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

Data on the changes of the mussels׳ metabolic profile under different cold storage conditions.

Sat, 16/04/2016 - 12:33
Data on the changes of the mussels׳ metabolic profile under different cold storage conditions. Data Brief. 2016 Jun;7:951-7 Authors: Aru V, Pisano MB, Savorani F, Engelsen SB, Cosentino S, Cesare Marincola F Abstract One of the main problems of seafood marketing is the ease with which fish and shellfish undergo deterioration after death. (1)H NMR spectroscopy and microbiological analysis were applied to get in depth insight into the effects of cold storage (4 °C and 0 °C) on the spoilage of the mussel Mytilus galloprovincialis. This data article provides information on the average distribution of the microbial loads in mussels׳ specimens and on the acquisition, processing, and multivariate analysis of the (1)H NMR spectra from the hydrosoluble phase of stored mussels. This data article is referred to the research article entitled "Metabolomics analysis of shucked mussels' freshness" (Aru et al., 2016) [1]. PMID: 27081673 [PubMed]

Microbial biotransformation of polyphenols during in vitro colonic fermentation of masticated mango and banana.

Sat, 16/04/2016 - 12:33
Microbial biotransformation of polyphenols during in vitro colonic fermentation of masticated mango and banana. Food Chem. 2016 Sep 15;207:214-22 Authors: Low DY, Hodson MP, Williams BA, D'Arcy BR, Gidley MJ Abstract Mango and banana cell structures, which survived in vivo mastication and in vitro gastrointestinal digestion, were fermented in vitro for 48h. For both fruits, flavonoids and phenolic acids were liberated and underwent microbial metabolism involving ring fission, dehydroxylation and decarboxylation. UHPLC-PDA/Q-ToF-MS profiles revealed rapid degradation (72-78%) of most intact precursors (epicatechin and several unidentified compounds) within 10h, before the exponential phase of the cumulative gas production. Concomitant formation of catabolites (e.g. 4-hydroxyphenylacetic acid) occurred within 4-8h, while metabolism of catechin derivative and 3-(4-hydroxyphenyl)propanoic acid continued slowly for at least 48h, suggesting intact plant cell walls can be a controlling factor in microbial susceptibility. Untargeted PCA and OPLS-DA demonstrated clear classifications in the compositional fruit type and compound profiles as a function of time. Clusters and distinct discriminating compounds were recognised, which could lead to subsequent biomarker identification for establishing differences in polyphenol microbial metabolism of various fruit matrices. PMID: 27080899 [PubMed - in process]

Methods used to increase the comprehensive coverage of urinary and plasma metabolomes by MS.

Sat, 16/04/2016 - 12:33
Methods used to increase the comprehensive coverage of urinary and plasma metabolomes by MS. Bioanalysis. 2016 Apr 15; Authors: Chen Y, Xu J, Zhang R, Abliz Z Abstract Metabolomics, focusing on comprehensive analysis of all the metabolites in a biological system, provides a direct signature of biochemical activity. Using emerging technologies in MS, it is possible to simultaneously and rapidly analyze thousands of metabolites. However, due to the chemical and physical diversity of metabolites, it is difficult to acquire a comprehensive and reliable profiling of the whole metabolome. Here, we summarize the state of the art in metabolomics research, focusing on efforts to provide a more comprehensive metabolome coverage via improvements in two fundamental processes: sample preparation and MS analysis. Additionally, the reliable analysis is also highlighted via the combinations of multiple methods (e.g., targeted and untargeted approaches), and analytical quality control and calibration methods. PMID: 27079429 [PubMed - as supplied by publisher]

metabolomics; +20 new citations

Fri, 15/04/2016 - 12:01
20 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 2016/04/15PubMed comprises more than 24 million 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; +32 new citations

Thu, 14/04/2016 - 13:57
32 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 2016/04/14PubMed comprises more than 24 million 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; +26 new citations

Tue, 12/04/2016 - 12:39
26 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 2016/04/12PubMed comprises more than 24 million 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.

Effects and mechanisms of Shaofu-Zhuyu decoction and its major bioactive component for Cold - Stagnation and Blood - Stasis primary dysmenorrhea rats.

