Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Metabolic profiling of chickpea-Fusarium interaction identifies differential modulation of disease resistance pathways.

Tue, 05/05/2015 - 17:37
Metabolic profiling of chickpea-Fusarium interaction identifies differential modulation of disease resistance pathways. Phytochemistry. 2015 Apr 29; Authors: Kumar Y, Dholakia BB, Panigrahi P, Kadoo NY, Giri AP, Gupta VS Abstract Chickpea is the third most widely grown legume in the world and mainly used as a vegetarian source of human dietary protein. Fusarium wilt, caused by Fusarium oxysporum f. sp. ciceri (Foc), is one of the major threats to global chickpea production. Host resistance is the best way to protect crops from diseases; however, in spite of using various approaches, the mechanism of Foc resistance in chickpea remains largely obscure. In the present study, non-targeted metabolic profiling at several time points of resistant and susceptible chickpea cultivars using high-resolution liquid chromatography-mass spectrometry was applied to better understand the mechanistic basis of wilt resistance or susceptibility. Multivariate analysis of the data (OPLS-DA) revealed discriminating metabolites in chickpea root tissue after Foc inoculation such as flavonoids, isoflavonoids, alkaloids, amino acids and sugars. Foc inoculated resistant plants had more flavonoids and isoflavonoids along with their malonyl conjugates. Many antifungal metabolites that were induced after Foc infection viz., aurantion-obstine β-glucosides and querecitin were elevated in resistant cultivar. Overall, diverse genetic and biochemical mechanisms were operational in the resistant cultivar for Foc defense as compared to the susceptible plant. The resistant chickpea plants employed the above-mentioned metabolic pathways as potential defense strategy against Foc. PMID: 25935544 [PubMed - as supplied by publisher]

Day-3 embryo metabolomics in the spent culture media is altered in obese women undergoing in vitro fertilization.

Tue, 05/05/2015 - 17:37
Day-3 embryo metabolomics in the spent culture media is altered in obese women undergoing in vitro fertilization. Fertil Steril. 2015 Apr 29; Authors: Bellver J, De Los Santos MJ, Alamá P, Castelló D, Privitera L, Galliano D, Labarta E, Vidal C, Pellicer A, Domínguez F Abstract OBJECTIVE: To determine whether the global metabolomic profile of the spent culture media (SCM) of day-3 embryos is different in obese and normoweight women undergoing in vitro fertilization (IVF). DESIGN: Prospective cohort analysis. SETTING: IVF clinic. PATIENT(S): Twenty-eight young, nonsmoking women with normoweight, nonsmoking male partners with mild/normal sperm factors undergoing a first IVF attempt for idiopathic infertility, tubal factor infertility, or failed ovulation induction: obese ovulatory women (n = 12); obese women with polycystic ovary syndrome (PCOS; n = 4); normoweight ovulatory women (n = 12). INTERVENTION(S): Fifty μl of SCM collected from two day-3 embryos of each cohort. MAIN OUTCOME MEASURE(S): Metabolomic profiling via ultrahigh performance liquid chromatography coupled to mass spectrometry of SCM from a total of 56 embryos. RESULT(S): The untargeted metabolomic profile was different in obese and normoweight women. Partial least squares discriminant analysis resulted in a clear separation of samples when a total of 551 differential metabolites were considered. A prediction model was generated using the most consistent metabolites. Most of the metabolites identified were saturated fatty acids, which were detected in lower concentrations in the SCM of embryos from obese women. The metabolomic profile was similar in obese women with or without PCOS. CONCLUSION(S): The metabolomic profile in the SCM of day-3 embryos is different in normoweight and obese women. Saturated fatty acids seem to be reduced when embryos from obese patients are present. CLINICAL TRIAL REGISTRATION NUMBER: NCT01448863. PMID: 25935493 [PubMed - as supplied by publisher]

Perinatal protein restriction affects milk free amino acid and fatty acid profile in lactating rats: potential role on pup growth and metabolic status.

