PubMed

Related Articles Obesity aggravates toxic effect of BPA on spermatogenesis. Environ Int. 2017 May 11;105:56-65 Authors: Hu W, Dong T, Wang L, Guan Q, Song L, Chen D, Zhou Z, Chen M, Xia Y, Wang X Abstract Both bisphenol A (BPA) and obesity affect male reproductive system. However, whether there is an interaction between them remains poorly understood. The aim of the present study was to evaluate the interaction between BPA exposure and obesity on semen quality and elucidate the mechanism in humans and animals. We firstly analyzed the interaction on semen volume, sperm count per ejaculate, sperm concentration and sperm motility in 357 men, and found that urinary BPA concentration was significantly correlated with sperm count per ejaculate in obese men (β=-34.62; 95% CI: -60.75, -8.48; P=0.01). Then we validated the interaction using lean and obese mice with administration of BPA. Significant interactions between BPA exposure and obesity on sperm count and sperm concentration was observed in mice. Finally, we conducted metabolomics analyses to identify metabolites related to the interaction. Metabolites related to the interaction, including capric acid, dodecanoic acid, l-palmitoylcarnitine, niacinamide, etc., are known to play critical roles in fatty acid oxidation and tricarboxylic acid cycle indicating increased oxidative stress associated with male reproductive dysfunction. Thus, our study finds an interaction between BPA exposure and obesity on sperm count and reveals potential metabolic mechanisms. It emphasizes the importance to study interactions between endocrine disrupting chemicals and obesity, and opens avenues for the possible use of animal models in identifying the interactions. PMID: 28501790 [PubMed - as supplied by publisher]

Related Articles Metabolite profile of koji amazake and its lactic acid fermentation product by Lactobacillus sakei UONUMA. J Biosci Bioeng. 2017 May 10;: Authors: Oguro Y, Nishiwaki T, Shinada R, Kobayashi K, Kurahashi A Abstract The koji amazake is a traditional sweet Japanese beverage. It has been consumed for over a thousand years in Japan; nonetheless, little is yet known of the ingredients in koji amazake. Therefore, this study aimed to analyze the metabolites of koji amazake using a metabolomics approach. Additionally, we reformed the flavor of koji amazake by lactic acid fermentation (LAF-amazake) using Lactobacillus sakei UONUMA, which was isolated from snow caverns. The purpose of this article is to identify the ingredients in these beverages. In LAF-amazake and koji amazake, sugars, amino acids, organic acids, and vitamin B complex were determined in the two beverages, and over 300 compounds were detected in total. Thirteen saccharides were identified including two unknown trisaccharides, and there were no differences in these between the two beverages. In LAF-amazake, lactic acid, vitamin B2 (riboflavin), B3 (nicotinic acid and nicotinamide), and B6 (pyridoxine) were significantly increased as compared to koji amazake, whereas malate and glutamine decreased. These results suggested that LAF, malolactic fermentation, and glutamine deamidation occurred simultaneously in LAF-amazake. L. sakei UONUMA strains produced these vitamins. Moreover, it was surprising that acetylcholine, a well-known neurotransmitter, was newly generated in LAF-amazake. Here, we have succeeded in reforming the flavor of koji amazake and obtained these metabolic data on the two beverages. The present study could provide useful basic information for promoting functional analyses of koji amazake and LAF-amazake for human health. PMID: 28501542 [PubMed - as supplied by publisher]

