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

Activation of surrogate death receptor signaling triggers peroxynitrite-dependent execution of cisplatin-resistant cancer cells.

Wed, 22/06/2016 - 12:54
Related Articles Activation of surrogate death receptor signaling triggers peroxynitrite-dependent execution of cisplatin-resistant cancer cells. Cell Death Dis. 2015;6:e1926 Authors: Seah S, Low IC, Hirpara JL, Sachaphibulkij K, Kroemer G, Brenner C, Pervaiz S Abstract Platinum-based drugs remain as the cornerstone of cancer chemotherapy; however, development of multidrug resistance presents a therapeutic challenge. This study aims at understanding the molecular mechanisms underlying resistance to cisplatin and unraveling surrogate signaling networks that could revert sensitivity to apoptosis stimuli. We made use of three different sets of cell lines, A549 and H2030 non-small-cell lung cancer (NSCLC) and A2780 ovarian cancer cells and their cisplatin-resistant variants. Here we report that cisplatin-resistant cell lines displayed a multidrug-resistant phenotype. Changes in mitochondrial metabolism and defective mitochondrial signaling were unraveled in the resistant cells. More interestingly, a marked increase in sensitivity of the resistant cells to death receptor-induced apoptosis, in particular TRAIL (TNF-related apoptosis-inducing ligand)-mediated execution, was observed. Although this was not associated with an increase in gene transcription, a significant increase in the localization of TRAIL death receptor, DR4, to the lipid raft subdomains of plasma membrane was detected in the resistant variants. Furthermore, exposure of cisplatin-resistant cells to TRAIL resulted in upregulation of inducible nitric oxide synthase (iNOS) and increase in nitric oxide (NO) production that triggered the generation of peroxynitrite (ONOO(-)). Scavenging ONOO(-) rescued cells from TRAIL-induced apoptosis, thereby suggesting a critical role of ONOO(-) in TRAIL-induced execution of cisplatin-resistant cells. Notably, preincubation of cells with TRAIL restored sensitivity of resistant cells to cisplatin. These data provide compelling evidence for employing strategies to trigger death receptor signaling as a second-line treatment for cisplatin-resistant cancers. PMID: 26492363 [PubMed - indexed for MEDLINE]

metabolomics; +21 new citations

Tue, 21/06/2016 - 12:15
21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2016/06/21PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Time-resolved NMR metabolomics of plant cells based on a microfluidic chip.

Mon, 20/06/2016 - 14:28
Time-resolved NMR metabolomics of plant cells based on a microfluidic chip. J Plant Physiol. 2016 Jun 10;200:28-34 Authors: Maisch J, Kreppenhofer K, Büchler S, Merle C, Sobich S, Görling B, Luy B, Ahrens R, Guber AE, Nick P Abstract The plant secondary metabolism generates numerous compounds harbouring pharmaceutical activity. In plants, these compounds are typically formed by different and specialised cell types that have to interact constituting a metabolic process chain. This interactivity impedes biotechnological production of secondary compounds, because cell differentiation is suppressed under the conditions of a batch bio-fermenter. We present a novel strategy to address this limitation using a biomimetic approach, where we simulate the situation in a real tissue by a microfluidic chamber system, where plant cells can be integrated into a process flow. We show that walled cells of the plant model tobacco BY-2 can be successfully cultivated in this system and that physiological parameters (such as cell viability, mitotic index and division synchrony) can be preserved over several days. The microfluidic design allows to resolve dynamic changes of specific metabolites over different stages of culture development. These results serve as proof-of-principle that a microfluidic organisation of cultivated plant cells can mimic the metabolic flows in a real plant tissue. PMID: 27318870 [PubMed - as supplied by publisher]

Global metabolite analysis of the land snail Theba pisana hemolymph during active and aestivated states.

