PubMed

Related Articles GeneNetwork: A Toolbox for Systems Genetics. Methods Mol Biol. 2017;1488:75-120 Authors: Mulligan MK, Mozhui K, Prins P, Williams RW Abstract The goal of systems genetics is to understand the impact of genetic variation across all levels of biological organization, from mRNAs, proteins, and metabolites, to higher-order physiological and behavioral traits. This approach requires the accumulation and integration of many types of data, and also requires the use of many types of statistical tools to extract relevant patterns of covariation and causal relations as a function of genetics, environment, stage, and treatment. In this protocol we explain how to use the GeneNetwork web service, a powerful and free online resource for systems genetics. We provide workflows and methods to navigate massive multiscalar data sets and we explain how to use an extensive systems genetics toolkit for analysis and synthesis. Finally, we provide two detailed case studies that take advantage of human and mouse cohorts to evaluate linkage between gene variants, addiction, and aging. PMID: 27933521 [PubMed - in process]

Related Articles Non-targeted Plasma Metabolome of Early and Late Lactation Gilts. Front Mol Biosci. 2016;3:77 Authors: Rempel LA, Miles JR, Oliver WT, Broeckling CD Abstract Female pigs nursing their first litter (first-parity gilts) have increased energy requirements not only to support their piglets, but they themselves are still maturing. Non-targeted plasma metabolomics were used to investigate the differences between (1) post-farrowing and weaning (early or late lactation), (2) degree of body condition loss after lactation (extreme or minimal), and (3) interactions; to potentially identify compounds or pathways that could aide in alleviating energetic demands of lactation in gilts. Twenty first-parity gilts were selected with similar (P ≥ 0.4475) number of piglets born and nursed, and similar (P ≥ 0.3141) body condition traits (e.g., body weight and backfat thickness) post-farrowing, yet exhibited minimal or extreme loss (P ≤ 0.0094) in body weight (8.6 ± 1.48 kg and 26.1 ± 1.90 kg, respectively) and backfat thickness (1.3 ± 0.67 mm and 4.7 ± 0.86 mm, respectively) following lactation (weaning). Plasma samples from first-parity gilts at post-farrowing and weaning were investigated using UPLC-MS and GC-MS to generate a comprehensive metabolic profile. Each approach yielded approximately 700 detected features. An ANOVA was performed on each detected compound in R for time of collection, body condition change, and the interaction, followed by a false discovery correction. Two unknown features were different (P ≤ 0.05) for extreme vs. minimal body condition change. Several compound differences (P ≤ 0.05) were identified between post-farrowing and weaning. Thirty-two features detected by UPLC-MS had at least a log2 fold-change of ±1.0 while only 18 features had a log2 fold-change of ±0.6 or more for the significant GC-MS features. Annotation implicated various metabolic pathways. Creatinine was greater at weaning (P = 0.0224) and others have reported increased serum concentrations of creatinine in response to body weight loss. Hippurate and caprolactam, associated with protein catabolism, were also greater (P ≤ 0.0166) at weaning. Phospholipid features (P ≤ 0.0347) and inositol-related features (P ≤ 0.0236) were also greater at weaning. Inositol features may exert insulin-like effects. The energetic demands of lactation in gilts nursing their first litter indicated a greater difference exists between early and late lactation regardless of body condition loss. PMID: 27933298 [PubMed - in process]