Mon, 11/04/2016 - 18:14
Effects and mechanisms of Shaofu-Zhuyu decoction and its major bioactive component for Cold - Stagnation and Blood - Stasis primary dysmenorrhea rats. J Ethnopharmacol. 2016 Apr 6; Authors: Huang X, Su S, Duan JA, Sha X, Zhu KY, Guo J, Yu L, Liu P, Shang E, Qian D Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) is used under the guidance of the theory of traditional Chinese medical sciences in clinical application. The Chinese herbal formula, Shaofu Zhuyu decoction (SFZYD), is considered as an effective prescription for treating Cold - Stagnation and Blood - Stasis (CSBS) primary dysmenorrhea. The previous studies showed the SFZYD exhibited great anti-inflammation and analgesic effect. In this present study the metabolomics of CSBS primary dysmenorrhea diseased rats and the cytokine transcription in PHA stimulated-PBMC were investigated to explore the effects and mechanisms. AIM OF THE STUDY: Explore a valuable insight into the effects and mechanisms of SFZYD for Cold - Stagnation and Blood - Stasis primary dysmenorrhea rats. MATERIALS AND METHODS: We established CSBS primary dysmenorrhea diseased rats according the clinical symptoms. A targeted tandem mass spectrometry (MS/MS)-based metabolomic platform was used to evaluate the metabolic profiling changes and the intervention by SFZYD. The PBMC cell was adopted to explore the mechanisms by analyzing the signaling pathway evaluated by expression of inflammatory cytokines, c-jun and c-fos and corresponding phosphorylation levels. RESULTS: Estradiol, oxytocin, progesterone, endothelin, β-endorphin and PGF2α were restored back to the normal level after the treatment of SFZYD. Total twenty-five metabolites (ten in plasma and fifteen in urine), up-regulated or down-regulated, were identified. These identified biomarkers underpinning the metabolic pathway including pentose and glucuronate interconversions, steroid hormone biosynthesis, and glycerophospholipid metabolism are disturbed in model rats. Among these metabolites, twenty one potential biomarkers were regulated after SFZYD treated. The compound of paeoniflorin, a major bioactive compound in SFZYD, was proved to regulate the MAPK signaling pathway by inhibiting the expression of IL-1β, IL-2, IL-10, IL-12, TNFα, INFγ, C-jun and C-fos in PHA stimulated-PBMC. CONCLUSION: These findings indicated that SFZYD improved the metabolic profiling and biochemical indicators on CSBS primary dysmenorrhea rats. And the mechanisms were closely related with the regulation of the MAPK pathway by reduction in phosphorylated forms of the three MAPK (ERK1/2, p38 and JNK) and down regulation of c-jun and c-fos by paeoniflorin. The data could be provided the guidance for further research and new drug discovery. PMID: 27060631 [PubMed - as supplied by publisher]

Isolation and characterization of a mutant defective in triacylglycerol accumulation in nitrogen-starved Chlamydomonas reinhardtii.

Mon, 11/04/2016 - 18:14
Isolation and characterization of a mutant defective in triacylglycerol accumulation in nitrogen-starved Chlamydomonas reinhardtii. Biochim Biophys Acta. 2016 Apr 6; Authors: Hung CH, Kanehara K, Nakamura Y Abstract Triacylglycerol (TAG), a major source of biodiesel production, accumulates in nitrogen-starved Chlamydomonas reinhardtii. However, the metabolic pathway of starch-to-TAG conversion remains elusive because an enzyme that affects the starch degradation is unknown. Here, we isolated a new class of mutant bgal1, which expressed an overaccumulation of starch granules and defective photosynthetic growth. The bgal1 was a null mutant of a previously uncharacterized β-galactosidase-like gene (Cre02.g119700), which decreased total β-galactosidase activity 40% of wild type. Upon nitrogen starvation, the bgal1 mutant showed decreased TAG accumulation mainly due to the reduced flux of de novo TAG biosynthesis evidenced by increased unsaturation of fatty acid composition in TAG and reduced TAG accumulation by additional supplementation of acetate to the culture media. Metabolomic analysis of the bgal1 mutant showed significantly reduced levels of metabolites following the hydrolysis of starch and substrates for TAG accumulation, whereas metabolites in TCA cycle were unaffected. Upon nitrogen starvation, while levels of glucose 6-phosphate, fluctose 6-phosphate and acetyl-CoA remained lower, most of the other metabolites in glycolysis were increased but those in the TCA cycle were decreased, supporting TAG accumulation. We suggest that BGAL1 may be involved in the degradation of starch, which affects TAG accumulation in nitrogen-starved C. reinhardtii. PMID: 27060488 [PubMed - as supplied by publisher]

Dietary vitamin A supplementation ameliorates the effects of poly-aromatic hydrocarbons in Atlantic salmon (Salmo salar).