Related Articles Lipase-catalyzed kinetic resolution as key step in the synthesis of enantiomerically pure σ ligands with 2-benzopyran structure. Bioorg Med Chem. 2017 Apr 30;: Authors: Knappmann I, Lehmkuhl K, Köhler J, Schepmann D, Giera M, Bracher F, Wünsch B Abstract In order to obtain enantiomerically pure σ1 receptor ligands with a 2-benzopyran scaffold an Oxa-Pictet-Spengler reaction with the enantiomerically pure 2-phenylethanol derivatives (R)-4 and (S)-4 was envisaged. The kinetic resolution of racemic alcohol (±)-4 using Amano Lipase PS-C II and isopropenyl acetate in tert-butyl methyl ether led to the (R)-configured alcohol (R)-4 in 42% yield with an enantiomeric excess of 99.6%. The (S)-configured alcohol (S)-4 was obtained by Amano Lipase PS-C II catalyzed hydrolysis of enantiomerically enriched acetate (S)-5 (76.9% ee) and provided (S)-4 in 26% yield and 99.7% ee. The absolute configuration of alcohol (R)-4 was determined by exciton coupled CD spectroscopy of the bis(bromobenzoate) (R)-7. The next important step for the synthesis of 2-benzopyrans 2 and 3 was the Oxa-Pictet-Spengler reaction of the enantiomerically pure alcohols (R)-4 and (S)-4 with piperidone ketal 8 and chloropropionaldehyde acetal 12. The conformationally restricted spirocyclic 2-benzopyrans 2 revealed higher σ1 affinity than the more flexible aminoethyl derivatives 3. The (R)- and (R,R)-configured enantiomers (R)-2 and (R,R)-3 represent the eutomers of this class of compounds with eudismic ratios of 4.8 (2b) and 4.5 (2c). High σ1/σ2 selectivity (>49) was found for the most potent σ1 ligands (R)-2b, (R)-2c, (R)-2d, and (S)-2d (Ki(σ1) 9-15nM). PMID: 28501431 [PubMed - as supplied by publisher]

Related Articles Capillary electrophoresis tandem mass spectrometry determination of glutamic acid and homocysteine's metabolites: Potential biomarkers of amyotrophic lateral sclerosis. Talanta. 2017 Aug 01;170:63-68 Authors: Cieslarova Z, Lopes FS, do Lago CL, França MC, Colnaghi Simionato AV Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both lower and upper motor neurons, leading to muscle atrophy, paralysis, and death caused by respiratory failure or infectious complications. Altered levels of homocysteine, cysteine, methionine, and glutamic acid have been observed in plasma of ALS patients. In this context, a method for determination of these potential biomarkers in plasma by capillary electrophoresis tandem mass spectrometry (CE-MS/MS) is proposed herein. Sample preparation was carefully investigated, since sulfur-containing amino acids may interact with plasma proteins. Owing to the non-thiol sulfur atom in methionine, it was necessary to split sample preparation into two methods: i) determination of homocysteine and cysteine as S-acetyl amino acids; ii) determination of glutamic acid and methionine. All amino acids were separated within 25min by CE-MS/MS using 5molL(-1) acetic acid as background electrolyte and 5mmolL(-1) acetic acid in 50% methanol/H2O (v/v) as sheath liquid. The proposed CE-MS/MS method was validated, presenting RSD values below 6% and 11% for intra- and inter-day precision, respectively, for the middle concentration level within the linear range. The limits of detection ranged from 35 (homocysteine) to 268nmolL(-1) (glutamic acid). The validated method was applied to the analysis of plasma samples from a group of healthy individuals and patients with ALS, showing the potential of glutamic acid and homocysteine metabolites as biomarkers of ALS. PMID: 28501214 [PubMed - in process]

Related Articles Serum metabolomics reveals the mechanistic role of functional foods and exercise for obesity management in rats. J Pharm Biomed Anal. 2017 May 01;142:91-101 Authors: Ammar NM, Farag MA, Kholeif TE, Metwally NS, El-Sheikh NM, El Gendy AN, Abdel-Hamid AZ Abstract Obesity is one of the independent risk factors for several health problems, leading to metabolic perturbations and for which analytical approaches i.e., "metabolomics" is needed to monitor the underlying metabolic changes. In this study, obesity associated changes were assessed via serum metabolites analysis of obese rats fed on high fat diet. Obese rats were subsequently treated with different functional foods used for obesity management including pomegranate, grapefruit, and red cabbage in parallel to swimming exercise. Serum samples were analyzed using gas chromatography-mass spectrometry (GC-MS) followed by multivariate data analysis to classify samples and determine if such treatments can help revert obesity related metabolic changes back to normal status. Results led to the identification of several novel metabolites biomarkers for obesity related to lipids, amino acids and central tricarboxylic acid (TCA) pathways. Distinct variations in metabolite levels were recorded in obese rats compared to normal ones including l-aspartic, l-alanine, l-glutamine, l-glycine, phenylethanolamine, α-aminobutyric acid and β-hydroxybutyric acid. Metabolomics approach developed herein provides novel insight onto the metabolic disturbances associated with obesity, which will assist in future drug design that can help mitigate against such changes. PMID: 28500980 [PubMed - as supplied by publisher]