Related Articles Branched-Chain Amino Acid Levels Are Related with Surrogates of Disturbed Lipid Metabolism among Older Men. Front Med (Lausanne). 2016;3:57 Authors: Kujala UM, Peltonen M, Laine MK, Kaprio J, Heinonen OJ, Sundvall J, Eriksson JG, Jula A, Sarna S, Kainulainen H Abstract AIMS/HYPOTHESIS: Existing studies suggest that decreased branched-chain amino acid (BCAA) catabolism and thus elevated levels in blood are associated with metabolic disturbances. Based on such information, we have developed a hypothesis how BCAA degradation mechanistically connects to tricarboxylic acid cycle, intramyocellular lipid storage, and oxidation, thus allowing more efficient mitochondrial energy production from lipids as well as providing better metabolic health. We analyzed whether data from aged Finnish men are in line with our mechanistic hypothesis linking BCAA catabolism and metabolic disturbances. METHODS: Older Finnish men enriched with individuals having been athletes in young adulthood (n = 593; mean age 72.6 ± 5.9 years) responded to questionnaires, participated in a clinical examination including assessment of body composition with bioimpedance and gave fasting blood samples for various analytes as well as participated in a 2-h 75 g oral glucose tolerance test. Metabolomics measurements from serum included BCAAs (isoleucine, leucine, and valine). RESULTS: Out of the 593 participants, 59 had previously known type 2 diabetes, further 67 had screen-detected type 2 diabetes, 127 impaired glucose tolerance, and 125 impaired fasting glucose, while 214 had normal glucose regulation and one had missing glucose tolerance information. There were group differences in all of the BCAA concentrations (p ≤ 0.005 for all BCAAs), such that those with normal glucose tolerance had the lowest and those with diabetes mellitus had the highest BCAA concentrations. All BCAA levels correlated positively with body fat percentage (r = 0.29-0.34, p < 0.0001 for all). Expected associations with high BCAA concentrations and unfavorable metabolic profile indicators from metabolomics analysis were found. Except for glucose concentrations, the associations were stronger with isoleucine and leucine than with valine. CONCLUSION/INTERPRETATION: The findings provided further support for our hypothesis by strengthening the idea that the efficiency of BCAA catabolism may be mechanistically involved in the regulation of fat oxidation, thus affecting the levels of metabolic disease risk factors. PMID: 27933294 [PubMed - in process]

Related Articles Type 1 reaction in leprosy patients corresponds with a decrease in pro-resolving and an increase in pro-inflammatory lipid mediators. J Infect Dis. 2016 Dec 08;: Authors: Silva CA, Webb K, Andre BG, Marques MA, de Carvalho FM, de Macedo CS, Pinheiro RO, Sarno EN, Pessolani MC, Belisle JT Abstract BACKGROUND: Type 1 reaction (T1R) is an acute Th1 inflammatory episode in leprosy patients. While immunological responses associated with T1R have been investigated, the corresponding metabolic responses that could contribute to T1R pathology have received little attention. METHODS: Metabolomics-based analyses of sera from T1R (n=7) and T1R-free (n=9) patients were conducted via liquid chromatography-mass spectrometry (LC-MS). Serum metabolites that significantly differed (p<0.05) with a log2 fold change of ≥1.0 between patient groups were interrogated against known metabolic pathways. The structural identification of targeted metabolites were confirmed and abundance changes validated by mass spectrometry and enzyme-linked immunoassay (EIA). RESULTS: Forty metabolic pathways were perturbed in T1R patients, with 71 dysregulated metabolites mapping to pathways for lipid mediators of inflammation. Of note was an increase in the abundance of the pro-inflammatory leukotriene B4 (LTB4), and a corresponding decrease in pro-resolving resolvin D1 (RvD1). Also, levels of prostaglandin D2 (PGD2) and lipoxin A4 (LXA4) in T1R patients were significantly increased, while prostaglandin E2 (PGE2) was decreased. CONCLUSIONS: The dysregulation of metabolic pathways leading to abundance shifts between pro-inflammatory and pro-resolving lipid mediators provides a link between metabolic and cellular immune responses that result in the Th1-mediated pathology of T1R. PMID: 27932613 [PubMed - as supplied by publisher]