Mon, 11/04/2016 - 18:14
Dietary vitamin A supplementation ameliorates the effects of poly-aromatic hydrocarbons in Atlantic salmon (Salmo salar). Aquat Toxicol. 2016 Mar 21;175:171-183 Authors: Berntssen MH, Ørnsrud R, Rasinger J, Søfteland L, Lock EJ, Kolås K, Moren M, Hylland K, Silva J, Johansen J, Lie K Abstract Several studies have reported on the interaction between vitamin A (VA) and aryl hydrocarbon receptor (AhR)-binding toxicants, including poly-aromatic hydrocarbons (PAHs). In aquaculture, the use of plant oils in novel aquafeeds can increase PAH levels while simultaneously lowering natural VA background levels, causing the need to supplement plant oil-based feeds with synthetic VA. To study dietary VA-PAH interactions, Atlantic salmon (initial weight 195±0.15g) were fed four identical plant-based diets that were supplemented with PAHs (100 and 10mgkg(-1) benzo[a]pyrene (BaP) and phenanthrene (Phe), respectively) or VA (retinyl acetate 8721IUkg(-1)) separately or combined for 2.5 months in a 2×2 factorial design, with triplicate net-pens per diet. Dietary PAH significantly reduced hepatic VA storage, and VA-enriched diets restored hepatic VA. There was a significant PAH-VA interaction effect on hepatic BaP, but not Phe, accumulation, with reduced hepatic BaP concentrations in fish fed VA+PAH compared to fish fed PAH alone. Concurrently, PAH and VA significantly interacted in their effects on CYP1A phase I biotransformation as observed from increased ethoxyresorufin-O-deethylase (EROD) activity, increased CYP1A protein concentration, and elevated transcription (cyp1a1 gene expression) in fish fed PAH+VA compared to PAH alone. Dietary VA supplementation alone had no significant effect on CYP1A phase I biotransformation. Metabolomic assessment showed that dietary VA caused a restoration of metabolic intermediates involved in energy metabolism that were affected by dietary PAH. Moreover, a PAH-induced growth inhibition was partially ameliorated by dietary VA supplementation. In conclusion, dietary VA interacted with PAH toxicity on the level of CYP1A-mediated detoxification, hepatic PAH accumulation, energy allocation, and growth. PMID: 27060237 [PubMed - as supplied by publisher]

Repeated implantation failure versus repeated implantation success: discrimination at a metabolomic level.