Related Articles High throughput metabolic profiling based on small amount of hepatic cells. Electrophoresis. 2017 May 12;: Authors: Zhou L, Yin P, Luo P, Tang L, Wang Z, Gao P, Piao H, Lu X, Xu G Abstract Common metabolomics platforms require about 10(6) cells, which has a limited throughput due to the time-consuming steps of cell culture and preparation. There is a demand for metabolic profiling methods to improve analytical throughput and detection sensitivity based on small amount of cells. In this study, we proposed a high-throughput scheme, integrating 96-well plate cell cultivation, in-situ cell pretreatment and sensitive dansylation labelling coupled with liquid chromatography-mass spectrometry analysis of metabolites inside hepG2 cells (of the order of magnitude of 10(3) cells in each well). A simple and rapid cell pretreatment was performed showing good extraction efficiency and good precision (the relative standard deviations smaller than 5%) for polar metabolites. The recovery in metabolite extraction evaluated with three isotope-labeled amino acids was from 89.7% to 106.3% at low, medium and high concentrations. The suitability of the method was illustrated by exploring influences of different fatty acids on HepG2 cells. This article is protected by copyright. All rights reserved. PMID: 28500646 [PubMed - as supplied by publisher]

Related Articles Comparative Metabolomic Analysis of the Green Microalga Chlorella sorokiniana Cultivated in the Single Culture and a Consortium with Bacteria for Wastewater Remediation. Appl Biochem Biotechnol. 2017 May 12;: Authors: Chen T, Zhao Q, Wang L, Xu Y, Wei W Abstract Co-culture of microalgae with many types of bacteria usually comes out with significant different treatment efficiencies for COD, nitrogen, and phosphorus in wastewater remediation, compared with the single culture. In order to understand the mechanism behind, a comparative experiment was designed in this study, using the green microalgae species Chlorella sorokiniana in the single culture and a consortium with a bacterium, Pseudomonas H4, for nutrient removal. Comparative metabolome profile analysis was conducted to reveal the Chlorella cell responses to the synergistic growth with the bacteria, and possible relations between the metabolic regulation of microalgae and the nutrient degradation were discussed. The detectable differential metabolites of Chlorella belonged to several classes, including carbohydrates, fatty acids, amino acids, phosphates, polyols, etc. The orthogonal partial least squares discriminant analysis (OPLS-DA) model of the identified metabolites suggests the metabolism in this alga was significantly affected by the bacteria, corresponding to different treatment behaviors. PMID: 28500414 [PubMed - as supplied by publisher]