Related Articles Predictive diagnosis of major depression using NMR-based metabolomics and least-squares support vector machine. Clin Chim Acta. 2016 Dec 05;: Authors: Zheng H, Zheng P, Zhao L, Jia J, Tang S, Xu P, Xie P, Gao H Abstract BACKGROUND: Major depressive (MD) disorder is a serious psychiatric disorder that can result in suicidal behavior if not treated. The MD diagnosis using a standardized instrument instead of a structured interview will be advantageous for treatment and management of the MD, but so far no such technique exists. We developed an integrated analytical method of NMR-based metabolomics and least squares-support vector machine (LS-SVM) for predictive diagnosis of the MD. METHODS: The metabolite profiles in clinical plasma samples obtained from 72 depressive patients and 54 healthy subjects were analyzed by NMR spectroscopy. Then, LS-SVM models with different kernels were trained and tested using 80% and 20% of samples, respectively. RESULTS: We found that the best performance for the MD prediction was achieved by LS-SVM equipped with RBF kernel. Moreover, the predictive performance of the MD using multi-biomarkers was largely improved as compared with that using a single biomarker. In this study, the LS-SVM-RBF using glucose-lipid signaling can achieve the MD prediction with the AUC values of 0.94 (0.89-0.99) in the training set and 0.96 (0.92-1.00) in the test set. CONCLUSION: The LS-SVM-RBF using glucose-lipid signaling obtained from NMR spectroscopy can be used as an auxiliary diagnostic tool for the MD. PMID: 27931880 [PubMed - as supplied by publisher]

Related Articles Translational potential of long-term decreases in mitochondrial lipids in a mouse model of Gulf War Illness. Toxicology. 2016 Nov 30;372:22-33 Authors: Abdullah L, Evans JE, Joshi U, Crynen G, Reed J, Mouzon B, Baumann S, Montague H, Zakirova Z, Emmerich T, Bachmeier C, Klimas N, Sullivan K, Mullan M, Ait-Ghezala G, Crawford F Abstract Gulf War Illness (GWI) affects 25% of veterans from the 1990-1991 Gulf War (GW) and is accompanied by damage to the brain regions involved in memory processing. After twenty-five years, the chronic pathobiology of GWI is still unexplained. To address this problem, we examined the long-term consequences of GW exposures in an established GWI mouse model to identify biological processes that are relevant to the chronic symptoms of GWI. Three-month old male C57BL6 mice were exposed for 10days to GW agents (pyridostigmine bromide and permethrin). Barnes Maze testing conducted at 15- and 16-months post-exposure revealed learning and memory impairment. Immunohistochemical analyses showed astroglia and microglia activation in the hippocampi of exposed mice. Proteomic studies identified perturbation of mitochondria function and metabolomics data showed decreases in the Krebs cycle compounds, lactate, β-hydroxybutyrate and glycerol-3 phosphate in the brains of exposed mice. Lipidomics data showed decreases in fatty acids, acylcarnitines and phospholipids, including cardiolipins in the brains of exposed mice. Pilot biomarker studies showed that plasma from exposed mice and veterans with GWI had increases in odd-chain, and decreases in long-chain, acylcarnitines compared to their respective controls. Very long-chain acylcarnitines were decreased in veterans with GWI compared to controls. These studies suggest that mitochondrial lipid disturbances might be associated with GWI and that further investigation is required to determine its role in the pathophysiology of this illness. Targeting mitochondrial function may provide effective therapies for GWI, and that lipid abnormalities could serve as biomarkers of GWI. PMID: 27931520 [PubMed - in process]