Mon, 20/06/2016 - 14:28
Global metabolite analysis of the land snail Theba pisana hemolymph during active and aestivated states. Comp Biochem Physiol Part D Genomics Proteomics. 2016 Jun 6;19:25-33 Authors: Bose U, Centurion E, Hodson MP, Shaw PN, Storey KB, Cummins SF Abstract The state of metabolic dormancy has fascinated people for hundreds of years, leading to research exploring the identity of natural molecular components that may induce and maintain this state. Many animals lower their metabolism in response to high temperatures and/or arid conditions, a phenomenon called aestivation. The biological significance for this is clear; by strongly suppressing metabolic rate to low levels, animals minimize their exposure to stressful conditions. Understanding blood or hemolymph metabolite changes that occur between active and aestivated animals can provide valuable insights relating to those molecular components that regulate hypometabolism in animals, and how they afford adaptation to their different environmental conditions. In this study, we have investigated the hemolymph metabolite composition from the land snail Theba pisana, a remarkably resilient mollusc that displays an annual aestivation period. Using LC-MS-based metabolomics analysis, we have identified those hemolymph metabolites that show significant changes in relative abundance between active and aestivated states. We show that certain metabolites, including some phospholipids [e.g. LysoPC(14:0)], and amino acids such as l-arginine and l-tyrosine, are present at high levels within aestivated snails. Further investigation of our T. pisana RNA-sequencing data elucidated the entire repertoire of phospholipid-synthesis genes in the snail digestive gland, as a precursor towards future comparative investigation between the genetic components of aestivating and non-aestivating species. In summary, we have identified a large number of metabolites that are elevated in the hemolymph of aestivating snails, supporting their role in protecting against heat or desiccation. PMID: 27318654 [PubMed - as supplied by publisher]

Response and Defense Mechanisms of Taxus chinensis leaves under UV-A Radiation are Revealed Using Comparative Proteomics and Metabolomics Analyses.

Sun, 19/06/2016 - 13:56
Response and Defense Mechanisms of Taxus chinensis leaves under UV-A Radiation are Revealed Using Comparative Proteomics and Metabolomics Analyses. Plant Cell Physiol. 2016 Jun 18; Authors: Zheng W, Komatsu S, Zhu W, Zhang L, Li X, Cui L, Tian J Abstract Taxus chinensis var. mairei is an endemic species to southeastern China and one of the natural sources for the anticancer medicine paclitaxel. To investigate the molecular response and defense mechanisms of T. chinensis leaves to enhanced ultraviolet-A (UV-A) radiation, gel-free/label-free and gel-based proteomics and GC-MS analyses were performed. The transmission electron microscopy results indicated damage on chloroplast under UV-A radiation. Proteomics analyses in leaves and chloroplast showed that photosynthesis-, glycolysis-, secondary metabolism-, stress-, and protein synthesis, degradation, and activation- related systems were mainly changed under UV-A radiation. Forty-seven PS II proteins and six PS I proteins were identified changed in leaves and chloroplast under UV-A treatment. It indicated that PS II was more sensitive to UV-A than PS I as UV-A light target. Enhanced glycolysis, with four glycolysis-related key enzymes increased, provided precursors for secondary metabolism. The 1-deoxy-D-xylulose-5-phosphate reductoisomerase and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase were identified significantly increased during UV-A radiation, which resulted in paclitaxel enhancement. Additionally, mRNA expression levels of genes involved in the paclitaxel biosynthetic pathway indicated a down-regulation under UV-A irradiation and up-regulation in dark incubation. These results reveal that a short-term high dose of UV-A radiation could stimulate the plant stress defense system and paclitaxel production. PMID: 27318281 [PubMed - as supplied by publisher]

Metabolic and biochemical changes in streptozotocin induced obese-diabetic rats treated with Phyllanthus niruri extract.