Tue, 05/05/2015 - 17:37
Perinatal protein restriction affects milk free amino acid and fatty acid profile in lactating rats: potential role on pup growth and metabolic status. J Nutr Biochem. 2015 Apr 13; Authors: Martin Agnoux A, Antignac JP, Boquien CY, David A, Desnots E, Ferchaud-Roucher V, Darmaun D, Parnet P, Alexandre-Gouabau MC Abstract Perinatal undernutrition affects not only fetal and neonatal growth but also adult health outcome, as suggested by the metabolic imprinting concept. Although maternal milk is the only channel through which nutrients are transferred from mother to offspring during the postnatal period, the impact of maternal undernutrition on milk composition is poorly understood. The present study investigates, in a rat model of nutritional programming, the effects of feeding an isocaloric, low-protein diet throughout gestation and lactation on milk composition and its possible consequences on offspring's growth and metabolic status. We used an integrated methodological approach that combined targeted analyses of macronutrients, free amino acid and fatty acid content throughout lactation, with an untargeted mass-spectrometric-based metabolomic phenotyping. Whereas perinatal dietary protein restriction failed to alter milk protein content, it dramatically decreased the concentration of most free amino acids at the end of lactation. Interestingly, a decrease of several amino acids involved in insulin secretion or gluconeogenesis was observed, suggesting that maternal protein restriction during the perinatal period may impact the insulinotrophic effect of milk, which may, in turn, account for the slower growth of the suckled male offspring. Besides, the decrease in sulfur amino acids may alter redox status in the offspring. Maternal undernutrition was also associated with an increase in milk total fatty acid content, with modifications in their pattern. Altogether, our results show that milk composition is clearly influenced by maternal diet and suggest that alterations in milk composition may play a role in offspring growth and metabolic programming. PMID: 25935308 [PubMed - as supplied by publisher]

The Mouse Brain Metabolome: Region-Specific Signatures and Response to Excitotoxic Neuronal Injury.

Mon, 04/05/2015 - 11:44
Related Articles The Mouse Brain Metabolome: Region-Specific Signatures and Response to Excitotoxic Neuronal Injury. Am J Pathol. 2015 Apr 24; Authors: Jaeger C, Glaab E, Michelucci A, Binz TM, Koeglsberger S, Garcia P, Trezzi JP, Ghelfi J, Balling R, Buttini M Abstract Neurodegeneration is a multistep process characterized by a multitude of molecular entities and their interactions. Systems' analyses, or omics approaches, have become an important tool in characterizing this process. Although RNA and protein profiling made their entry into this field a couple of decades ago, metabolite profiling is a more recent addition. The metabolome represents a large part or all metabolites in a tissue, and gives a snapshot of its physiology. By using gas chromatography coupled to mass spectrometry, we analyzed the metabolic profile of brain regions of the mouse, and found that each region is characterized by its own metabolic signature. We then analyzed the metabolic profile of the mouse brain after excitotoxic injury, a mechanism of neurodegeneration implicated in numerous neurological diseases. More important, we validated our findings by measuring, histologically and molecularly, actual neurodegeneration and glial response. We found that a specific global metabolic signature, best revealed by machine learning algorithms, rather than individual metabolites, was the most robust correlate of neuronal injury and the accompanying gliosis, and this signature could serve as a global biomarker for neurodegeneration. We also observed that brain lesioning induced several metabolites with neuroprotective properties. Our results deepen the understanding of metabolic changes accompanying neurodegeneration in disease models, and could help rapidly evaluate these changes in preclinical drug studies. PMID: 25934215 [PubMed - as supplied by publisher]

Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research.