Expanding the Klebsiella pneumoniae volatile metabolome using advanced analytical instrumentation for the detection of novel metabolites. J Appl Microbiol. 2016 Dec 08;: Authors: Rees CA, Franchina FA, Nordick KV, Kim PJ, Hill JE Abstract AIMS: The purpose of this study was to identify the volatile molecules produced by the pathogenic Gram-negative bacterium Klebsiella pneumoniae (ATCC 13883) during in vitro growth using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS). METHODS AND RESULTS: K. pneumoniae ATCC 13883 was incubated in lysogeny broth (LB) to mid-exponential and stationary growth phases. Headspace volatile molecules from culture supernatants were concentrated using solid-phase microextraction (SPME) and analyzed via GC×GC-TOFMS. Ninety-two K. pneumoniae-associated volatile molecules were detected, of which 78 (85%) were detected at both phases of growth and 14 (15%) were detected at either mid-exponential or stationary growth phases. CONCLUSIONS: This study has increased the total number of reported K. pneumoniae-associated volatile molecules from 77 to 150, demonstrating the sensitivity and resolution achieved by employing GC×GC-TOFMS for the analysis of bacterial headspace volatiles. SIGNIFICANCE AND IMPACT OF THE STUDY: This study represents an early-stage comprehensive volatile metabolomic analysis of an opportunistic bacterial pathogen. Characterizing the volatile molecules produced by K. pneumoniae during in vitro growth could provide us with a better understanding of this organisms' metabolism; an area that has not been extensively studied to-date. This article is protected by copyright. All rights reserved. PMID: 27930839 [PubMed - as supplied by publisher]

Inflammatory Bowel Disease Meets Systems Biology: A Multi-Omics Challenge and Frontier. OMICS. 2016 Dec;20(12):692-698 Authors: Palmieri O, Mazza T, Castellana S, Panza A, Latiano T, Corritore G, Andriulli A, Latiano A Abstract The inflammatory bowel disease (IBD) is a systemic disease that is characterized by the inflammation of the gastrointestinal tract. It includes ulcerative colitis and the Crohn's disease. Presently, IBD is one of the most investigated common complex human disorders, although its causes remain unclear. Multi-omics mechanisms involving genomic, transcriptomic, proteomic, and epigenomic variations, not to forget the miRNome, together with environmental contributions, result in an impairment of the immune system in persons with IBD. Such interactions at multiple levels of biology and in concert with the environment constitute the actual engine of this complex disease, demanding a multifactorial and multi-omics perspective to better understand the root causes of IBD. This expert analysis reviews and examines the latest literature and underscores, from the perspective of systems biology, the value of multi-omics technologies as opportunities to unravel the "IBD integrome." We anticipate that multi-omics research will accelerate the new discoveries and insights on IBD in the near future. It shall also pave the way for early diagnosis and help clinicians and families with IBD to forecast and make informed decisions about the prognosis and, possibly, personalized therapeutics in the future. PMID: 27930092 [PubMed - in process]

A Systematic Evaluation of Blood Serum and Plasma Pre-Analytics for Metabolomics Cohort Studies. Int J Mol Sci. 2016 Dec 05;17(12): Authors: Jobard E, Trédan O, Postoly D, André F, Martin AL, Elena-Herrmann B, Boyault S Abstract The recent thriving development of biobanks and associated high-throughput phenotyping studies requires the elaboration of large-scale approaches for monitoring biological sample quality and compliance with standard protocols. We present a metabolomic investigation of human blood samples that delineates pitfalls and guidelines for the collection, storage and handling procedures for serum and plasma. A series of eight pre-processing technical parameters is systematically investigated along variable ranges commonly encountered across clinical studies. While metabolic fingerprints, as assessed by nuclear magnetic resonance, are not significantly affected by altered centrifugation parameters or delays between sample pre-processing (blood centrifugation) and storage, our metabolomic investigation highlights that both the delay and storage temperature between blood draw and centrifugation are the primary parameters impacting serum and plasma metabolic profiles. Storing the blood drawn at 4 °C is shown to be a reliable routine to confine variability associated with idle time prior to sample pre-processing. Based on their fine sensitivity to pre-analytical parameters and protocol variations, metabolic fingerprints could be exploited as valuable ways to determine compliance with standard procedures and quality assessment of blood samples within large multi-omic clinical and translational cohort studies. PMID: 27929400 [PubMed - in process]