Related Articles Thermal adaptation strategies of the extremophile bacterium Thermus filiformis based on multi-omics analysis. Extremophiles. 2017 May 12;: Authors: Mandelli F, Couger MB, Paixão DAA, Machado CB, Carnielli CM, Aricetti JA, Polikarpov I, Prade R, Caldana C, Paes Leme AF, Mercadante AZ, Riaño-Pachón DM, Squina FM Abstract Thermus filiformis is an aerobic thermophilic bacterium isolated from a hot spring in New Zealand. The experimental study of the mechanisms of thermal adaptation is important to unveil response strategies of the microorganism to stress. In this study, the main pathways involved on T. filiformis thermoadaptation, as well as, thermozymes with potential biotechnological applications were revealed based on omics approaches. The strategy adopted in this study disclosed that pathways related to the carbohydrate metabolism were affected in response to thermoadaptation. High temperatures triggered oxidative stress, leading to repression of genes involved in glycolysis and the tricarboxylic acid cycle. During heat stress, the glucose metabolism occurred predominantly via the pentose phosphate pathway instead of the glycolysis pathway. Other processes, such as protein degradation, stringent response, and duplication of aminoacyl-tRNA synthetases, were also related to T. filiformis thermoadaptation. The heat-shock response influenced the carotenoid profile of T. filiformis, favoring the synthesis of thermozeaxanthins and thermobiszeaxanthins, which are related to membrane stabilization at high temperatures. Furthermore, antioxidant enzymes correlated with free radical scavenging, including superoxide dismutase, catalase and peroxidase, and metabolites, such as oxaloacetate and α-ketoglutarate, were accumulated at 77 °C. PMID: 28500387 [PubMed - as supplied by publisher]

Related Articles The association of the lipidomic profile with features of polycystic ovary syndrome. J Mol Endocrinol. 2017 May 12;: Authors: Moran L, Mundra P, Teede H, Miekle PJ Abstract Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-aged women with reproductive and metabolic complications. While lipidomics can identify associations between lipid species and metabolic diseases, no research has examined the association of lipid species with the pathophysiological features of PCOS. The aim of this study was to examine the lipidomic profile in women with and without PCOS. This study was a cross-sectional study in 156 age-matched pre-menopausal women (18-45 years, BMI>25 kg/m2; n=92 with PCOS, n=64 without PCOS). Outcomes included the association between the plasma lipidomic profile [325 lipid species (24 classes) using liquid chromatography mass spectrometry] and PCOS, adiposity, homeostasis assessment of insulin resistance (HOMA), sex-hormone binding globulin (SHBG) and free androgen index (FAI). There were no associations of the lipidomic profile with PCOS or testosterone. HOMA was positively associated with 2 classes (dihydroceramide and triacylglycerol), SHBG was inversely associated with 2 classes (diacylglycerol and triacylglycerol), FAI was positively associated with 8 classes (ceramide, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylinositol, diacylglycerol and triacylglycerol) and waist circumference was associated with 8 classes [4 positively (dihydroceramide, phosphatidylglycerol, diacylglycerol and triacylglycerol) and 4 inversely [trihexosylceramide, GM3 ganglioside, alkenylphosphatidylcholine and alkylphosphatidylethanolamine]). The lipidomic profile was primarily related to central adiposity and FAI in women with or without PCOS. This supports prior findings that adiposity is a key driver of dyslipidaemia in PCOS and highlights the need for weight management through lifestyle interventions. PMID: 28500248 [PubMed - as supplied by publisher]

Related Articles Integration of gel-based and gel-free proteomic data for functional analysis of proteins through Soybean Proteome Database. J Proteomics. 2017 May 09;: Authors: Komatsu S, Wang X, Yin X, Nanjo Y, Ohyanagi H, Sakata K Abstract The Soybean Proteome Database (SPD) stores data on soybean proteins obtained with gel-based and gel-free proteomic techniques. The database was constructed to provide information on proteins for functional analyses. The majority of the data is focused on soybean (Glycine max 'Enrei'). The growth and yield of soybean are strongly affected by environmental stresses such as flooding. The database was originally constructed using data on soybean proteins separated by two-dimensional polyacrylamide gel electrophoresis, which is a gel-based proteomic technique. Since 2015, the database has been expanded to incorporate data obtained by label-free mass spectrometry-based quantitative proteomics, which is a gel-free proteomic technique. Here, the portions of the database consisting of gel-free proteomic data are described. The gel-free proteomic database contains 39,212 proteins identified in 63 sample sets, such as temporal and organ-specific samples of soybean plants grown under flooding stress or non-stressed conditions. In addition, data on organellar proteins identified in mitochondria, nuclei, and endoplasmic reticulum are stored. Furthermore, the database integrates multiple omics data such as genomics, transcriptomics, metabolomics, and proteomics. The SPD database is accessible at http://proteome.dc.affrc.go.jp/Soybean/. BIOLOGICAL SIGNIFICANCE: The Soybean Proteome Database stores data obtained from both gel-based and gel-free proteomic techniques. The gel-free proteomic database comprises 39,212 proteins identified in 63 sample sets, such as different organs of soybean plants grown under flooding stress or non-stressed conditions in a time-dependent manner. In addition, organellar proteins identified in mitochondria, nuclei, and endoplasmic reticulum are stored in the gel-free proteomics database. A total of 44,704 proteins, including 5490 proteins identified using a gel-based proteomic technique, are stored in the SPD. It accounts for approximately 80% of all predicted proteins from genome sequences, though there are over lapped proteins. Based on the demonstrated application of data stored in the database for functional analyses, it is suggested that these data will be useful for analyses of biological mechanisms in soybean. Furthermore, coupled with recent advances in information and communication technology, the usefulness of this database would increase in the analyses of biological mechanisms. PMID: 28499913 [PubMed - as supplied by publisher]

