PubMed

Related Articles Effects of Parental Temperature and Nitrate on Seed Performance are Reflected by Partly Overlapping Genetic and Metabolic Pathways. Plant Cell Physiol. 2016 Jan 6; Authors: He H, Willems L, Batushansky A, Fait A, Hanson J, Nijveen H, Hilhorst HW, Bentsink L Abstract Seed performance is affected by the seed maturation environment and previously, we have shown that temperature, nitrate and light intensity were the most influential environmental factors affecting seed performance. Seeds developed in these environments were selected to assess the underlying metabolic pathways, using a combination of transcriptomics and metabolomics. These analyses revealed that the effects of the temperature and nitrate parental environments were reflected by partly overlapping genetic and metabolic networks, as indicated by similar changes in metabolites and transcripts expression levels. Nitrogen-metabolism related metabolites (asparagine, GABA and allantoin) were significantly decreased in both low temperature (15°C) and low nitrate (N0) maturation environments. Correspondingly, nitrogen-metabolism genes (ALLANTOINASE, NITRATE REDUCTASE 1, NITRITE REDUCTASE 1 and NITRILASE 4) were differentially regulated in the low temperature and nitrate maturation environments, as compared with control conditions. High light intensity during seed maturation increased galactinol content, and displayed a high correlation with seed longevity. Low light had a genotype-specific effect on cell surface encoding genes in the DELAY OF GERMINATION 6-Near Isogenic Line (NILDOG6). Overall, the integration of phenotypes, metabolites and transcripts led to new insights in the regulation of seed performance. PMID: 26738545 [PubMed - as supplied by publisher]

Related Articles Proteomic and metabolomic analyses provide insight into production of volatile and non-volatile flavor components in mandarin hybrid fruit. BMC Plant Biol. 2015;15:76 Authors: Yu Q, Plotto A, Baldwin EA, Bai J, Huang M, Yu Y, Dhaliwal HS, Gmitter FG Abstract BACKGROUND: Although many of the volatile constituents of flavor and aroma in citrus have been identified, the knowledge of molecular mechanisms and regulation of volatile production are very limited. Our aim was to understand mechanisms of flavor volatile production and regulation in mandarin fruit. RESULT: Fruits of two mandarin hybrids, Temple and Murcott with contrasting volatile and non- volatile profiles, were collected at three developmental stages. A combination of methods, including the isobaric tags for relative and absolute quantification (iTRAQ), quantitative real-time polymerase chain reaction, gas chromatography, and high-performance liquid chromatography, was used to identify proteins, measure gene expression levels, volatiles, sugars, organic acids and carotenoids. Two thirds of differentially expressed proteins were identified in the pathways of glycolysis, citric acid cycle, amino acid, sugar and starch metabolism. An enzyme encoding valencene synthase gene (Cstps1) was more abundant in Temple than in Murcott. Valencene accounted for 9.4% of total volatile content in Temple, whereas no valencene was detected in Murcott fruit. Murcott expression of Cstps1 is severely reduced. CONCLUSION: We showed that the diversion of valencene and other sesquiterpenes into the terpenoid pathway together with high production of apocarotenoid volatiles might have resulted in the lower concentration of carotenoids in Temple fruit. PMID: 25848837 [PubMed - indexed for MEDLINE]