Metabolism of HT-2 Toxin and T-2 Toxin in Oats. Toxins (Basel). 2016 Dec 05;8(12): Authors: Meng-Reiterer J, Bueschl C, Rechthaler J, Berthiller F, Lemmens M, Schuhmacher R Abstract The Fusarium mycotoxins HT-2 toxin (HT2) and T-2 toxin (T2) are frequent contaminants in oats. These toxins, but also their plant metabolites, may contribute to toxicological effects. This work describes the use of (13)C-assisted liquid chromatography-high-resolution mass spectrometry for the first comprehensive study on the biotransformation of HT2 and T2 in oats. Using this approach, 16 HT2 and 17 T2 metabolites were annotated including novel glycosylated and hydroxylated forms of the toxins, hydrolysis products, and conjugates with acetic acid, putative malic acid, malonic acid, and ferulic acid. Further targeted quantitative analysis was performed to study toxin metabolism over time, as well as toxin and conjugate mobility within non-treated plant tissues. As a result, HT2-3-O-β-d-glucoside was identified as the major detoxification product of both parent toxins, which was rapidly formed (to an extent of 74% in HT2-treated and 48% in T2-treated oats within one day after treatment) and further metabolised. Mobility of the parent toxins appeared to be negligible, while HT2-3-O-β-d-glucoside was partly transported (up to approximately 4%) through panicle side branches and stem. Our findings demonstrate that the presented combination of untargeted and targeted analysis is well suited for the comprehensive elucidation of mycotoxin metabolism in plants. PMID: 27929394 [PubMed - in process]

Related Articles Metabolic Profiling Reveals Differences in Plasma Concentrations of Arabinose and Xylose after Consumption of Fiber-Rich Pasta and Wheat Bread with Differential Rates of Systemic Appearance of Exogenous Glucose in Healthy Men. J Nutr. 2016 Dec 07;: Authors: Pantophlet AJ, Wopereis S, Eelderink C, Vonk RJ, Stroeve JH, Bijlsma S, van Stee L, Bobeldijk I, Priebe MG Abstract BACKGROUND: The consumption of products rich in cereal fiber and with a low glycemic index is implicated in a lower risk of metabolic diseases. Previously, we showed that the consumption of fiber-rich pasta compared with bread resulted in a lower rate of appearance of exogenous glucose and a lower glucose clearance rate quantified with a dual-isotope technique, which was in accordance with a lower insulin and glucose-dependent insulinotropic polypeptide response. OBJECTIVE: To gain more insight into the acute metabolic consequences of the consumption of products resulting in differential glucose kinetics, postprandial metabolic profiles were determined. METHODS: In a crossover study, 9 healthy men [mean ± SEM age: 21 ± 0.5 y; mean ± SEM body mass index (kg/m(2)): 22 ± 0.5] consumed wheat bread (132 g) and fresh pasta (119 g uncooked) enriched with wheat bran (10%) meals. A total of 134 different metabolites in postprandial plasma samples (at -5, 30, 60, 90, 120, and 180 min) were quantified by using a gas chromatography-mass spectrometry-based metabolomics approach (secondary outcomes). Two-factor ANOVA and advanced multivariate statistical analysis (partial least squares) were applied to detect differences between both food products. RESULTS: Forty-two different postprandial metabolite profiles were identified, primarily representing pathways related to protein and energy metabolism, which were on average 8% and 7% lower after the men consumed pasta rather than bread, whereas concentrations of arabinose and xylose were 58% and 53% higher, respectively. Arabinose and xylose are derived from arabinoxylans, which are important components of wheat bran. The higher bioavailability of arabinose and xylose after pasta intake coincided with a lower rate of appearance of glucose and amino acids. We speculate that this higher bioavailability is due to higher degradation of arabinoxylans by small intestinal microbiota, facilitated by the higher viscosity of arabinoxylans after pasta intake than after bread intake. CONCLUSION: This study suggests that wheat bran, depending on the method of processing, can increase the viscosity of the meal bolus in the small intestine and interfere with macronutrient absorption in healthy men, thereby influencing postprandial glucose and insulin responses. This trial was registered at www.controlled-trials.com as ISRCTN42106325. PMID: 27927976 [PubMed - as supplied by publisher]