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Related Articles Persistently Altered Metabolic Phenotype following Perinatal Excitotoxic Brain Injury. Dev Neurosci. 2017 May 12;: Authors: Blaise BJ, Schwendimann L, Chhor V, Degos V, Hodson MP, Dallmann G, Keller M, Gressens P, Fleiss B Abstract Excitotoxicity plays a key role during insults to the developing brain such as neonatal encephalopathy, stroke, and encephalopathy of prematurity. Such insults affect many thousands of infants each year. Excitotoxicity causes frank lesions due to cell death and gliosis and disturbs normal developmental process, leading to deficits in learning, memory, and social integration that persist into adulthood. Understanding the underlying processes of the acute effects of excitotoxicity and its persistence during brain maturation provides an opportunity to identify mechanistic or diagnostic biomarkers, thus enabling and designing possible therapies. We applied mass spectrometry to provide metabolic profiles of brain tissue and plasma over time following an excitotoxic lesion (intracerebral ibotenate) to the neonatal (postnatal day 5) mouse brain. We found no differences between the plasma from the control (PBS-injected) and excitotoxic (ibotenate-injected) groups over time (on postnatal days 8, 9, 10, and 30). In the brain, we found that variations in amino acids (arginine, glutamine, phenylananine, and proline) and glycerophospholipids were sustaining acute and delayed (tertiary) responses to injury. In particular, the effect of the excitotoxic lesion on the normal profile of development was linked to alterations in a fingerprint of glycerophospolipids and amino acids. Specifically, we identified increases in the amino acids glutamine, proline, serine, threonine, tryptophan, valine, and the sphingolipid SM C26:1, and decreases in the glycerophospholipids, i.e., the arachidonic acid-containing phosphatidylcholine (PC aa) C30:2 and the PC aa C32:3. This study demonstrates that metabolic profiling is a useful approach to identify acute and tertiary effects in an excitotoxic lesion model, and generating a short list of targets with future potential in the hunt for identification, stratification, and possibly therapy. PMID: 28494460 [PubMed - as supplied by publisher]

Related Articles Metabolomics analysis: Finding out metabolic building blocks. PLoS One. 2017;12(5):e0177031 Authors: Alberich R, Castro JA, Llabrés M, Palmer-Rodríguez P Abstract In this paper we propose a new methodology for the analysis of metabolic networks. We use the notion of strongly connected components of a graph, called in this context metabolic building blocks. Every strongly connected component is contracted to a single node in such a way that the resulting graph is a directed acyclic graph, called a metabolic DAG, with a considerably reduced number of nodes. The property of being a directed acyclic graph brings out a background graph topology that reveals the connectivity of the metabolic network, as well as bridges, isolated nodes and cut nodes. Altogether, it becomes a key information for the discovery of functional metabolic relations. Our methodology has been applied to the glycolysis and the purine metabolic pathways for all organisms in the KEGG database, although it is general enough to work on any database. As expected, using the metabolic DAGs formalism, a considerable reduction on the size of the metabolic networks has been obtained, specially in the case of the purine pathway due to its relative larger size. As a proof of concept, from the information captured by a metabolic DAG and its corresponding metabolic building blocks, we obtain the core of the glycolysis pathway and the core of the purine metabolism pathway and detect some essential metabolic building blocks that reveal the key reactions in both pathways. Finally, the application of our methodology to the glycolysis pathway and the purine metabolism pathway reproduce the tree of life for the whole set of the organisms represented in the KEGG database which supports the utility of this research. PMID: 28493998 [PubMed - in process]