Related Articles Comparative metabolic and transcriptional analysis of a doubled diploid and its diploid citrus rootstock (C. junos cv. Ziyang xiangcheng) suggests its potential value for stress resistance improvement. BMC Plant Biol. 2015;15:89 Authors: Tan FQ, Tu H, Liang WJ, Long JM, Wu XM, Zhang HY, Guo WW Abstract BACKGROUND: Polyploidy has often been considered to confer plants a better adaptation to environmental stresses. Tetraploid citrus rootstocks are expected to have stronger stress tolerance than diploid. Plenty of doubled diploid citrus plants were exploited from diploid species for citrus rootstock improvement. However, limited metabolic and molecular information related to tetraploidization is currently available at a systemic biological level. This study aimed to evaluate the occurrence and extent of metabolic and transcriptional changes induced by tetraploidization in Ziyang xiangcheng (Citrus junos Sieb. ex Tanaka), which is a special citrus germplasm native to China and widely used as an iron deficiency tolerant citrus rootstock. RESULTS: Doubled diploid Ziyang xiangcheng has typical morphological and anatomical features such as shorter plant height, larger and thicker leaves, bigger stomata and lower stomatal density, compared to its diploid parent. GC-MS (Gas chromatography coupled to mass spectrometry) analysis revealed that tetraploidization has an activation effect on the accumulation of primary metabolites in leaves; many stress-related metabolites such as sucrose, proline and γ-aminobutyric acid (GABA) was remarkably up-regulated in doubled diploid. However, LC-QTOF-MS (Liquid chromatography quadrupole time-of-flight mass spectrometry) analysis demonstrated that tetraploidization has an inhibition effect on the accumulation of secondary metabolites in leaves; all the 33 flavones were down-regulated while all the 6 flavanones were up-regulated in 4x. By RNA-seq analysis, only 212 genes (0.8% of detected genes) are found significantly differentially expressed between 2x and 4x leaves. Notably, those genes were highly related to stress-response functions, including responses to salt stress, water and abscisic acid. Interestingly, the transcriptional divergence could not explain the metabolic changes, probably due to post-transcriptional regulation. CONCLUSION: Taken together, tetraploidization induced considerable changes in leaf primary and secondary metabolite accumulation in Ziyang xiangcheng. However, the effect of tetraploidization on transcriptome is limited. Compared to diploid, higher expression level of stress related genes and higher content of stress related metabolites in doubled diploid could be beneficial for its stress tolerance. PMID: 25848687 [PubMed - indexed for MEDLINE]

Related Articles Urinary metabonomics elucidate the therapeutic mechanism of Orthosiphon stamineus in mouse crystal-induced kidney injury. J Ethnopharmacol. 2015 May 26;166:323-32 Authors: Gao S, Chen W, Peng Z, Li N, Su L, Lv D, Li L, Lin Q, Dong X, Guo Z, Lou Z Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Orthosiphon stamineus (OS), a traditional Chinese herb, is often used for promoting urination and treating nephrolithiasis. AIM OF THE STUDY: Urolithiasis is a major worldwide public health burden due to its high incidence of recurrence and damage to renal function. However, the etiology for urolithiasis is not well understood. Metabonomics, the systematic study of small molecule metabolites present in biological samples, has become a valid and powerful tool for understanding disease phenotypes. In this study, a urinary metabolic profiling analysis was performed in a mouse model of renal calcium oxalate crystal deposition to identify potential biomarkers for crystal-induced renal damage and the anti-crystal mechanism of OS. MATERIALS AND METHODS: Thirty six mice were randomly divided into six groups including Saline, Crystal, Cystone and OS at dosages of 0.5g/kg, 1g/kg, and 2g/kg. A metabonomics approach using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was developed to perform the urinary metabolic profiling analysis. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were utilized to identify differences between the metabolic profiles of mice in the saline control group and crystal group. RESULTS: Using partial least squares-discriminant analysis, 30 metabolites were identified as potential biomarkers of crystal-induced renal damage. Most of them were primarily involved in amino acid metabolism, taurine and hypotaurine metabolism, purine metabolism, and the citrate cycle (TCA). After the treatment with OS, the levels of 20 biomarkers had returned to the levels of the control samples. CONCLUSIONS: Our results suggest that OS has a protective effect for mice with crystal-induced kidney injury via the regulation of multiple metabolic pathways primarily involving amino acid, energy and choline metabolism. PMID: 25794803 [PubMed - indexed for MEDLINE]

Related Articles Non-targeted metabolomic profile of Fagus sylvatica L. leaves using liquid chromatography with mass spectrometry and gas chromatography with mass spectrometry. Phytochem Anal. 2015 Mar-Apr;26(2):171-82 Authors: Cadahía E, Fernández de Simón B, Aranda I, Sanz M, Sánchez-Gómez D, Pinto E Abstract INTRODUCTION: Fagus sylvatica L. is one of the most widely distributed broad-leaved tree species in central and western Europe, important to the forest sector and an accurate biomarker of climate change. OBJECTIVE: To profile the beech leaf metabolome for future studies in order to investigate deeper into the characterisation of its metabolic response. METHODS: Leaf extracts were analysed using LC-MS by electrospray ionisation in negative mode from m/z 100-1700 and GC-MS by electron ionisation in scan mode from m/z 35-800. RESULTS: The LC-MS profile resulted in 56 compounds, of which 43 were identified and/or structurally characterised, including hydroxycinnamic acid derivatives, flavan-3-ols and proanthocyanidins, and flavonols. From a second analysis based on GC-MS, a total of 111 compounds were identified, including carbohydrates, polyalcohols, amino acids, organic acids, fatty acids, phenolic compounds, terpenoids, sterols and other related compounds. Many of the compounds identified were primary metabolites involved in major plant metabolic pathways, however, some secondary metabolites were also detected. Some of them play roles as tolerance-response osmoregulators and osmoprotectors in abiotic stress, or as anti-oxidants that reduce the effect of reactive oxygen species and promote many protective functions in plants. CONCLUSIONS: This study provides a broad and relevant insight into the metabolic status of F. sylvatica leaves, and serves as a base for future studies on physiological and molecular mechanisms involved in biotic or abiotic stress. PMID: 25516018 [PubMed - indexed for MEDLINE]