Sun, 19/06/2016 - 13:56
Metabolic and biochemical changes in streptozotocin induced obese-diabetic rats treated with Phyllanthus niruri extract. J Pharm Biomed Anal. 2016 Jun 4;128:302-312 Authors: Mediani A, Abas F, Maulidiani M, Khatib A, Tan CP, Ismail IS, Shaari K, Ismail A, Lajis NH Abstract Herbal medicine has been proven to be an effective therapy offering a variety of benefits, such as moderate reduction in hypoglycemia, in the treatment and prevention of obesity and diabetes. Phyllanthus niruri has been used as a treatment for diabetes mellitus. Herein, the induction of type 2 diabetes in Sprague-Dawley rats was achieved by a low dose of streptozotocin (STZ) (25mg/kgbw). Here, we evaluated the in vivo antidiabetic properties of two concentrations (250 and 500mg/kg bw) of P. niruri via metabolomics approach. The administration of 500mg/kgbw of P. niruri extract caused the metabolic disorders of obese diabetic rats to be improved towards the normal state. The extract also clearly decreased the serum glucose level and improved the lipid profile in obese diabetic rats. The results of this study may contribute towards better understanding the molecular mechanism of this medicinal plant in managing diabetes mellitus. PMID: 27318080 [PubMed - as supplied by publisher]

Staphylococcus aureus methicillin resistance detected by HPLC-MS/MS targeted metabolic profiling.

Sun, 19/06/2016 - 13:56
Staphylococcus aureus methicillin resistance detected by HPLC-MS/MS targeted metabolic profiling. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jun 3; Authors: Schelli K, Rutowski J, Roubidoux J, Zhu J Abstract Recently, novel bioanalytical methods, such as NMR and mass spectrometry based metabolomics approaches, have started to show promise in providing rapid, sensitive and reproducible detection of Staphylococcus aureus antibiotic resistance. Here we performed a proof-of-concept study focused on the application of HPLC-MS/MS based targeted metabolic profiling for detecting and monitoring the bacterial metabolic profile changes in response to sub-lethal levels of methicillin exposure. One hundred seventy-seven targeted metabolites from over 20 metabolic pathways were specifically screened and one hundred and thirty metabolites from in vitro bacterial tests were confidently detected from both methicillin susceptible and methicillin resistant Staphylococcus aureus (MSSA and MRSA, respectively). The metabolic profiles can be used to distinguish the isogenic pairs of MSSA strains from MRSA strains, without or with sub-lethal levels of methicillin exposure. In addition, better separation between MSSA and MRSA strains can be achieved in the latter case using principal component analysis (PCA). Metabolite data from isogenic pairs of MSSA and MRSA strains were further compared without and with sub-lethal levels of methicillin exposure, with metabolic pathway analyses additionally performed. Both analyses suggested that the metabolic activities of MSSA strains were more susceptible to the perturbation of the sub-lethal levels of methicillin exposure compared to the MRSA strains. PMID: 27316783 [PubMed - as supplied by publisher]

Biotransformation and metabolic profile of caudatin-2,6-dideoxy-3-O-methy-β-d-cymaropyranoside with human intestinal microflora by liquid chromatography quadrupole time-of-flight mass spectrometry.

Sun, 19/06/2016 - 13:56
Related Articles Biotransformation and metabolic profile of caudatin-2,6-dideoxy-3-O-methy-β-d-cymaropyranoside with human intestinal microflora by liquid chromatography quadrupole time-of-flight mass spectrometry. Biomed Chromatogr. 2015 Nov;29(11):1715-23 Authors: Zhang W, Peng YR, Ding YF Abstract In our previous studies, caudatin-2,6-dideoxy-3-O-methy-β-d- cymaropyranoside (CDMC) was for the first time isolated from Cynanchum auriculatum Royle ex Wightand and was reported to possess a wide range of biological activities. However, the routes and metabolites of CDMC produced by intestinal bacteria are not well understood. In this study, ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) technique combined with Metabolynx(TM) software was applied to analyze metabolites of CDMC by human intestinal bacteria. The incubated samples collected for 48 h in an anaerobic incubator and extracted with ethyl acetate were analyzed by UPLC-Q-TOF-MS within 12 min. Eight metabolites were identified based on MS and MS/MS data. The results indicated that hydrolysis, hydrogenation, demethylation and hydroxylation were the major metabolic pathways of CDMC in vitro. Seven strains of bacteria including Bacillus sp. 46, Enterococcus sp. 30 and sp. 45, Escherichia sp. 49A, sp. 64, sp. 68 and sp. 75 were further identified using 16S rRNA gene sequencing owing to their relatively strong metabolic capacity toward CDMC. The present study provides important information about metabolic routes of CDMC and the roles of different intestinal bacteria in the metabolism of CDMC. Moreover, those metabolites might influence the biological effect of CDMC in vivo, which affects the clinical effects of this medicinal plant. PMID: 26018801 [PubMed - indexed for MEDLINE]

Multi-omics Frontiers in Algal Research: Techniques and Progress to Explore Biofuels in the Postgenomics World.