Related Articles shinyheatmap: Ultra fast low memory heatmap web interface for big data genomics. PLoS One. 2017;12(5):e0176334 Authors: Khomtchouk BB, Hennessy JR, Wahlestedt C Abstract BACKGROUND: Transcriptomics, metabolomics, metagenomics, and other various next-generation sequencing (-omics) fields are known for their production of large datasets, especially across single-cell sequencing studies. Visualizing such big data has posed technical challenges in biology, both in terms of available computational resources as well as programming acumen. Since heatmaps are used to depict high-dimensional numerical data as a colored grid of cells, efficiency and speed have often proven to be critical considerations in the process of successfully converting data into graphics. For example, rendering interactive heatmaps from large input datasets (e.g., 100k+ rows) has been computationally infeasible on both desktop computers and web browsers. In addition to memory requirements, programming skills and knowledge have frequently been barriers-to-entry for creating highly customizable heatmaps. RESULTS: We propose shinyheatmap: an advanced user-friendly heatmap software suite capable of efficiently creating highly customizable static and interactive biological heatmaps in a web browser. shinyheatmap is a low memory footprint program, making it particularly well-suited for the interactive visualization of extremely large datasets that cannot typically be computed in-memory due to size restrictions. Also, shinyheatmap features a built-in high performance web plug-in, fastheatmap, for rapidly plotting interactive heatmaps of datasets as large as 105-107 rows within seconds, effectively shattering previous performance benchmarks of heatmap rendering speed. CONCLUSIONS: shinyheatmap is hosted online as a freely available web server with an intuitive graphical user interface: http://shinyheatmap.com. The methods are implemented in R, and are available as part of the shinyheatmap project at: https://github.com/Bohdan-Khomtchouk/shinyheatmap. Users can access fastheatmap directly from within the shinyheatmap web interface, and all source code has been made publicly available on Github: https://github.com/Bohdan-Khomtchouk/fastheatmap. PMID: 28493881 [PubMed - in process]

Related Articles Comparative Metabolic Response between Cucumber (Cucumis sativus) and Corn (Zea Mays) to a Cu(OH)2 Nanopesticide. J Agric Food Chem. 2017 May 11;: Authors: Zhao L, Huang Y, Keller AA Abstract Due to their unique properties, copper-based nanopesticides are emerging in the market. Thus, understanding their effect on crop plants is very important. Metabolomics can capture a snapshot of cellular metabolic responses to a stressor. We selected maize and cucumber as model plants to expose to different doses of Cu(OH)2 nanopesticide. GC-TOF-MS based metabolomics was employed to determine the metabolic response of these two species. Results revealed significant differences in metabolite profile changes between maize and cucumber. Furthermore, the Cu(OH)2 nanopesticide induced metabolic reprogramming in both species, but in a different manner. In maize, several intermediates metabolite of the glycolysis pathway and tricarboxylic acid cycle (TCA) were up-regulated, indicating the energy metabolism was activated. In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense related pathway. In cucumber, arginine and proline metabolic pathways were the most significantly altered pathway. Both species exhibited altered levels of fatty acids and polysaccharides, suggesting the cell membrane and cell wall composition may change in response to Cu(OH)2 nanopesticide. Thus, metabolomics helps to deeply understand the differential response of these plants to the same nanopesticide stressor. PMID: 28493687 [PubMed - as supplied by publisher]