Related Articles Tumour biomarkers: homeostasis as a novel prognostic indicator. Open Biol. 2016 Dec;6(12): Authors: Falco M, Palma G, Rea D, De Biase D, Scala S, D'Aiuto M, Facchini G, Perdonà S, Barbieri A, Arra C Abstract The term 'personalized medicine' refers to a medical procedure that consists in the grouping of patients based on their predicted individual response to therapy or risk of disease. In oncologic patients, a 'tailored' therapeutic approach may potentially improve their survival and well-being by not only reducing the tumour, but also enhancing therapeutic response and minimizing the adverse effects. Diagnostic tests are often used to select appropriate and optimal therapies that rely both on patient genome and other molecular/cellular analysis. Several studies have shown that lifestyle and environmental factors can influence the epigenome and that epigenetic events may be involved in carcinogenesis. Thus, in addition to traditional biomarkers, epigenetic factors are raising considerable interest, because they could potentially be used as an excellent tool for cancer diagnosis and prognosis. In this review, we summarize the role of conventional cancer genetic biomarkers and their association with epigenomics. Furthermore, we will focus on the so-called 'homeostatic biomarkers' that result from the physiological response to cancer, emphasizing the concept that an altered 'new' homeostasis influence not only tumour environment, but also the whole organism. PMID: 27927793 [PubMed - in process]

Related Articles Metabolic and functional characterization of effects of developmental temperature in Drosophila melanogaster. Am J Physiol Regul Integr Comp Physiol. 2016 Dec 07;:ajpregu.00268.2016 Authors: Schou MF, Kristensen TN, Pedersen A, Karlsson GB, Loeschcke V, Malmendal A Abstract The ability of ectotherms to respond to changes in their thermal environment through plastic mechanisms is central to their adaptive capability. However, we still lack knowledge on physiological and functional responses by which ectotherms acclimate to temperatures during development, and in particular, how physiological stress at extreme temperatures may counteract beneficial acclimation responses at benign temperatures. We exposed Drosophila melanogaster to ten developmental temperatures covering their entire permissible temperature range. We obtained metabolic profiles and reaction norms for several functional traits: egg-to-adult viability, developmental time, and heat and cold tolerance. Females were more heat tolerant than males, whereas no sexual dimorphism was found in cold tolerance. A group of metabolites, mainly free amino acids, had linear reaction norms. Several energy carrying molecules, as well as some sugars, showed distinct inverted u-shaped norms of reaction across the thermal range, resulting in a positive correlation between metabolite intensities and egg-to-adult viability. At extreme temperatures, low levels of these metabolites were interpreted as a response characteristic of costs of homeostatic perturbations. Our results provide novel insights into a range of metabolites reported to be central for the acclimation response, and suggest several new candidate metabolites. Low and high temperatures result in different adaptive physiological responses, but they also have commonalities likely to be a result of the failure to compensate for the physiological stress. We suggest that the regulation of metabolites that are tightly connected to the performance curve is important for the ability of ectotherms to cope with variation in temperature. PMID: 27927623 [PubMed - as supplied by publisher]