Sat, 18/06/2016 - 13:00
Multi-omics Frontiers in Algal Research: Techniques and Progress to Explore Biofuels in the Postgenomics World. OMICS. 2016 Jun 17; Authors: Rai V, Karthikaichamy A, Das D, Noronha S, Wangikar PP, Srivastava S Abstract Current momentum of microalgal research rests extensively in tapping the potential of multi-omics methodologies in regard to sustainable biofuels. Microalgal biomass is fermented to bioethanol; while lipids, particularly triacylglycerides (TAGs), are transesterified to biodiesels. Biodiesel has emerged as an ideal biofuel candidate; hence, its commercialization and use are increasingly being emphasized. Abiotic stresses exaggerate TAG accumulation, but the precise mechanisms are yet to be known. More recently, comprehensive multi-omics studies in microalgae have emerged from the biofuel perspective. Genomics and transcriptomics of microalgae have provided crucial leads and basic understanding toward lipid biosynthesis. Proteomics and metabolomics are now complementing "algal omics" and offer precise functional insights into the attendant static and dynamic physiological contexts. Indeed, the field has progressed from shotgun to targeted approaches. Notably, targeted proteomics studies in microalga are not yet reported. Several multi-omics tools and technologies that may be used to dig deeper into the microalgal physiology are examined and highlighted in this review. The article therefore aims to both introduce various available high-throughput biotechnologies and applications of "omics" in microalgae, and enlists a compendium of the emerging cutting edge literature. We suggest that a strategic and thoughtful combination of data streams from different omics platforms can provide a system-wide overview. The algal omics warrants closer attention in the future, with a view to technical, economic, and societal impacts that are anticipated in the current postgenomics era. PMID: 27315140 [PubMed - as supplied by publisher]

Precision medicine of aneurysmal subarachnoid hemorrhage, vasospasm and delayed cerebral ischemia.

Sat, 18/06/2016 - 13:00
Precision medicine of aneurysmal subarachnoid hemorrhage, vasospasm and delayed cerebral ischemia. Expert Rev Neurother. 2016 Jun 17; Authors: Burrell C, Avalon NE, Siegel J, Pizzi M, Dutta T, Charlesworth MC, Freeman WD Abstract INTRODUCTION: Precision medicine is an emerging paradigm aimed at providing individualized prevention and treatment of diseases through understanding and leveraging patient-to-patient variation. Aneurysmal subarachnoid hemorrhage (aSAH) carries tremendous morbidity and mortality with subsequent cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) proving devastating and unpredictable. The paucity of effective treatment or prevention measures for these conditions could potentially be improved through implementation of precision medicine. AREAS COVERED: This review presents the basic pathophysiology of CV and DCI, current treatment guidelines, and evidence for the use of precision medicine in the prediction and prevention of poor outcomes following aSAH. An extensive PubMed literature search was performed using keywords cerebral vasospasm or delayed cerebral ischemia and either biomarkers, precision medicine, metabolomics, proteomics, or genomics. Over 200 peer-reviewed articles were reviewed. The studies presented focus on biomarkers identified as predictive markers or therapeutic targets following aSAH. Expert Commentary: The array of novel biomarkers reviewed here, ranging from genotypes to metabolites, has been found to correlate with CV, DCI, and neurologic outcomes after aSAH. Though their practical use in the clinical management of aSAH is not well established, using these biomarkers as predictive tools or therapeutic targets demonstrates the potential of precision medicine in the treatment of aSAH. PMID: 27314601 [PubMed - as supplied by publisher]

Metabolomic Profiles of Aspergillus oryzae and Bacillus amyloliquefaciens During Rice Koji Fermentation.