Metabolomic pathway visualization tool outsourcing editing function. Conf Proc IEEE Eng Med Biol Soc. 2015 Aug;2015:7659-7662 Authors: Sugimoto M Abstract Recent rapid improvements of measuring instrument enables us to perform various omics studies to simultaneous profile multiple molecules, which provides a holistic view of various molecular interactions, such as signal transaction, protein interactions, and metabolic pathways. Metabolomics is recently emerged omics that can identify and quantify low weight metabolites usually defined as organic molecules whose size is <; 1500 Da. In comparison to the other omics, the development of software tools to deal with metabolomic data is not matured. Conventional pathway drawing and visualization tool provide tool-specific unique functions, however, such user interface requires users to learn the usage and prevention for the use of these tools. Here, we developed a more generic pathway visualization tool. This tool incorporate pathway data yielded by common drawing tools, e.g. MS PowerPoint, and visualize the quantified values on the pathways. The statistical results also can be overlaid on each metabolite. The developed tools facilitate the interpreting metabolomic data in pathway forms. PMID: 26738066 [PubMed - as supplied by publisher]

The Swine Plasma Metabolome Chronicles "Many Days" Biological Timing and Functions Linked to Growth. PLoS One. 2016;11(1):e0145919 Authors: Bromage TG, Idaghdour Y, Lacruz RS, Crenshaw TD, Ovsiy O, Rotter B, Hoffmeier K, Schrenk F Abstract The paradigm of chronobiology is based almost wholly upon the daily biological clock, or circadian rhythm, which has been the focus of intense molecular, cellular, pharmacological, and behavioral, research. However, the circadian rhythm does not explain biological timings related to fundamental aspects of life history such as rates of tissue/organ/body size development and control of the timing of life stages such as gestation length, age at maturity, and lifespan. This suggests that another biological timing mechanism is at work. Here we focus on a "many days" (multidien) chronobiological period first observed as enigmatic recurring growth lines in developing mammalian tooth enamel that is strongly associate with all adult tissue, organ, and body masses as well as life history attributes such as gestation length, age at maturity, weaning, and lifespan, particularly among the well studied primates. Yet, knowledge of the biological factors regulating the patterning of mammalian life, such as the development of body size and life history structure, does not exist. To identify underlying molecular mechanisms we performed metabolome and genome analyses from blood plasma in domestic pigs. We show that blood plasma metabolites and small non-coding RNA (sncRNA) drawn from 33 domestic pigs over a two-week period strongly oscillate on a 5-day multidien rhythm, as does the pig enamel rhythm. Metabolomics and genomics pathway analyses actually reveal two 5-day rhythms, one related to growth in which biological functions include cell proliferation, apoptosis, and transcription regulation/protein synthesis, and another 5-day rhythm related to degradative pathways that follows three days later. Our results provide experimental confirmation of a 5-day multidien rhythm in the domestic pig linking the periodic growth of enamel with oscillations of the metabolome and genome. This association reveals a new class of chronobiological rhythm and a snapshot of the biological bases that regulate mammalian growth, body size, and life history. PMID: 26735517 [PubMed - as supplied by publisher]