Mon, 11/04/2016 - 18:14
Repeated implantation failure versus repeated implantation success: discrimination at a metabolomic level. Hum Reprod. 2016 Apr 8; Authors: RoyChoudhury S, Singh A, Gupta NJ, Srivastava S, Joshi MV, Chakravarty B, Chaudhury K Abstract STUDY QUESTION: Is there any difference at the serum metabolic level between women with recurrent implantation failure (RIF) and women with recurrent implantation success (RIS) when undergoing in vitro fertilization (IVF)? SUMMARY ANSWER: Eight metabolites, including valine, adipic acid, l-lysine, creatine, ornithine, glycerol, d-glucose and urea, were found to be significantly up-regulated in women with RIF when compared with women with RIS. WHAT IS KNOWN ALREADY: Despite transfer of three high-grade embryos per cycle, RIF following three or more consecutive IVF attempts occurs in a group of infertile women. Conversely, there is a group of women who undergo successful implantation each cycle, yet have a poor obstetric history. STUDY DESIGN, SIZE, DURATION: This study was conducted over a period of 10 years (January 2004-October 2014). Groups of 28 women with RIF (age ≤40 years and BMI ≤28) and 24 women with RIS (age and BMI matched) were selected from couples with primary infertility reporting at the Institute of Reproductive Medicine, Kolkata, India. Women recruited in the RIF group had history of implantation failure in at least three consecutive IVF attempts, in which three embryos of high-grade quality were transferred in each cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: Blood samples were collected from both the groups during the implantation window following overnight fasting for at least 10 h (7-10 days post ovulation). Samples were analyzed using a 700 MHz NMR spectrometer and acquired spectra were subjected to chemometric and statistical analysis. Serum levels of endothelial nitric oxide synthase (eNOS) were measured using an enzyme immunoassay technique. MAIN RESULTS AND THE ROLE OF CHANCE: Valine, adipic acid, l-lysine, creatine, ornithine, glycerol, d-glucose and urea were found to be significantly down-regulated in women with RIS when compared with those with RIF, with fold change values of 0.81, 0.82, 0.79, 0.80, 0.78, 0.68, 0.76 and 0.74, respectively. Further, serum eNOS was found to be significantly lower in women with RIF when compared with RIS (P < 0.05), indicating possible impairment in nitric oxide production. Metabolites, mostly related to energy metabolism, lipid metabolism and the arginine metabolic pathway were found to be considerably altered and are likely to be associated with the RIF phenomenon. However, the interplay between these molecules in RIF is complex and holds merit for further exploration. LIMITATIONS, REASONS FOR CAUTION: In-depth studies of the arginine metabolic pathway in endometrial tissues seem necessary to validate our findings. A limitation of the present study is that the metabolic level changes, eNOS and nitric oxide levels have not been investigated in the endometrial tissues of the two groups of women. It would be interesting to investigate whether there exists a direct link between metabolic dysregulation and genetic factors that affects implantation in RIF women. WIDER IMPLICATIONS OF THE FINDINGS: We speculate that tissue metabolomics can provide an improved understanding of the metabolic dysfunction associated with RIF. The identification of serum metabolic marker(s) in women with RIS may help with strategies of early therapeutic intervention, which may improve the chances of implantation significantly in women otherwise susceptible to IVF failure. STUDY FUNDING/COMPETING INTERESTS: One of the authors, S.R.C. acknowledges the Council of Scientific and Industrial Research (CSIR), Government of India [No: 9/81(1228)/14, EMR-I] for financial support. PMID: 27060172 [PubMed - as supplied by publisher]

Metabolic responses of clams, Ruditapes decussatus and Ruditapes philippinarum, to short-term exposure to lead and zinc.

Mon, 11/04/2016 - 18:14
Metabolic responses of clams, Ruditapes decussatus and Ruditapes philippinarum, to short-term exposure to lead and zinc. Mar Pollut Bull. 2016 Apr 5; Authors: Aru V, Sarais G, Savorani F, Engelsen SB, Cesare Marincola F Abstract This study investigated the effects of 48h heavy metal exposure upon the metabolic profiles of Ruditapes decussatus and Ruditapes philippinarum using (1)H NMR metabolomics. Both species were exposed to increasing concentrations of lead nitrate (10, 40, 60 and 100μg/L) and zinc chloride (20, 50, 100 and 150μg/L), under laboratory conditions. ICP-OES analysis was further performed on the clams' samples in order to verify the occurrence of heavy metal bioaccumulation. With respect to the controls, the metabolic profiles of treated R. decussatus exhibited higher levels of organic osmolytes and lower contents of free amino acids. An opposite behavior was shown by R. philippinarum. In terms of heavy metal, the exposure effects were more evident in the case of Pb rather than Zn. These findings show that NMR-based metabolomics has the required sensitivity and specificity for the identification of metabolites that can act as sensitive indicators of contaminant-induced stress. PMID: 27058966 [PubMed - as supplied by publisher]

metabolomics; +18 new citations

Sat, 09/04/2016 - 12:18
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 2016/04/09PubMed comprises more than 24 million 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.

Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever.