Sat, 18/06/2016 - 13:00
Metabolomic Profiles of Aspergillus oryzae and Bacillus amyloliquefaciens During Rice Koji Fermentation. Molecules. 2016;21(6) Authors: Lee DE, Lee S, Jang ES, Shin HW, Moon BS, Lee CH Abstract Rice koji, used early in the manufacturing process for many fermented foods, produces diverse metabolites and enzymes during fermentation. Using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS), ultrahigh-performance liquid chromatography linear trap quadrupole ion trap tandem mass spectrometry (UHPLC-LTQ-IT-MS/MS), and multivariate analysis we generated the metabolite profiles of rice koji produced by fermentation with Aspergillus oryzae (RK_AO) or Bacillus amyloliquefaciens (RK_BA) for different durations. Two principal components of the metabolomic data distinguished the rice koji samples according to their fermenter species and fermentation time. Several enzymes secreted by the fermenter species, including α-amylase, protease, and β-glucosidase, were assayed to identify differences in expression levels. This approach revealed that carbohydrate metabolism, serine-derived amino acids, and fatty acids were associated with rice koji fermentation by A. oryzae, whereas aromatic and branched chain amino acids, flavonoids, and lysophospholipids were more typical in rice koji fermentation by B. amyloliquefaciens. Antioxidant activity was significantly higher for RK_BA than for RK_AO, as were the abundances of flavonoids, including tricin, tricin glycosides, apigenin glycosides, and chrysoeriol glycosides. In summary, we have used MS-based metabolomics and enzyme activity assays to evaluate the effects of using different microbial species and fermentation times on the nutritional profile of rice koji. PMID: 27314317 [PubMed - as supplied by publisher]

Genomics and Metabolomics in Obesity and Type 2 Diabetes.

Sat, 18/06/2016 - 13:00
Genomics and Metabolomics in Obesity and Type 2 Diabetes. J Diabetes Res. 2016;2016:9415645 Authors: Kretowski A, Ruperez FJ, Ciborowski M PMID: 27314051 [PubMed - in process]

Associations between plasma branched-chain amino acids, β-aminoisobutyric acid and body composition.

Sat, 18/06/2016 - 13:00
Associations between plasma branched-chain amino acids, β-aminoisobutyric acid and body composition. J Nutr Sci. 2016;5:e6 Authors: Rietman A, Stanley TL, Clish C, Mootha V, Mensink M, Grinspoon SK, Makimura H Abstract Plasma branched-chain amino acids (BCAA) are elevated in obesity and associated with increased cardiometabolic risk. β-Aminoisobutyric acid (B-AIBA), a recently identified small molecule metabolite, is associated with decreased cardiometabolic risk. Therefore, we investigated the association of BCAA and B-AIBA with each other and with detailed body composition parameters, including abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). A cross-sectional study was carried out with lean (n 15) and obese (n 33) men and women. Detailed metabolic evaluations, including measures of body composition, insulin sensitivity and plasma metabolomics were completed. Plasma BCAA were higher (1·6 (se 0·08) (×10(7)) v. 1·3 (se 0·06) (×10(7)) arbitrary units; P = 0·005) in obese v. lean subjects. BCAA were positively associated with VAT (R 0·49; P = 0·0006) and trended to an association with SAT (R 0·29; P = 0·052). The association between BCAA and VAT, but not SAT, remained significant after controlling for age, sex and race on multivariate modelling (P < 0·05). BCAA were also associated with parameters of insulin sensitivity (Matsuda index: R -0·50, P = 0·0004; glucose AUC: R 0·53, P < 0·001). BCAA were not associated with B-AIBA (R -0·04; P = 0·79). B-AIBA was negatively associated with SAT (R -0·37; P = 0·01) but only trended to an association with VAT (R 0·27; P = 0·07). However, neither relationship remained significant after multivariate modelling (P > 0·05). Plasma B-AIBA was associated with parameters of insulin sensitivity (Matsuda index R 0·36, P = 0·01; glucose AUC: R -0·30, P = 0·04). Plasma BCAA levels were positively correlated with VAT and markers of insulin resistance. The results suggest a possible complex role of adipose tissue in BCAA homeostasis and insulin resistance. PMID: 27313851 [PubMed]

The LINA Study: Higher Sensitivity of Infant Compared to Maternal Eosinophil/Basophil Progenitors to Indoor Chemical Exposures.