Mon, 04/05/2015 - 11:44
Related Articles Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research. Mol Neurobiol. 2015 May 2; Authors: Maes M, Nowak G, Caso JR, Leza JC, Song C, Kubera M, Klein H, Galecki P, Noto C, Glaab E, Balling R, Berk M Abstract Meta-analyses confirm that depression is accompanied by signs of inflammation including increased levels of acute phase proteins, e.g., C-reactive protein, and pro-inflammatory cytokines, e.g., interleukin-6. Supporting the translational significance of this, a meta-analysis showed that anti-inflammatory drugs may have antidepressant effects. Here, we argue that inflammation and depression research needs to get onto a new track. Firstly, the choice of inflammatory biomarkers in depression research was often too selective and did not consider the broader pathways. Secondly, although mild inflammatory responses are present in depression, other immune-related pathways cannot be disregarded as new drug targets, e.g., activation of cell-mediated immunity, oxidative and nitrosative stress (O&NS) pathways, autoimmune responses, bacterial translocation, and activation of the toll-like receptor and neuroprogressive pathways. Thirdly, anti-inflammatory treatments are sometimes used without full understanding of their effects on the broader pathways underpinning depression. Since many of the activated immune-inflammatory pathways in depression actually confer protection against an overzealous inflammatory response, targeting these pathways may result in unpredictable and unwanted results. Furthermore, this paper discusses the required improvements in research strategy, i.e., path and drug discovery processes, omics-based techniques, and systems biomedicine methodologies. Firstly, novel methods should be employed to examine the intracellular networks that control and modulate the immune, O&NS and neuroprogressive pathways using omics-based assays, including genomics, transcriptomics, proteomics, metabolomics, epigenomics, immunoproteomics and metagenomics. Secondly, systems biomedicine analyses are essential to unravel the complex interactions between these cellular networks, pathways, and the multifactorial trigger factors and to delineate new drug targets in the cellular networks or pathways. Drug discovery processes should delineate new drugs targeting the intracellular networks and immune-related pathways. PMID: 25934103 [PubMed - as supplied by publisher]

Multiwalled Carbon Nanotubes Dispersion Methods Affect Their Aggregation, Deposition, and Biomarker Response.

Thu, 30/04/2015 - 14:15
Multiwalled Carbon Nanotubes Dispersion Methods Affect Their Aggregation, Deposition, and Biomarker Response. Environ Sci Technol. 2015 Apr 29; Authors: Chang X, Henderson WM, Bouchard DC Abstract To systematically evaluate how dispersion methods affect multi-walled carbon nanotubes (MWNTs) environmental behaviors, MWNTs were dispersed in various solutions [e.g., surfactants, natural organic matter (NOM), and etc.] via ultrasonication (SON) and long-term stirring (LT). The two tested surfactants [anionic sodium dodecyl sulfate (SDS) and nonionic poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) (PEO-PPO-PEO) triblock copolymers (Pluronic)] could only disperse MWNTs via ultrasonication; while stable aqueous SON/MWNT and LT/MWNTs suspensions were formed in the presence of the two model NOMs [Suwannee river humic acid (SRHA) and fulvic acid (SRFA)]. Due to the inherent stochastic nature for both methods, the formed MWNTs suspensions were highly heterogeneous. Their physicochemical properties, including surface charge, size, and morphology, greatly depended upon the dispersant type and concentration but were not very sensitive to the preparation methods. Homo-aggregation and hetero-aggregation behaviors of the dispersed MWNTs were controlled by van der Waal and electrostatic forces, as well as other non-DLVO forces (e.g., steric, hydrophobic forces, etc.). Unlike the preparation method-independent physicochemical properties, LT/NOM-MWNTs and SON/NOM-MWNTs differed in their fathead minnow epithelial cell metabolomics profiles. PMID: 25924000 [PubMed - as supplied by publisher]

Distinct serum metabolomics profiles associated with malignant progression in the KrasG12D mouse model of pancreatic ductal adenocarcinoma.