Related Articles Overlapping MALDI-Mass Spectrometry Imaging for In-Parallel MS and MS/MS Data Acquisition without Sacrificing Spatial Resolution. J Am Soc Mass Spectrom. 2017 May 10;: Authors: Hansen RL, Lee YJ Abstract Metabolomics experiments require chemical identifications, often through MS/MS analysis. In mass spectrometry imaging (MSI), this necessitates running several serial tissue sections or using a multiplex data acquisition method. We have previously developed a multiplex MSI method to obtain MS and MS/MS data in a single experiment to acquire more chemical information in less data acquisition time. In this method, each raster step is composed of several spiral steps and each spiral step is used for a separate scan event (e.g., MS or MS/MS). One main limitation of this method is the loss of spatial resolution as the number of spiral steps increases, limiting its applicability for high-spatial resolution MSI. In this work, we demonstrate multiplex MS imaging is possible without sacrificing spatial resolution by the use of overlapping spiral steps, instead of spatially separated spiral steps as used in the previous work. Significant amounts of matrix and analytes are still left after multiple spectral acquisitions, especially with nanoparticle matrices, so that high quality MS and MS/MS data can be obtained on virtually the same tissue spot. This method was then applied to visualize metabolites and acquire their MS/MS spectra in maize leaf cross-sections at 10 μm spatial resolution. Graphical Abstract ᅟ. PMID: 28493035 [PubMed - as supplied by publisher]

Related Articles Haploinsufficiency in the mitochondrial protein CHCHD4 reduces brain injury in a mouse model of neonatal hypoxia-ischemia. Cell Death Dis. 2017 May 11;8(5):e2781 Authors: Sun Y, Li T, Xie C, Xu Y, Zhou K, Rodriguez J, Han W, Wang X, Kroemer G, Modjtahedi N, Blomgren K, Zhu C Abstract Mitochondria contribute to neonatal hypoxic-ischemic brain injury by releasing potentially toxic proteins into the cytosol. CHCHD4 is a mitochondrial intermembrane space protein that plays a major role in the import of intermembrane proteins and physically interacts with apoptosis-inducing factor (AIF). The purpose of this study was to investigate the impact of CHCHD4 haploinsufficiency on mitochondrial function and brain injury after cerebral hypoxia-ischemia (HI) in neonatal mice. CHCHD4(+/-) and wild-type littermate mouse pups were subjected to unilateral cerebral HI on postnatal day 9. CHCHD4 haploinsufficiency reduced insult-related AIF and superoxide dismutase 2 release from the mitochondria and reduced neuronal cell death. The total brain injury volume was reduced by 21.5% at 3 days and by 31.3% at 4 weeks after HI in CHCHD4(+/-) mice. However, CHCHD4 haploinsufficiency had no influence on mitochondrial biogenesis, fusion, or fission; neural stem cell proliferation; or neural progenitor cell differentiation. There were no significant changes in the expression or distribution of p53 protein or p53 pathway-related genes under physiological conditions or after HI. These results suggest that CHCHD4 haploinsufficiency afforded persistent neuroprotection related to reduced release of mitochondrial intermembrane space proteins. The CHCHD4-dependent import pathway might thus be a potential therapeutic target for preventing or treating neonatal brain injury. PMID: 28492551 [PubMed - in process]