Fri, 08/04/2016 - 14:07
Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever. PLoS Negl Trop Dis. 2016 Apr;10(4):e0004607 Authors: Cui L, Lee YH, Thein TL, Fang J, Pang J, Ooi EE, Leo YS, Ong CN, Tannenbaum SR Abstract Effective triage of dengue patients early in the disease course for in- or out-patient management would be useful for optimal healthcare resource utilization while minimizing poor clinical outcome due to delayed intervention. Yet, early prognosis of severe dengue is hampered by the heterogeneity in clinical presentation and routine hematological and biochemical measurements in dengue patients that collectively correlates poorly with eventual clinical outcome. Herein, untargeted liquid-chromatography mass spectrometry metabolomics of serum from patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) in the febrile phase (<96 h) was used to globally probe the serum metabolome to uncover early prognostic biomarkers of DHF. We identified 20 metabolites that are differentially enriched (p<0.05, fold change >1.5) in the serum, among which are two products of tryptophan metabolism-serotonin and kynurenine. Serotonin, involved in platelet aggregation and activation decreased significantly, whereas kynurenine, an immunomodulator, increased significantly in patients with DHF, consistent with thrombocytopenia and immunopathology in severe dengue. To sensitively and accurately evaluate serotonin levels as prognostic biomarkers, we implemented stable-isotope dilution mass spectrometry and used convalescence samples as their own controls. DHF serotonin was significantly 1.98 fold lower in febrile compared to convalescence phase, and significantly 1.76 fold lower compared to DF in the febrile phase of illness. Thus, serotonin alone provided good prognostic utility (Area Under Curve, AUC of serotonin = 0.8). Additionally, immune mediators associated with DHF may further increase the predictive ability than just serotonin alone. Nine cytokines, including IFN-γ, IL-1β, IL-4, IL-8, G-CSF, MIP-1β, FGF basic, TNFα and RANTES were significantly different between DF and DHF, among which IFN-γ ranked top by multivariate statistics. Combining serotonin and IFN-γ improved the prognosis performance (AUC = 0.92, sensitivity = 77.8%, specificity = 95.8%), suggesting this duplex panel as accurate metrics for the early prognosis of DHF. PMID: 27055163 [PubMed - as supplied by publisher]

Effects of petrochemical contamination on caged marine mussels using a multi-biomarker approach: Histological changes, neurotoxicity and hypoxic stress.

Fri, 08/04/2016 - 14:07
Effects of petrochemical contamination on caged marine mussels using a multi-biomarker approach: Histological changes, neurotoxicity and hypoxic stress. Mar Environ Res. 2016 Mar 31; Authors: Maisano M, Cappello T, Natalotto A, Vitale V, Parrino V, Giannetto A, Oliva S, Mancini G, Cappello S, Mauceri A, Fasulo S Abstract This work was designed to evaluate the biological effects of petrochemical contamination on marine mussels. Mytilus galloprovincialis, widely used as sentinel organisms in biomonitoring studies, were caged at the "Augusta-Melilli-Priolo" industrial site (eastern Sicily, Italy), chosen as one of the largest petrochemical areas in Europe, and Brucoli, chosen as reference site. Chemical analyses of sediments at the polluted site revealed high levels of PAHs and mercury, exceeding the national and international guideline limits. In mussels from the polluted site, severe morphological alterations were observed in gills, mainly involved in nutrient uptake and gas exchange. Changes in serotonergic and cholinergic systems, investigated through immunohistochemical, metabolomics and enzymatic approaches, were highlighted in gills, as well as onset of hypoxic adaptive responses with up-regulation of hypoxia-inducible factor transcript. Overall, the application of a multi-biomarker panel results effective in assessing the biological effects of petrochemical contamination on the health of aquatic organisms. PMID: 27053509 [PubMed - as supplied by publisher]

Evaluation of 2,4-dichlorophenol exposure of Japanese medaka, Oryzias latipes, using a metabolomics approach.

Fri, 08/04/2016 - 14:07
Evaluation of 2,4-dichlorophenol exposure of Japanese medaka, Oryzias latipes, using a metabolomics approach. Environ Sci Pollut Res Int. 2016 Apr 7; Authors: Kokushi E, Shintoyo A, Koyama J, Uno S Abstract In this study, the metabolic effects of waterborne exposure of medaka (Oryzias latipes) to nominal concentrations of 20 (L group) and 2000 μg/L (H group) 2,4-dichlorophenol (DCP) were examined using a gas chromatography/mass spectroscopy (GC/MS) metabolomics approach. A principal component analysis (PCA) separated the L, H, and control groups along PC1 to explain the toxic effects of DCP at 24 h of exposure. Furthermore, the L and H groups were separated along PC1 at 96 h on the PCA score plots. These results suggest that the effects of DCP depended on exposure concentration and time. Changes in tricarboxylic cycle metabolites suggested that fish exposed to 2,4-DCP require more energy to metabolize and eliminate DCP, particularly at 96 h of exposure. A time-dependent response in the fish exposed to DCP was observed in the GC/MS data, suggesting that the higher DCP concentration had greater effects at 24 h than those observed in response to the lower concentration. In addition, several essential amino acids (arginine, histidine, lysine, isoleucine, leucine, methionine, phenylalanine, threonine, tryptophan, and valine) decreased after DCP exposure in the H group, and starvation condition and high concentration exposure of DCP could consume excess energy from amino acids. PMID: 27053050 [PubMed - as supplied by publisher]

Reply to the commentary by Law and Han: the importance of suitable GC-MS date processing and analysis for plant and environmental metabolomics, with references to: changes in the abundance of sugars and sugar-like compounds in tall fescue (Festuca...