Thu, 30/04/2015 - 14:15
Distinct serum metabolomics profiles associated with malignant progression in the KrasG12D mouse model of pancreatic ductal adenocarcinoma. BMC Genomics. 2015 Jan 15;16(Suppl 1):S1 Authors: LaConti JJ, Laiakis EC, Mays A, Peran I, Kim S, Shay JW, Riegel AT, Fornace AJ, Wellstein A Abstract BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths worldwide with less than a 6% 5-year survival rate. PDAC is associated with poor prognosis based on the late stage diagnosis of the disease. Current diagnostic tests lack the sensitivity and specificity to identify markers of early staging. Metabolomics has provided biomarkers for various diseases, stressors, and environmental exposures. In this study we utilized the p48-Cre/LSL-KrasG12D mouse model with age-matched wild type mice. This model shows malignant progression to PDAC analogous to the human disease stages via early and late pancreatic intra-epithelial neoplasia (PanIN) lesions. RESULTS: Serum was collected from mice with early PanIN lesions (at 3-5 months) and with late PanIN or invasive PDAC lesions (13-16 months), as determined by histopathology. Metabolomics analysis of the serum samples was conducted through UPLC-TOFMS (Ultra Performance Liquid Chromatography coupled to Time-of-flight Mass Spectrometry). Multivariate data analysis revealed distinct metabolic patterns in serum samples collected during malignant progression towards invasive PDAC. Animals with early or late stage lesions were distinguished from their respective controls with 82.1% and 81.5% accuracy, respectively. This also held up for randomly selected subgroups in the late stage lesion group that showed less variability between animals. One of the metabolites, citrate, was validated through tandem mass spectrometry and showed increased levels in serum with disease progression. Furthermore, serum metabolite signatures from animals with early stage lesions identified controls and animals with late stage lesions with 81.5% accuracy (p<0.01) and vice-versa with 73.2% accuracy (p<0.01). CONCLUSIONS: We conclude that metabolomics analysis of serum samples can identify the presence of early and late stage pancreatic cancer. PMID: 25923219 [PubMed - as supplied by publisher]

Top-down Targeted Metabolomics Reveals a Sulfur-Containing Metabolite with Inhibitory Activity against Angiotensin-Converting Enzyme in Asparagus officinalis.

Thu, 30/04/2015 - 14:15
Top-down Targeted Metabolomics Reveals a Sulfur-Containing Metabolite with Inhibitory Activity against Angiotensin-Converting Enzyme in Asparagus officinalis. J Nat Prod. 2015 Apr 29; Authors: Nakabayashi R, Yang Z, Nishizawa T, Mori T, Saito K Abstract The discovery of bioactive natural compounds containing sulfur, which is crucial for inhibitory activity against angiotensin-converting enzyme (ACE), is a challenging task in metabolomics. Herein, a new S-containing metabolite, asparaptine (1), was discovered in the spears of Asparagus officinalis by targeted metabolomics using mass spectrometry for S-containing metabolites. The contribution ratio (2.2%) to the IC50 value in the crude extract showed that asparaptine (1) is a new ACE inhibitor. PMID: 25922884 [PubMed - as supplied by publisher]

Paucimannosidic glycoepitopes are functionally involved in proliferation of neural progenitor cells in the subventricular zone.

Thu, 30/04/2015 - 14:15
Paucimannosidic glycoepitopes are functionally involved in proliferation of neural progenitor cells in the subventricular zone. Glycobiology. 2015 Apr 28; Authors: Dahmen AC, Fergen MT, Laurini C, Schmitz B, Loke I, Thaysen-Andersen M, Diestel S Abstract Protein glycosylation has received much attention due to its multiple functional roles in physiological and pathophysiological conditions. Paucimannose is a common mannosidic N-glycoepitope in invertebrates and plants but has only recently been detected in vertebrates. Herein, we demonstrate the presence of paucimannosidic epitopes specifically in early postnatal neural progenitor cells between postnatal day 0 and 7 in mouse brain suggesting a possible role in the development of neural progenitor cells. Paucimannosidic epitopes were also detected in human glioblastoma cells and human macrophages by immunofluorescence and mass spectrometric analysis. Its expression was significantly increased after proliferation arrest indicating its importance in regulation of cell proliferation. This hypothesis was further strengthened by reduced cell proliferation after application of paucimannose-reactive Mannitou antibody into culture medium of growing cells. Most interestingly, this reduction of cell proliferation upon administration of Mannitou antibody could also be observed in vivo in the subventricular zone of early postnatal mouse brain. Taken together, these observations demonstrate that paucimannosylation directly influences cell proliferation in various vertebrate cell types including early postnatal neural stem cells. PMID: 25922361 [PubMed - as supplied by publisher]

Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome.