Metabolomic profile in pancreatic cancer patients: a consensusbased approach to identify highly discriminating metabolites. Oncotarget. 2015 Dec 31; Authors: Di Gangi IM, Mazza T, Fontana A, Copetti M, Fusilli C, Ippolito A, Mattivi F, Latiano A, Andriulli A, Vrhovsek U, Pazienza V Abstract PURPOSE: pancreatic adenocarcinoma is the fourth leading cause of cancer related deaths due to its aggressive behavior and poor clinical outcome. There is a considerable variability in the frequency of serum tumor markers in cancer' patients. We performed a metabolomics screening in patients diagnosed with pancreatic cancer. EXPERIMENTAL DESIGN: Two targeted metabolomic assays were conducted on 40 serum samples of patients diagnosed with pancreatic cancer and 40 healthy controls. Multivariate methods and classification trees were performed. MATERIALS AND METHODS: Sparse partial least squares discriminant analysis (SPLS-DA) was used to reduce the high dimensionality of a pancreatic cancer metabolomic dataset, differentiating between pancreatic cancer (PC) patients and healthy subjects. Using Random Forest analysis palmitic acid, 1,2-dioleoyl-sn-glycero-3-phospho-rac-glycerollanosterol, lignoceric acid, 1-monooleoyl-rac-glycerol, cholesterol 5α,6α epoxide, erucic acid and taurolithocholic acid (T-LCA), oleoyl-L-carnitine, oleanolic acid were identified among 206 metabolites as highly discriminating between disease states. Comparison between Receiver Operating Characteristic (ROC) curves for palmitic acid and CA 19-9 showed that the area under the ROC curve (AUC) of palmitic acid (AUC=1.000; 95% confidence interval) is significantly higher than CA 19-9 (AUC=0.963; 95% confidence interval: 0.896-1.000). CONCLUSION: Mass spectrometry-based metabolomic profiling of sera from pancreatic cancer patients and normal subjects showed significant alterations in the profiles of the metabolome of PC patients as compared to controls. These findings offer an information-rich matrix for discovering novel candidate biomarkers with diagnostic or prognostic potentials. PMID: 26735340 [PubMed - as supplied by publisher]

A Bird's-Eye View of Molecular Changes in Plant Gravitropism Using Omics Techniques. Front Plant Sci. 2015;6:1176 Authors: Schüler O, Hemmersbach R, Böhmer M Abstract During evolution, plants have developed mechanisms to adapt to a variety of environmental stresses, including drought, high salinity, changes in carbon dioxide levels and pathogens. Central signaling hubs and pathways that are regulated in response to these stimuli have been identified. In contrast to these well studied environmental stimuli, changes in transcript, protein and metabolite levels in response to a gravitational stimulus are less well understood. Amyloplasts, localized in statocytes of the root tip, in mesophyll cells of coleoptiles and in the elongation zone of the growing internodes comprise statoliths in higher plants. Deviations of the statocytes with respect to the earthly gravity vector lead to a displacement of statoliths relative to the cell due to their inertia and thus to gravity perception. Downstream signaling events, including the conversion from the biophysical signal of sedimentation of distinct heavy mass to a biochemical signal, however, remain elusive. More recently, technical advances, including clinostats, drop towers, parabolic flights, satellites, and the International Space Station, allowed researchers to study the effect of altered gravity conditions - real and simulated micro- as well as hypergravity on plants. This allows for a unique opportunity to study plant responses to a purely anthropogenic stress for which no evolutionary program exists. Furthermore, the requirement for plants as food and oxygen sources during prolonged manned space explorations led to an increased interest in the identi-fication of genes involved in the adaptation of plants to microgravity. Transcriptomic, proteomic, phosphoproteomic, and metabolomic profiling strategies provide a sensitive high-throughput approach to identify biochemical alterations in response to changes with respect to the influence of the gravitational vector and thus the acting gravitational force on the transcript, protein and metabolite level. This review aims at summarizing recent experimental approaches and discusses major observations. PMID: 26734055 [PubMed]

