel HJ, Devaney JM, Gordish-Dressman H, Many GM, Barfield W, Hoffman EP, Kraus WE, Hittel DS
Abstract
Homozygosity for a premature stop codon (X) in the ACTN3 "sprinter" gene is common in humans despite the fact that it reduces muscle size, strength and power. Because of the close relationship between skeletal muscle function and cardiometabolic health we examined the influence of ACTN3 R577X polymorphism over cardiovascular and metabolic characteristics of young adults (n = 98 males, n = 102 females; 23 ± 4.2 years) from our Assessing Inherent Markers for Metabolic syndrome in the Young (AIMMY) study. Both males and females with the RR vs XX genotype achieved higher mean VO2 peak scores (47.8 ± 1.5 vs 43.2 ±1.8 ml/O2/min, p = 0.002) and exhibited higher resting systolic (115 ± 2 vs 105 ± mmHg, p = 0.027) and diastolic (69 ± 3 vs 59 ± 3 mmHg, p = 0.005) blood pressure suggesting a role for ACTN3 in the maintenance of vascular tone. We subsequently identified the expression of alpha-actinin 3 protein in pulmonary artery smooth muscle, which may explain the genotype-specific differences in cardiovascular adaptation to acute exercise. In addition, we utilized targeted serum metabolomics to distinguish between RR and XX genotypes, suggesting an additional role for the ACTN3 R577X polymorphism in human metabolism. Taken together, these results identify significant cardiometabolic effects associated with possessing one or more functional copies of the ACTN3 gene.
PMID: 26107372 [PubMed - as supplied by publisher]
Homolog-focused profiling of ginsenosides based on the integration of step-wise formate anion-to-deprotonated ion transition screening and scheduled multiple reaction monitoring.
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Homolog-focused profiling of ginsenosides based on the integration of step-wise formate anion-to-deprotonated ion transition screening and scheduled multiple reaction monitoring.
J Chromatogr A. 2015 Jun 12;
Authors: Song Y, Zhang N, Shi S, Li J, Zhao Y, Zhang Q, Jiang Y, Tu P
Abstract
Homolog-focused profiling is a favored option to bridge targeted metabolomics toward non-targeted metabolomics. In current study, an attempt was made for the large-scale ginsenoside-specific analysis in ginseng (G) and American ginseng (AG). When formic acid (0.1%, v/v) was introduced as the mobile phase additive, formate anion-to-deprotonated ion transitions ([M+HCOO](-)>[M-H](-)) with an optimal collision energy (-32eV) could result in satisfactory responses for ginsenosides. Therefore, a step-wise multiple reaction monitoring (MRM)-based method employing [M+HCOO](-)>[M-H](-) ion pairs was constructed to screen ginsenosides among 501-1250u (for Q1) with a step-size of 2u, and MRM also served as a survey experiment to trigger enhanced product ion scans for MS(2) spectrum acquisition on a hybrid triple quadrupole-linear ion trap mass spectrometer; then, the identification of those observed ginsenosides was achieved on the basis of the well-defined mass cracking patterns for ginsenosides; afterwards, scheduled MRM was introduced for large-scale relatively quantitative analysis of all detected ginsenosides. Finally, comparative metabolomics were performed to differentiate G, AG, and their processed products. Method validation was carried out using thirteen authentic compounds. A total of 221 ginsenosides, among which 185 ones were annotated, were observed and relatively quantitated. All crude materials were obviously classified into groups I-III. Above all, the MRM-based homolog-focused profiling of ginsenosides could be used as a reliable tool to gain an in-depth view for ginsenoside-enriched herbal products.
PMID: 26105782 [PubMed - as supplied by publisher]
Metabolomics of Central Carbon Metabolism in Mycobacterium tuberculosis.
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Metabolomics of Central Carbon Metabolism in Mycobacterium tuberculosis.
Microbiol Spectr. 2014 Jun;2(3)
Authors: Baughn AD, Rhee KY
Abstract
Metabolism is a biochemical activity of all cells, thought to fuel the physiologic needs of a given cell in a quantitative, rather than qualitatively specific, manner. Mycobacterium tuberculosis is a chronic facultative intracellular pathogen that resides in humans as its only known host and reservoir. Within humans, M. tuberculosis resides chiefly in the macrophage phagosome, the cell type and compartment most committed to its eradication. M. tuberculosis thus occupies the majority of its decades-long life cycle in a state of slowed or arrested replication. At the same time, M. tuberculosis remains poised to reenter the cell cycle to ensure its propagation as a species. M. tuberculosis has thus evolved its metabolic network to both maintain and propagate its survival as a species within a single host. Knowledge of the specific ways in which its metabolic network serves these distinct though interdependent functions, however, remains highly incomplete. In this article we review existing knowledge of M. tuberculosis's central carbon metabolism as reported by studies of its basic genetic and biochemical composition, regulation, and organization, with the hope that such knowledge will inform our understanding of M. tuberculosis's ability to traverse the stringent and heterogeneous niches encountered in the host.
PMID: 26103978 [PubMed - in process]