Discovery and identification of potential biomarkers for alcohol-induced oxidative stress based on cellular metabolomics. Biomed Chromatogr. 2016 Dec 07;: Authors: Hu Q, Wei J, Liu Y, Fei X, Hao Y, Pei D, Di D Abstract Biomarkers involved in alcohol-induced oxidative stress play an important role in alcoholic liver disease prevention and diagnosis. Alcohol-induced oxidative stress in human liver L-02 cells was used to discover the potential biomarkers. Metabolites from L-02 cells induced by alcohol were measured by high-performance liquid chromatography and mass spectrometry. Fourteen metabolites that allowed discrimination between control and model groups were discovered by multivariate statistical data analysis (i.e. principal components analysis, orthogonal partial least-squares discriminate analysis). Based on the retention time, UV spectrum and LC-MS findings of the samples and compared with the authentic standards, eight biomarkers involved in alcohol-induced oxidative stress, namely, malic acid, oxidized glutathione, reduced glutathione, adenosine triphosphate, phenylalanine, adenosine monophosphate, nitrotyrosine, and tryptophan, were identified. These biomarkers offered important targets for disease diagnosis and other researches. PMID: 27925248 [PubMed - as supplied by publisher]

Production of Phloroglucinol, a Platform Chemical, in Arabidopsis using a Bacterial Gene. Sci Rep. 2016 Dec 07;6:38483 Authors: Abdel-Ghany SE, Day I, Heuberger AL, Broeckling CD, Reddy AS Abstract Phloroglucinol (1,3,5-trihydroxybenzene; PG) and its derivatives are phenolic compounds that are used for various industrial applications. Current methods to synthesize PG are not sustainable due to the requirement for carbon-based precursors and co-production of toxic byproducts. Here, we describe a more sustainable production of PG using plants expressing a native bacterial or a codon-optimized synthetic PhlD targeted to either the cytosol or chloroplasts. Transgenic lines were analyzed for the production of PG using gas and liquid chromatography coupled to mass spectroscopy. Phloroglucinol was produced in all transgenic lines and the line with the highest PhlD transcript level showed the most accumulation of PG. Over 80% of the produced PG was glycosylated to phlorin. Arabidopsis leaves have the machinery to glycosylate PG to form phlorin, which can be hydrolyzed enzymatically to produce PG. Furthermore, the metabolic profile of plants with PhlD in either the cytosol or chloroplasts was altered. Our results provide evidence that plants can be engineered to produce PG using a bacterial gene. Phytoproduction of PG using a bacterial gene paves the way for further genetic manipulations to enhance the level of PG with implications for the commercial production of this important platform chemical in plants. PMID: 27924918 [PubMed - in process]

Longitudinal study of pesticide residue levels in human milk from Western Australia during 12 months of lactation: Exposure assessment for infants. Sci Rep. 2016 Dec 07;6:38355 Authors: Du J, Gridneva Z, Gay MC, Lai CT, Trengove RD, Hartmann PE, Geddes DT Abstract The presence of pesticides in human milk (HM) is of great concern due to the potential health effects for the breastfed infant. To determine the relationships between HM pesticides and infant growth and development, a longitudinal study was conducted. HM samples (n = 99) from 16 mothers were collected at 2, 5, 9 and 12 months of lactation. A validated QuEChERS method and Gas chromatography-tandem mass spectrometry (GC-MS/MS) were used for the analysis of 88 pesticides in HM. Only p,p'-DDE, p,p'-DDT and β-HCH were detected with a mean concentration (±SD) of 52.25 ± 49.88 ng/g fat, 27.67 ± 20.96 ng/g fat and 48.00 ± 22.46 ng/g fat respectively. The concentrations of the detected pesticides decreased significantly throughout the first year of lactation. No significant relationships between HM p,p'-DDE and infant growth outcomes: weight, length, head circumference and percentage fat mass were detected. The actual daily intake (ADI) of total DDTs in this cohort was 14-1000 times lower than the threshold reference and significantly lower than the estimated daily intake (EDI). Further, the ADI decreased significantly throughout the first 12 months of lactation. PMID: 27924835 [PubMed - in process]

Metabolomics of Healthy Berry Fruits. Curr Med Chem. 2016 Dec 05; Authors: D Urso G, Piacente S, Pizza C, Montoro P Abstract The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome¬ databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations. PMID: 27924727 [PubMed - as supplied by publisher]