Thu, 30/04/2015 - 14:15
Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome. J Physiol. 2015 Apr 29; Authors: Pereira TJ, Fonseca MA, Campbell KE, Moyce BL, Cole LK, Hatch GM, Doucette CA, Klein J, Aliani M, Dolinsky VW Abstract Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague-Dawley rats were fed a high-fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low-fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinemia and hyperglycemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor-α mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring. This article is protected by copyright. All rights reserved. PMID: 25922055 [PubMed - as supplied by publisher]

The 'prime-ome': towards a holistic approach to priming.

Thu, 30/04/2015 - 14:15
The 'prime-ome': towards a holistic approach to priming. Trends Plant Sci. 2015 Apr 25; Authors: Balmer A, Pastor V, Gamir J, Flors V, Mauch-Mani B Abstract Plants can be primed to respond faster and more strongly to stress and multiple pathways, specific for the encountered challenge, are involved in priming. This adaptability of priming makes it difficult to pinpoint an exact mechanism: the same phenotypic observation might be the consequence of unrelated underlying events. Recently, details of the molecular aspects of establishing a primed state and its transfer to offspring have come to light. Advances in techniques for detection and quantification of elements spanning the fields of transcriptomics, proteomics, and metabolomics, together with adequate bioinformatics tools, will soon allow us to take a holistic approach to plant defence. This review highlights the state of the art of new strategies to study defence priming in plants and provides perspectives towards 'prime-omics'. PMID: 25921921 [PubMed - as supplied by publisher]

Dynamic phosphoproteomics reveals TORC1-dependent regulation of yeast nucleotide and amino acid biosynthesis.

Thu, 30/04/2015 - 14:15
Dynamic phosphoproteomics reveals TORC1-dependent regulation of yeast nucleotide and amino acid biosynthesis. Sci Signal. 2015;8(374):rs4 Authors: Oliveira AP, Ludwig C, Zampieri M, Weisser H, Aebersold R, Sauer U Abstract Phosphoproteomics studies have unraveled the extent of protein phosphorylation as a key cellular regulation mechanism, but assigning functionality to specific phosphorylation events remains a major challenge. TORC1 (target of rapamycin complex 1) is a kinase-containing protein complex that transduces changes in nutrient availability into phosphorylation signaling events that alter cell growth and proliferation. To resolve the temporal sequence of phosphorylation responses to nutritionally and chemically induced changes in TORC1 signaling and to identify previously unknown kinase-substrate relationships in Saccharomyces cerevisiae, we performed quantitative mass spectrometry-based phosphoproteomic analyses after shifts in nitrogen sources and rapamycin treatment. From early phosphorylation events that were consistent over at least two experimental perturbations, we identified 51 candidate and 10 known proximal targets of TORC1 that were direct substrates of TORC1 or of one of its kinase or phosphatase substrates. By correlating these phosphoproteomics data with dynamic metabolomics data, we inferred the functional role of phosphorylation on the metabolic activity of 12 enzymes, including three candidate TORC1-proximal targets: Amd1, which is involved in nucleotide metabolism; Hom3, which is involved in amino acid metabolism; and Tsl1, which mediates carbohydrate storage. Finally, we identified the TORC1 substrates Sch9 and Atg1 as candidate kinases that phosphorylate Amd1 and Hom3, respectively. PMID: 25921291 [PubMed - in process]

Deoxycytidine-kinase (dCK) knock-down as a novel myeloprotective strategy in the context of fludarabine, cytarabine, or cladribine therapy.