Boosting Sensitivity in Liquid Chromatography-Fourier Transform Ion Cyclotron Resonance-Tandem Mass Spectrometry for Product Ion Analysis of Monoterpene Indole Alkaloids. Front Plant Sci. 2015;6:1127 Authors: Nakabayashi R, Tsugawa H, Kitajima M, Takayama H, Saito K Abstract In metabolomics, the analysis of product ions in tandem mass spectrometry (MS/MS) is noteworthy to chemically assign structural information. However, the development of relevant analytical methods are less advanced. Here, we developed a method to boost sensitivity in liquid chromatography-Fourier transform ion cyclotron resonance-tandem mass spectrometry analysis (MS/MS boost analysis). To verify the MS/MS boost analysis, both quercetin and uniformly labeled (13)C quercetin were analyzed, revealing that the origin of the product ions is not the instrument, but the analyzed compounds resulting in sensitive product ions. Next, we applied this method to the analysis of monoterpene indole alkaloids (MIAs). The comparative analyses of MIAs having indole basic skeleton (ajmalicine, catharanthine, hirsuteine, and hirsutine) and oxindole skeleton (formosanine, isoformosanine, pteropodine, isopteropodine, rhynchophylline, isorhynchophylline, and mitraphylline) identified 86 and 73 common monoisotopic ions, respectively. The comparative analyses of the three pairs of stereoisomers showed more than 170 common monoisotopic ions in each pair. This method was also applied to the targeted analysis of MIAs in Catharanthus roseus and Uncaria rhynchophylla to profile indole and oxindole compounds using the product ions. This analysis is suitable for chemically assigning features of the metabolite groups, which contributes to targeted metabolome analysis. PMID: 26734034 [PubMed]

Proteomics and Metabolomics: Two Emerging Areas for Legume Improvement. Front Plant Sci. 2015;6:1116 Authors: Ramalingam A, Kudapa H, Pazhamala LT, Weckwerth W, Varshney RK Abstract The crop legumes such as chickpea, common bean, cowpea, peanut, pigeonpea, soybean, etc. are important sources of nutrition and contribute to a significant amount of biological nitrogen fixation (>20 million tons of fixed nitrogen) in agriculture. However, the production of legumes is constrained due to abiotic and biotic stresses. It is therefore imperative to understand the molecular mechanisms of plant response to different stresses and identify key candidate genes regulating tolerance which can be deployed in breeding programs. The information obtained from transcriptomics has facilitated the identification of candidate genes for the given trait of interest and utilizing them in crop breeding programs to improve stress tolerance. However, the mechanisms of stress tolerance are complex due to the influence of multi-genes and post-transcriptional regulations. Furthermore, stress conditions greatly affect gene expression which in turn causes modifications in the composition of plant proteomes and metabolomes. Therefore, functional genomics involving various proteomics and metabolomics approaches have been obligatory for understanding plant stress tolerance. These approaches have also been found useful to unravel different pathways related to plant and seed development as well as symbiosis. Proteome and metabolome profiling using high-throughput based systems have been extensively applied in the model legume species, Medicago truncatula and Lotus japonicus, as well as in the model crop legume, soybean, to examine stress signaling pathways, cellular and developmental processes and nodule symbiosis. Moreover, the availability of protein reference maps as well as proteomics and metabolomics databases greatly support research and understanding of various biological processes in legumes. Protein-protein interaction techniques, particularly the yeast two-hybrid system have been advantageous for studying symbiosis and stress signaling in legumes. In this review, several studies on proteomics and metabolomics in model and crop legumes have been discussed. Additionally, applications of advanced proteomics and metabolomics approaches have also been included in this review for future applications in legume research. The integration of these "omics" approaches will greatly support the identification of accurate biomarkers in legume smart breeding programs. PMID: 26734026 [PubMed]

Network analysis of the metabolome and transcriptome reveals novel regulation of potato pigmentation. J Exp Bot. 2016 Jan 4; Authors: Cho K, Cho KS, Sohn HB, Ha IJ, Hong SY, Lee H, Kim YM, Nam MH Abstract To gain insights into the regulatory networks related to anthocyanin biosynthesis and identify key regulatory genes, we performed an integrated analysis of the transcriptome and metabolome in sprouts germinated from three colored potato cultivars: light-red Hongyoung, dark-purple Jayoung, and white Atlantic. We investigated transcriptional and metabolic changes using statistical analyses and gene-metabolite correlation networks. Transcript and metabolite profiles were generated through high-throughput RNA-sequencing data analysis and ultraperformance liquid chromatography quadrupole time-of-flight tandem mass spectrometry, respectively. The identification and quantification of changes in anthocyanin were performed using molecular formula-based mass accuracy and specific features of their MS(2) spectra. Correlation tests of anthocyanin contents and transcriptional changes showed 823 strong correlations (correlation coefficient, R (2)>0.9) between 22 compounds and 119 transcripts categorized into flavonoid metabolism, hormones, transcriptional regulation, and signaling. The connection network of anthocyanins and genes showed a regulatory system involved in the pigmentation of light-red Hongyoung and dark-purple Jayoung potatoes, suggesting that this systemic approach is powerful for investigations into novel genes that are potential targets for the breeding of new valuable potato cultivars. PMID: 26733692 [PubMed - as supplied by publisher]