Related Articles NMR-Based Metabolomics of Oral Biofluids. Methods Mol Biol. 2017;1537:79-105 Authors: Schirra HJ, Ford PJ Abstract NMR-based metabolomics is an established technique for characterizing the metabolite profile of biological fluids and investigating how metabolite profiles change in response to biological and/or clinical stimuli. Thus, NMR-based metabolomics has the potential to discover biomarkers for diagnosis, prognosis, and/or therapy of clinical conditions, as well as to unravel the physiology underlying clinical conditions. Here, we describe a detailed protocol for NMR-based metabolomics of oral biofluids, including sample collection, sample handling, NMR data acquisition, and processing. In addition, we give a general overview of the statistical analysis of the resulting metabolomic data. PMID: 27924589 [PubMed - in process]

Related Articles Autopiquer - a Robust and Reliable Peak Detection Algorithm for Mass Spectrometry. J Am Soc Mass Spectrom. 2016 Dec 06; Authors: Kilgour DP, Hughes S, Kilgour SL, Mackay CL, Palmblad M, Tran BQ, Goo YA, Ernst RK, Clarke DJ, Goodlett DR Abstract We present a simple algorithm for robust and unsupervised peak detection by determining a noise threshold in isotopically resolved mass spectrometry data. Solving this problem will greatly reduce the subjective and time-consuming manual picking of mass spectral peaks and so will prove beneficial in many research applications. The Autopiquer approach uses autocorrelation to test for the presence of (isotopic) structure in overlapping windows across the spectrum. Within each window, a noise threshold is optimized to remove the most unstructured data, whilst keeping as much of the (isotopic) structure as possible. This algorithm has been successfully demonstrated for both peak detection and spectral compression on data from many different classes of mass spectrometer and for different sample types, and this approach should also be extendible to other types of data that contain regularly spaced discrete peaks. Graphical Abstract ᅟ. PMID: 27924495 [PubMed - as supplied by publisher]

Related Articles Early Diagnosis of Brain Metastases Using a Biofluids-Metabolomics Approach in Mice. Theranostics. 2016;6(12):2161-2169 Authors: Larkin JR, Dickens AM, Claridge TD, Bristow C, Andreou K, Anthony DC, Sibson NR Abstract Over 20% of cancer patients will develop brain metastases. Prognosis is currently extremely poor, largely owing to late-stage diagnosis. We hypothesized that biofluid metabolomics could detect tumours at the micrometastatic stage, prior to the current clinical gold-standard of blood-brain barrier breakdown. Metastatic mammary carcinoma cells (4T1-GFP) were injected into BALB/c mice via intracerebral, intracardiac or intravenous routes to induce differing cerebral and systemic tumour burdens. B16F10 melanoma and MDA231BR-GFP human breast carcinoma cells were used for additional modelling. Urine metabolite composition was analysed by (1)H NMR spectroscopy. Statistical pattern recognition and modelling was applied to identify differences or commonalities indicative of brain metastasis burden. Significant metabolic profile separations were found between control cohorts and animals with tumour burdens at all time-points for the intracerebral 4T1-GFP time-course. Models became stronger, with higher sensitivity and specificity, as the time-course progressed indicating a more severe tumour burden. Sensitivity and specificity for predicting a blinded testing set were 0.89 and 0.82, respectively, at day 5, both rising to 1.00 at day 35. Significant separations were also found between control and all 4T1-GFP injected mice irrespective of route. Likewise, significant separations were observed in B16F10 and MDA231BR-GFP cell line models. Metabolites underpinning each separation were identified. These findings demonstrate that brain metastases can be diagnosed in an animal model based on urinary metabolomics from micrometastatic stages. Furthermore, it is possible to separate differing systemic and CNS tumour burdens, suggesting a metabolite fingerprint specific to brain metastasis. This method has strong potential for clinical translation. PMID: 27924154 [PubMed - in process]