Fri, 08/04/2016 - 14:07
Reply to the commentary by Law and Han: the importance of suitable GC-MS date processing and analysis for plant and environmental metabolomics, with references to: changes in the abundance of sugars and sugar-like compounds in tall fescue (Festuca arundinacea) due to growth in naphthalene-treated sand. Environ Sci Pollut Res Int. 2016 Apr 7; Authors: Balasubramaniyam A, Harvey PJ PMID: 27053046 [PubMed - as supplied by publisher]

HDL functionality in South Asians as compared to white Caucasians.

Fri, 08/04/2016 - 14:07
HDL functionality in South Asians as compared to white Caucasians. Nutr Metab Cardiovasc Dis. 2016 Feb 19; Authors: Bakker LE, Boon MR, Annema W, Dikkers A, van Eyk HJ, Verhoeven A, Mayboroda OA, Jukema JW, Havekes LM, Meinders AE, Willems van Dijk K, Jazet IM, Tietge UJ, Rensen PC Abstract BACKGROUND AND AIMS: South Asians have an exceptionally high risk of developing cardiovascular disease compared to white Caucasians. A contributing factor might be dysfunction of high density lipoprotein (HDL). We aimed to compare HDL function in different age groups of both ethnicities. METHODS AND RESULTS: HDL functionality with respect to cholesterol efflux, anti-oxidation and anti-inflammation was determined using fasting, apoB-depleted, plasma samples from South Asian and white Caucasian neonates (n = 14 each), adolescent healthy men (n = 12 each, 18-25 y), and adult overweight men (n = 12 each, 40-50 y). Adolescents were subjected to a 5-day high fat high calorie diet (HCD) and adults to an 8-day very low calorie diet (LCD). Additionally, HDL composition was measured in adolescents and adults using (1)H-NMR spectroscopy. Anti-oxidative capacity was lower in South Asian adults before LCD (19.4 ± 2.1 vs. 25.8 ± 1.2%, p = 0.045, 95%-CI = [0.1; 12.7]) and after LCD (16.4 ± 2.4 vs. 27.6 ± 2.7%, p = 0.001, 95%-CI = [4.9; 17.5]). Anti-inflammatory capacity was reduced in South Asian neonates (23.8 ± 1.2 vs. 34.9 ± 1.3%, p = 0.000001, 95%-CI = [-14.6; -7.5]), and was negatively affected by an 8-day LCD only in South Asian adults (-12.2 ± 4.3%, p = 0.005, 95%-CI = [-5.9; -1.2]). Cholesterol efflux capacity was increased in response to HCD in adolescents (South Asians: +6.3 ± 2.9%, p = 0.073, 95%-CI = [-0.02; 0.46], Caucasians: +11.8 ± 3.4%, p = 0.002, 95%-CI = [0.17;0.65]) and decreased after LCD in adults (South Asians: -10.3 ± 2.4%, p < 0.001, 95%-CI = [-0.57; -0.20], Caucasians: -13.7 ± 1.9%, p < 0.00001, 95%-CI = [-0.67; -0.33]). Although subclass analyses of HDL showed no differences between ethnicities, cholesterol efflux correlated best with cholesterol and phospholipid within small HDL compared to other HDL subclasses and constituents. CONCLUSION: Impaired HDL functionality in South Asians may be a contributing factor to their high CVD risk. CLINICAL TRIAL REGISTRATION: NTR 2473 (URL: http://www.trialregister.nl/). PMID: 27052926 [PubMed - as supplied by publisher]

Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk.