A strategy for the targeted metabolomics analysis of 11 gut microbiota-host co-metabolites in rat serum, urine and feces by ultra performance liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2015 Dec 14; Authors: Hou W, Zhong D, Zhang P, Li Y, Lin M, Liu G, Yao M, Liao Q, Xie Z Abstract Microbiota-host co-metabolites are well-known to play important physiological roles, and their dysregulation has been found to be closely related to various diseases, including but not limited to inflammatory disorders. We developed herein an original and feasible method using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The method developed enables rapid quantification of 11 key gut microbiota-host co-metabolites spanning the succinate, phenylacetylglutamine, hippurate and trimethylamine metabolic pathways within 10min. With this method, we were able to simultaneously monitor inflammation-induced alterations of these metabolites in rat serum, urine and feces matrices. The measured levels for this panel of endogenous metabolites ranged from 0.001 to 172.8μgmL(-1). The intra- and inter-day precision of three analytes was less than 13.1% and the accuracy was between -13.0 to 11.2% for all QC levels. The extraction recoveries in serum ranged from 85.4 to 103.2%, while the RSD was 9.0% or less for all recoveries. In addition, extraction recoveries of 11 analytes in urine and feces samples were between 85.7% and 102.0% and RSD was less than 9.5%. The method developed here has been successfully applied to the analysis of real samples from 2,4,6-trinitrobenzenesulfonic acid-induced Crohn's disease in rats. All of these results suggest that the presently developed method is sufficiently sensitive and robust to simultaneously monitor co-metabolites with diverse properties and a range of different concentrations. Therefore, this method will be expected to be useful for comprehensive studies of the pathophysiological roles and mechanisms of these key microbiota-host co-metabolites, which reflect the function of the intestine, consequently offering novel opportunities for evaluating the occurrence, development and therapeutic effects of diseases related to microbiota disturbances. PMID: 26733392 [PubMed - as supplied by publisher]

A GC-MS urinary quantitative metabolomics analysis in depressed patients treated with TCM formula of Xiaoyaosan. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Dec 18; Authors: Tian JS, Peng GJ, Wu YF, Zhou JJ, Xiang H, Gao XX, Zhou YZ, Qin XM, Du GH Abstract Xiaoyaosan, one of the best-known traditional Chinese medicine prescriptions, has been widely used in China for the treatment of mental disorders such as depression. Although both clinical application and animal experiments indicate that Xiaoyaosan has an obvious antidepressant effect, the mechanism still remains unclarified, and there are few studies quantitatively measured the biomarkers of Xiaoyaosan treatment by metabolomics to determination. In this study, 25 depressed patients and 33 healthy volunteers were recruited. A GC-MS based metabolomics approach and the multivariate statistical methods were used for analyzing the urine metabolites of depressed patients before and after treatment compared with healthy controls. Then the biomakers through metabolomics determination were carried out the quantitative analysis. In total, 5 metabolites were identified as the potential diseased and therapeutic biomarkers of depression and Xiaoyaosan. Alanine, citrate and hippurate levels were significantly increased in the urine samples from depressed patients compared with healthy controls, while phenylalanie and tyrosine levels were significantly decreased. However, after Xiaoyaosan treatment for 6 weeks, phenylalanie and tyrosine levels were significantly increased (p<0.05) and alanine, citrate and hippurate levels significantly decreased (p<0.05). Xiaoyaosan has a good priority on the treatment of depression and the ability to adjust the neurotransmitters to obtain the best treated response and also could regulate the metabolism of amino acids and promote to produce energy meet the needs of the body. PMID: 26733091 [PubMed - as supplied by publisher]