Thu, 30/04/2015 - 14:15
Deoxycytidine-kinase (dCK) knock-down as a novel myeloprotective strategy in the context of fludarabine, cytarabine, or cladribine therapy. Leukemia. 2015 Apr 29; Authors: Lachmann N, Czarnecki K, Brennig S, Phaltane R, Heise M, Heinz N, Kempf H, Dilloo D, Kaever V, Schambach A, Heuser M, Moritz T PMID: 25921248 [PubMed - as supplied by publisher]

Technical brief funrich: An open access standalone functional enrichment and interaction network analysis tool.

Thu, 30/04/2015 - 14:15
Technical brief funrich: An open access standalone functional enrichment and interaction network analysis tool. Proteomics. 2015 Apr 29; Authors: Pathan M, Keerthikumar S, Ang CS, Gangoda L, Quek CY, Williamson NA, Mouradov D, Sieber OM, Simpson RJ, Salim A, Bacic A, Hill A, Stroud DA, Ryan MT, Agbinya JI, Mariadasson JM, Burgess AW, Mathivanan S Abstract As high-throughput techniques including proteomics become more accessible to individual laboratories, there is an urgent need for a user-friendly bioinformatics analysis system. Here, we describe FunRich, an open access, standalone functional enrichment and network analysis tool. FunRich is designed to be used by biologists with minimal or no support from computational and database experts. Using FunRich, users can perform functional enrichment analysis on background databases that are integrated from heterogeneous genomic and proteomic resources (>1.5 million annotations). Besides default human specific FunRich database, users can download data from the UniProt database which currently supports 20 different taxonomies against which enrichment analysis can be performed. Moreover, the users can build their own custom databases and perform the enrichment analysis irrespective of organism. In addition to proteomics datasets, the custom database allows for the tool to be used for genomics, lipidomics and metabolomics datasets. Thus FunRich allows for complete database customization and thereby permits for the tool to be exploited as a skeleton for enrichment analysis irrespective of the data type or organism used. FunRich is user-friendly and provides graphical representation (Venn, pie charts, bar graphs, column, heatmap and doughnuts) of the data with customizable font, scale and color (publication quality) This article is protected by copyright. All rights reserved. PMID: 25921073 [PubMed - as supplied by publisher]

[Analysis of metabolic profile of Chlamydomonas reinhardtii cultivated under autotrophic conditions].

Thu, 30/04/2015 - 14:15
Related Articles [Analysis of metabolic profile of Chlamydomonas reinhardtii cultivated under autotrophic conditions]. Prikl Biokhim Mikrobiol. 2015 Jan-Feb;51(1):73-85 Authors: Puzanskiĭ RK, Shavarda AL, Tarakhovskaia ER, Shishova MF Abstract This study presents a metabolite profile analysis of unicellular green alga Chlamydomonas reinhardtii grown under autotrophic conditions at late stages of culture development. Metabolites were identified by gas chromatography coupled to mass spectrometry. Approximately 400 peaks corresponding to individual compounds were distinguished, of which approximately 100 compounds (including saccharides, fatty acids, aromatic compounds, amino acids, alcohols, etc.) were identified. A local database of mass spectra of unidentified compounds was created using MassBank software. Mapping of the metabolomic data with the use of the ChlamyCyc service showed that the identified compounds are involved in various energetic, synthetic, and signaling pathways in Chlamydomonas. The mapping of metabolites by their chemical structure with the use of Cytoscape software, combined with quantitative interpretation, showed that the majority of organic matter was concentrated primarily in the carbon backbones of fatty acids and terpenes, as well as saccharides and structurally similar compounds. PMID: 25842907 [PubMed - indexed for MEDLINE]

[Reactivating factor of Luteococcus japonicus subsp. casei: isolation and characterization].