Fri, 08/04/2016 - 14:07
Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk. J Nutr. 2016 Apr 6; Authors: Trammell SA, Yu L, Redpath P, Migaud ME, Brenner C Abstract BACKGROUND: Nicotinamide riboside (NR) is a recently discovered NAD(+)precursor vitamin with a unique biosynthetic pathway. Although the presence of NR in cow milk has been known for more than a decade, the concentration of NR with respect to the other NAD(+)precursors was unknown. OBJECTIVE: We aimed to determine NAD(+)precursor vitamin concentration in raw samples of milk from individual cows and from commercially available cow milk. METHODS: LC tandem mass spectrometry and isotope dilution technologies were used to quantify NAD(+)precursor vitamin concentration and to measure NR stability in raw and commercial milk. Nuclear magnetic resonance (NMR) spectroscopy was used to test for NR binding to substances in milk. RESULTS: Cow milk typically contained ∼12 μmol NAD(+)precursor vitamins/L, of which 60% was present as nicotinamide and 40% was present as NR. Nicotinic acid and other NAD(+)metabolites were below the limits of detection. Milk from samples testing positive forStaphylococcus aureuscontained lower concentrations of NR (Spearman ρ = -0.58,P= 0.014), and NR was degraded byS. aureus Conventional milk contained more NR than milk sold as organic. Nonetheless, NR was stable in organic milk and exhibited an NMR spectrum consistent with association with a protein fraction in skim milk. CONCLUSIONS: NR is a major NAD(+)precursor vitamin in cow milk. Control ofS. aureusmay be important to preserve the NAD(+)precursor vitamin concentration of milk. PMID: 27052539 [PubMed - as supplied by publisher]

Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota during Catch-Up Growth in Undernourished Neonatal Mice.

Fri, 08/04/2016 - 14:07
Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota during Catch-Up Growth in Undernourished Neonatal Mice. J Nutr. 2016 Apr 6; Authors: Preidis GA, Ajami NJ, Wong MC, Bessard BC, Conner ME, Petrosino JF Abstract BACKGROUND: Protein-energy undernutrition during early development confers a lifelong increased risk of obesity-related metabolic disease. Mechanisms by which metabolic abnormalities persist despite catch-up growth are poorly understood. OBJECTIVE: We sought to determine whether abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice remain altered during catch-up growth. METHODS: Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. Both groups were weaned simultaneously to a standard unpurified diet. At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. RESULTS: Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinaryp-cresol sulfate concentrations than did controls. Plasma serotonin concentrations in undernourished mice were 25% lower at 0 wk but 1.5-fold higher than in controls at 3 wk. Whereas most urine and plasma metabolites normalized with refeeding, 117 fecal metabolites remained altered at 3 wk, including multipleN-linked glycans. Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). Abundances of the mucolytic organismsAkkermansia muciniphilaandMucispirillum schaedleriwere altered at 0 and 1 wk. Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P= 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P= 0.0006) than did controls. CONCLUSION: Microbial-derived metabolites and intestinal microbiota remain altered during catch-up growth in undernourished neonatal mice. PMID: 27052538 [PubMed - as supplied by publisher]

Study of Phospholipids in Single Cells Using an Integrated Microfluidic Device Combined with Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry.

Fri, 08/04/2016 - 14:07
Related Articles Study of Phospholipids in Single Cells Using an Integrated Microfluidic Device Combined with Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry. Anal Chem. 2015 Jul 21;87(14):7052-9 Authors: Xie W, Gao D, Jin F, Jiang Y, Liu H Abstract Single-cell trapping and high-throughput mass spectrometry analysis remain challenging now. Current technologies for single-cell analysis have several limitations, such as throughput, space resolution, and multicomponent analysis. In this study, we demonstrate, for the first time, the combination of microfluidic chip and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) for high-throughput and automatic single-cell phospholipids analysis. A microwell-array-based microfluidic chip was designed and fabricated for cell array formation on an indium tin oxide (ITO)-coated glass slide. Mass spectrometry imaging measurement with 25 μm pixel size was performed with a MALDI ion source. Eight phospholipids in a single A549 cell were detected, and their structures were further identified by MS/MS spectra. Selected ion images were generated with a bin width of Δm/z ± 0.005. The selected ion images and optical images of the cell array showed excellent correlation, and mass spectrometry information on phospholipids from 1-3 cells was extracted automatically by selecting pixels with the same fixed interval between microwells on the chip. The measurement and data extraction could be processed in several minutes to achieve a high-throughput analysis. Through the optimization of different microwell sizes and different matrices, this method showed potential for the analysis of other metabolites or metabolic changes at the single-cell level. PMID: 26110742 [PubMed - indexed for MEDLINE]

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