Related Articles Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations. Nutrients. 2017 May 11;9(5): Authors: Troisi J, Pierri L, Landolfi A, Marciano F, Bisogno A, Belmonte F, Palladino C, Nuzio SG, Campiglia P, Vajro P Abstract To get insight into still elusive pathomechanisms of pediatric obesity and non-alcoholic fatty liver disease (NAFLD) we explored the interplay among GC-MS studied urinary metabolomic signature, gut liver axis (GLA) abnormalities, and food preferences (Kid-Med). Intestinal permeability (IP), small intestinal bacterial overgrowth (SIBO), and homeostatic model assessment-insulin resistance were investigated in forty children (mean age 9.8 years) categorized as normal weight (NW) or obese (body mass index <85th or >95th percentile, respectively) ± ultrasonographic bright liver and hypertransaminasemia (NAFLD). SIBO was increased in all obese children (p = 0.0022), IP preferentially in those with NAFLD (p = 0.0002). The partial least-square discriminant analysis of urinary metabolome correctly allocated children based on their obesity, NAFLD, visceral fat, pathological IP and SIBO. Compared to NW, obese children had (1) higher levels of glucose/1-methylhistidine, the latter more markedly in NAFLD patients; and (2) lower levels of xylitol, phenyl acetic acid and hydroquinone, the latter especially in children without NAFLD. The metabolic pathways of BCAA and/or their metabolites correlated with excess of visceral fat centimeters (leucine/oxo-valerate), and more deranged IP and SIBO (valine metabolites). Urinary metabolome analysis contributes to define a metabolic fingerprint of pediatric obesity and related NAFLD, by identifying metabolic pathways/metabolites reflecting typical obesity dietary habits and GLA perturbations. PMID: 28492501 [PubMed - in process]

Related Articles Digitizing mass spectrometry data to explore the chemical diversity and distribution of marine cyanobacteria and algae. Elife. 2017 May 11;6: Authors: Luzzatto Knaan T, Garg N, Wang M, Glukhov E, Peng Y, Ackermann G, Amir A, Duggan BM, Ryazanov S, Gerwick L, Knight R, Alexandrov T, Bandeira N, Gerwick WH, Dorrestein PC Abstract Natural product screening programs have uncovered molecules from diverse natural sources with various biological activities and unique structures. However, much is yet underexplored and additional information is hidden in these exceptional collections. We applied untargeted mass spectrometry approaches to capture the chemical space and dispersal patterns of metabolites from an in-house library of marine cyanobacterial and algal collections. Remarkably, 86% of the metabolomics signals detected were not found in other available datasets of similar nature, supporting the hypothesis that marine cyanobacteria and algae possess distinctive metabolomes. The data were plotted onto a world map representing 8 major sampling sites, and revealed potential geographic locations with high chemical diversity. We demonstrate the use of these inventories as a tool to explore the diversity and distribution of natural products. Finally, we utilized this tool to guide the isolation of a new cyclic lipopeptide, yuvalamide A, from a marine cyanobacterium. PMID: 28492366 [PubMed - as supplied by publisher]

Related Articles METABOLOMICS APPROACH IN THE INVESTIGATION OF METABOLIC CHANGES IN OBESE MEN AFTER 24 WEEKS OF COMBINED TRAINING. J Proteome Res. 2017 May 11;: Authors: Duft RG, Castro A, Bonfante ILP, Brunelli DT, Chacon-Mikahil MPT, Cavaglieri CR Abstract Obesity is associated with comorbidities related to metabolic disorders, due to excess of adipose tissue. Physical exercise has a major role in the prevention of obesity. Combined training (CT), especially, has been shown to improve markers of health. In this study, we used 1H NMR-based metabolomics to investigate changes in the metabolism of obese men, after 24 weeks of CT. Twenty-two obese (Body Mass Index 31 ± 1.4 kg/m²), middle-aged men (48.2 ± 6.1 years) were randomly assigned to a control group (CG, n = 11) or CT group (n = 11). The CT was performed three times a week (resistance and aerobic training) for 24 weeks. Blood samples were collected before and after experimental period. There was an improvement in body composition and physical fitness indices after CT training. Multivariate PCA and PLS-DA models showed a distinct separation between groups. Twenty metabolites with importance for projection (VIP) higher > 1.0 were identified, and four classified as best discriminators (tyrosine, 2-oxoisocaproate, histidine, pyruvate). Some metabolites were correlated with strength, VO2peak, fat and lean body mass, waist circumference and insulin. In conclusion, 24 weeks of CT was effective for functional improvements and metabolic changes in obese middle-aged men. PMID: 28492082 [PubMed - as supplied by publisher]