Thu, 30/04/2015 - 14:15
Related Articles [Reactivating factor of Luteococcus japonicus subsp. casei: isolation and characterization]. Prikl Biokhim Mikrobiol. 2015 Jan-Feb;51(1):37-45 Authors: Vorob'eva LI, Rogozhin EA, Khodzhaev EIu, Nikolaev IV, Turova TP Abstract It has been shown that a producer strain of reactivating factor (RF) is identical to a typical strain of Luteococcus japonicus DSM 10546 from the Propionibacteriaceae family according to the physiological and biochemical properties and the sequencing of 16S rRNA fragments. A number of phenotypical differences from the model strain allowed the producer strain to be considered a subspecies of Luteococcus japonicus, and it was named Luteococcus japonicus subsp. casei. At cultivation of the producer, RF is secreted into the medium and plays the role of a signaling molecule. RF antioxidant activities towards various organic radicals may be a possible mechanism of its protective and reactivating effects. Metabolites secreted by the L. casei producer strain into the culture medium were separated by a combination of liquid chromatographies. Four components possessing biological activities were found. The most active one was studied by MALDI-TOF mass spectrometry, which revealed that it is a polypeptide. Primary identification of some amino acid residues was performed. Sugar residues were found in the structure. PMID: 25842902 [PubMed - indexed for MEDLINE]

Metabolonote: a wiki-based database for managing hierarchical metadata of metabolome analyses.

Fri, 24/04/2015 - 17:17
Metabolonote: a wiki-based database for managing hierarchical metadata of metabolome analyses. Front Bioeng Biotechnol. 2015;3:38 Authors: Ara T, Enomoto M, Arita M, Ikeda C, Kera K, Yamada M, Nishioka T, Ikeda T, Nihei Y, Shibata D, Kanaya S, Sakurai N Abstract Metabolomics - technology for comprehensive detection of small molecules in an organism - lags behind the other "omics" in terms of publication and dissemination of experimental data. Among the reasons for this are difficulty precisely recording information about complicated analytical experiments (metadata), existence of various databases with their own metadata descriptions, and low reusability of the published data, resulting in submitters (the researchers who generate the data) being insufficiently motivated. To tackle these issues, we developed Metabolonote, a Semantic MediaWiki-based database designed specifically for managing metabolomic metadata. We also defined a metadata and data description format, called "Togo Metabolome Data" (TogoMD), with an ID system that is required for unique access to each level of the tree-structured metadata such as study purpose, sample, analytical method, and data analysis. Separation of the management of metadata from that of data and permission to attach related information to the metadata provide advantages for submitters, readers, and database developers. The metadata are enriched with information such as links to comparable data, thereby functioning as a hub of related data resources. They also enhance not only readers' understanding and use of data but also submitters' motivation to publish the data. The metadata are computationally shared among other systems via APIs, which facilitate the construction of novel databases by database developers. A permission system that allows publication of immature metadata and feedback from readers also helps submitters to improve their metadata. Hence, this aspect of Metabolonote, as a metadata preparation tool, is complementary to high-quality and persistent data repositories such as MetaboLights. A total of 808 metadata for analyzed data obtained from 35 biological species are published currently. Metabolonote and related tools are available free of cost at http://metabolonote.kazusa.or.jp/. PMID: 25905099 [PubMed]

Maternal hair metabolome analysis identifies a potential marker of lipid peroxidation in gestational diabetes mellitus.

Fri, 24/04/2015 - 17:17
Maternal hair metabolome analysis identifies a potential marker of lipid peroxidation in gestational diabetes mellitus. Acta Diabetol. 2015 Apr 24; Authors: He X, de Seymour JV, Sulek K, Qi H, Zhang H, Han TL, Villas-Bôas SG, Baker PN PMID: 25904507 [PubMed - as supplied by publisher]

Metabolomic analysis of prostate cancer risk in a prospective cohort: The alpha-tocopherol, beta-carotene cancer prevention study.