Identification of Proteins Bound to Dengue Viral RNA In Vivo Reveals New Host Proteins Important for Virus Replication. MBio. 2016;7(1) Authors: Phillips SL, Soderblom EJ, Bradrick SS, Garcia-Blanco MA Abstract UNLABELLED: Dengue virus is the most prevalent cause of arthropod-borne infection worldwide. Due to the limited coding capacity of the viral genome and the complexity of the viral life cycle, host cell proteins play essential roles throughout the course of viral infection. Host RNA-binding proteins mediate various aspects of virus replication through their physical interactions with viral RNA. Here we describe a technique designed to identify such interactions in the context of infected cells using UV cross-linking followed by antisense-mediated affinity purification and mass spectrometry. Using this approach, we identified interactions, several of them novel, between host proteins and dengue viral RNA in infected Huh7 cells. Most of these interactions were subsequently validated using RNA immunoprecipitation. Using small interfering RNA (siRNA)-mediated gene silencing, we showed that more than half of these host proteins are likely involved in regulating virus replication, demonstrating the utility of this method in identifying biologically relevant interactions that may not be identified using traditional in vitro approaches. IMPORTANCE: Dengue virus is the most prevalent cause of arthropod-borne infection worldwide. Viral RNA molecules physically interact with cellular RNA-binding proteins (RBPs) throughout the course of infection; the identification of such interactions will lead to the elucidation of the molecular mechanisms of virus replication. Until now, the identification of host proteins bound to dengue viral RNA has been accomplished using in vitro strategies. Here, we used a method for the specific purification of dengue viral ribonucleoprotein (RNP) complexes from infected cells and subsequently identified the associated proteins by mass spectrometry. We then validated a functional role for the majority of these proteins in mediating efficient virus replication. This approach has broad relevance to virology and RNA biology, as it could theoretically be used to purify any viral RNP complex of interest. PMID: 26733069 [PubMed - in process]

Changes in the metabolome of rats after exposure to arginine and N-carbamylglutamate in combination with diquat, a compound that causes oxidative stress, assessed by (1)H NMR spectroscopy. Food Funct. 2016 Jan 6; Authors: Liu G, Xiao L, Cao W, Fang T, Jia G, Chen X, Zhao H, Wu C, Wang J Abstract Numerous factors can induce oxidative stress in animal production and lead to growth retardation, disease, and even death. Arginine and N-carbamylglutamate can alleviate the effects of oxidative stress. However, the systematic changes in metabolic biochemistry linked to oxidative stress and arginine and N-carbamylglutamate treatment remain largely unknown. This study aims to examine the effects of arginine and N-carbamylglutamate on rat metabolism under oxidative stress. Thirty rats were randomly divided into three dietary groups (n = 10 each). The rats were fed a basal diet supplemented with 0 (control), 1% arginine, or 0.1% N-carbamylglutamate for 30 days. On day 28, the rats in each treatment were intraperitoneally injected with diquat at 12 mg per kg body weight or sterile solution. Urine and plasma samples were analyzed by metabolomics. Compared with the diquat group, the arginine + diquat group had significantly lower levels of acetamide, alanine, lysine, pyruvate, tyrosine, α-glucose, and β-glucose in plasma; N-carbamylglutamate + diquat had higher levels of 3-hydroxybutyrate, 3-methylhistidine, acetone, allantoin, asparagine, citrate, phenylalanine, trimethylamine-N-oxide, and tyrosine, and lower levels of low density lipoprotein, lipid, lysine, threonine, unsaturated lipid, urea, and very low density lipoprotein (P < 0.05) in plasma. Compared with the diquat group, the arginine + diquat group had significantly higher levels of citrate, creatinine, homogentisate, and α-ketoglutarate while lower levels of acetamide, citrulline, ethanol, glycine, isobutyrate, lactate, malonate, methymalonate, N-acetylglutamate, N-methylnicotinamide, propionate, and β-glucose (P < 0.05) in urine. Compared with the diquat group, the N-carbamylglutamate + diquat group had significantly higher levels of allantoin, citrate, homogentisate, phenylacetylglycine, α-ketoglutarate, and β-glucose while lower levels of acetamide, acetate, acetone, benzoate, citrulline, ethanol, hippurate, lactate, N-acetylglutamate, nicotinamide, ornithine, and trigonelline (P < 0.05) in urine. Overall, these results suggest that arginine and N-carbamylglutamate can alter the metabolome associated with energy metabolism, amino acid metabolism, and gut microbiota metabolism under oxidative stress. PMID: 26732548 [PubMed - as supplied by publisher]