Fri, 24/04/2015 - 17:17
Metabolomic analysis of prostate cancer risk in a prospective cohort: The alpha-tocopherol, beta-carotene cancer prevention study. Int J Cancer. 2015 Apr 22; Authors: Mondul AM, Moore SC, Weinstein SJ, Karoly ED, Sampson JN, Albanes D Abstract Despite decades of concerted epidemiological research, relatively little is known about the etiology of prostate cancer. As genome-wide association studies have identified numerous genetic variants, so metabolomic profiling of blood and other tissues represents an agnostic, "broad-spectrum" approach for examining potential metabolic biomarkers of prostate cancer risk. To this end, we conducted a prospective analysis of prostate cancer within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort based on 200 cases (100 advanced) and 200 controls (age- and blood collection date-matched) with fasting serum collected up to 20 years prior to case diagnoses. Ultrahigh performance liquid chromatography/mass spectroscopy and gas chromatography/mass spectroscopy identified 626 compounds detected in >95% of the men, and the odds ratio per 1-standard deviation increase in log-metabolite levels and risk were estimated using conditional logistic regression. We observed strong inverse associations between energy and lipid metabolites and aggressive cancer (p=0.018 and p=0.041, respectively, for chemical class over-representation). Inositol-1-phosphate showed the strongest association (OR=0.56, 95% CI=0.39-0.81, p=0.002), and glycerophospholipids and fatty acids were heavily represented; e.g., oleoyl-linoleoyl-glycerophosphoinositol (OR=0.64, p=0.004), 1-stearoylglycerophosphoglycerol (OR=0.65, p=0.025), stearate (OR=0.65, p=0.010), and docosadienoate (OR=0.66, p=0.014). Both alpha-ketoglutarate and citrate were associated with aggressive disease risk (OR=0.69, 95% CI=0.51-0.94, p=0.02; OR=0.69, 95% CI=0.50-0.95, p=0.02), as were elevated thyroxine and trimethylamine oxide (TMAO) (OR=1.65, 95% CI=1.08-2.54, p=0.021; and, OR=1.36, 95% CI=1.02-1.81, p=0.039). Serum PSA adjustment did not alter the findings. Our data reveal several metabolomic leads that may have pathophysiological relevance to prostate carcinogenesis and should be examined through additional research. This article is protected by copyright. All rights reserved. PMID: 25904191 [PubMed - as supplied by publisher]

[Serum metabolomics analysis on benign prostate hyperplasia in mice based on liquid chromatography-mass spectrometry].

Fri, 24/04/2015 - 17:17
Related Articles [Serum metabolomics analysis on benign prostate hyperplasia in mice based on liquid chromatography-mass spectrometry]. Se Pu. 2014 Dec;32(12):1301-5 Authors: Geng Y, Sun F, Ma Y, Deng L, Lü J, Li T, Wang C Abstract Benign prostatic hyperplasia (BPH) increasingly becomes a common factor affecting the quality of life of aging men. Its pathogenesis has not yet been fully elucidated. Ultra-high pressure liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was employed to detect the changes of serum metabolites in normal mice, benign prostatic hyperplasia model mice and BPH model mice with finasteride intervention. The serum metabolite profiles of the three groups of mice were analyzed. Partial least squares-discriminant analysis (PLS-DA) was used for group differentiation and biomarker selection. The results showed good distinction among the three groups of mice serum metabolite spectra. Three potential biomarkers, 1-hexadecanoyl-SN-glycero-3-phosphocholine, 1-O-hexadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine and (Z)-13-docosenamide, were discovered and identified. They all indicated the occurrence of benign prostatic hypertrophy is closely related to the disorders of lipid metabolism. Coinpared with the control group, the contents of the first two substances were significantly increased in the serum of BPH model mice, and significantly decreased after intervened by finasteride. The contents of (Z)-13-docosenamide decreased significantly in the serum of model group, and increased after intervened by finasteride. Compared with the control group, the contents of three biomarkers in finasteride group did not recover completely and had significant differences. This study is conductive to open new avenues of diagnosis and medical treatment for BPH. PMID: 25902635 [PubMed - in process]

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