(1)H-Nuclear Magnetic Resonance-Based Plasma Metabolic Profiling of Dairy Cows with Fatty Liver. Asian-Australas J Anim Sci. 2016 Feb;29(2):219-29 Authors: Xu C, Sun LW, Xia C, Zhang HY, Zheng JS, Wang JS Abstract Fatty liver is a common metabolic disorder of dairy cows during the transition period. Historically, the diagnosis of fatty liver has involved liver biopsy, biochemical or histological examination of liver specimens, and ultrasonographic imaging of the liver. However, more convenient and noninvasive methods would be beneficial for the diagnosis of fatty liver in dairy cows. The plasma metabolic profiles of dairy cows with fatty liver and normal (control) cows were investigated to identify new biomarkers using (1)H nuclear magnetic resonance. Compared with the control group, the primary differences in the fatty liver group included increases in β-hydroxybutyric acid, acetone, glycine, valine, trimethylamine-N-oxide, citrulline, and isobutyrate, and decreases in alanine, asparagine, glucose, γ-aminobutyric acid glycerol, and creatinine. This analysis revealed a global profile of endogenous metabolites, which may present potential biomarkers for the diagnosis of fatty liver in dairy cows. PMID: 26732447 [PubMed]

Related Articles Mechanisms of allergic disease - environmental and genetic determinants for the development of allergy. Clin Exp Allergy. 2015 May;45(5):844-58 Authors: Campbell DE, Boyle RJ, Thornton CA, Prescott SL Abstract Allergic disease can be viewed as an early manifestation of immune dysregulation. Environmental exposures including maternal inflammation, diet, nutrient balance, microbial colonization and toxin exposures can directly and indirectly influence immune programming in both pregnancy and the postnatal period. The intrauterine microclimate is critical for maternal and fetal immunological tolerance to sustain viable pregnancy, but appears susceptible to environmental conditions. Targeting aspects of the modern environment that promote aberrant patterns of immune response is logical for interventions aimed at primary prevention of allergic disease. Defining the mechanisms that underpin both natural and therapeutic acquisition of immunological tolerance in childhood will provide insights into the drivers of persistent immune dysregulation. In this review, we summarize evidence that allergy is a consequence of intrauterine and early life immune dysregulation, with specific focus on contributing environmental risk factors occurring preconception, in utero and in the early postnatal period. We explore the immunological mechanisms which underpin tolerance and persistence of allergic disease during childhood. It is likely that future investigations within these two domains will ultimately provide a road map for the primary prevention of allergic disease. PMID: 25772780 [PubMed - indexed for MEDLINE]

Related Articles Detection of new human metabolic urinary markers in chronic alcoholism and their reversal by aqueous extract of Tinospora cordifolia stem. Alcohol Alcohol. 2015 May;50(3):271-81 Authors: Mittal A, Dabur R Abstract AIMS: We have studied urine metabolic signature of chronic alcoholism (CA) before and after treatment with an Ayurvedic drug Tinospora cordifolia aqueous extract (TCE). METHODS: Urinary metabolites of chronic alcoholics and apparently healthy subjects were profiled using HPLC-Q-TOF-MS. Discrimination models from the initial data sets were able to correctly assign the unknown samples to the CA, treated or healthy groups in validation sets with r(2) > 0.98. RESULTS: Metabolic signature in CA patients include changed tryptophan, fatty acids and pyrimidines metabolism. Several novel biomarkers of alcoholism were observed in urine for the first time which includes, 5-hydroxyindole, phenylacetic acid, picolinic acid, quinaldic acid, histidine, cystathionine, riboflavin, tetrahydrobiopterin and chenodeoxyglycocholic acid, in addition to previously reported biomarkers. Treatment of CA with TCE reverted the levels of most of the biomarkers except tetrahydrobiopterin levels. CONCLUSIONS: These results suggested that the measurement of these urine metabolites could be used as a non-invasive diagnostic method for the detection of CA. As TCE treatment significantly reversed the affected pathways without any side effect. Overall, the present data depicts that TCE may be used either alone or adjunct in reducing alcohol-induced disorders. PMID: 25754126 [PubMed - indexed for MEDLINE]

Reply: Metabolomics and Mycobacterial Disease: Don't Forget the Bioinformatics. Ann Am Thorac Soc. 2016 Jan;13(1):142-143 Authors: Mirsaeidi M, Banoei MM, Winston BW, Schraufnagel DE PMID: 26730873 [PubMed - as supplied by publisher]