Sat, 18/06/2016 - 13:00
The LINA Study: Higher Sensitivity of Infant Compared to Maternal Eosinophil/Basophil Progenitors to Indoor Chemical Exposures. J Environ Public Health. 2016;2016:5293932 Authors: Hörnig F, Kohajda T, Röder S, Herberth G, von Bergen M, Borte M, Diez U, Rolle-Kampczyk U, Simon JC, Denburg JA, Lehmann I, Junge KM Abstract Purpose. Enhanced eosinophil/basophil (Eo/B) progenitor cell levels are known to be associated with allergic inflammation and atopy risk. The aim of the present study was to investigate the influence of different indoor exposures on the recruitment and differentiation of Eo/B progenitors in mother-child pairs. Methods. In 68 mother-child pairs of the LINA study peripheral blood mononuclear cells were used to assess Eo/B colony forming units (CFUs). Information about disease outcomes and indoor exposures was obtained from questionnaires. Indoor concentrations of volatile organic compounds (VOCs) were measured by passive sampling. Results. Infant's Eo/B CFUs were positively associated with exposure to tobacco smoke, disinfectants, or VOCs. In contrast, for maternal Eo/B CFUs, only a few associations were seen. Higher numbers of infant Eo/B CFUs were observed in children with wheezing symptoms within the second year of life. Conclusions. We demonstrate that infant's hematopoietic cells seem to respond with more sensitivity to environmental exposure compared to maternal cells. At least in infants, an activation of these hematopoietic cells by environmental exposure could contribute to an enhanced risk for the development of respiratory outcomes. PMID: 27313631 [PubMed - in process]

Application of a Smartphone Metabolomics Platform to the Authentication of Schisandra sinensis.

Sat, 18/06/2016 - 13:00
Application of a Smartphone Metabolomics Platform to the Authentication of Schisandra sinensis. Phytochem Anal. 2016 May;27(3-4):199-205 Authors: Kwon HN, Phan HD, Xu WJ, Ko YJ, Park S Abstract INTRODUCTION: Herbal medicines have been used for a long time all around the world. Since the quality of herbal preparations depends on the source of herbal materials, there has been a strong need to develop methods to correctly identify the origin of materials. OBJECTIVE: To develop a smartphone metabolomics platform as a simpler and low-cost alternative for the identification of herbal material source. METHODOLOGY: Schisandra sinensis extracts from Korea and China were prepared. The visible spectra of all samples were measured by a smartphone spectrometer platform. This platform included all the necessary measures built-in for the metabolomics research: data acquisition, processing, chemometric analysis and visualisation of the results. The result of the smartphone metabolomics platform was compared to that of NMR-based metabolomics, suggesting the feasibility of smartphone platform in metabolomics research. RESULTS: The smartphone metabolomics platform gave similar results to the NMR method, showing good separation between Korean and Chinese materials and correct predictability for all test samples. CONCLUSION: With its accuracy and advantages of affordability, user-friendliness, and portability, the smartphone metabolomics platform could be applied to the authentication of other medicinal plants. Copyright © 2016 John Wiley & Sons, Ltd. PMID: 27313157 [PubMed - in process]

In situ Identification of Labile Precursor Compounds and their Short-lived Intermediates in Plants using in vivo Nanospray High-resolution Mass Spectrometry.

Sat, 18/06/2016 - 13:00
In situ Identification of Labile Precursor Compounds and their Short-lived Intermediates in Plants using in vivo Nanospray High-resolution Mass Spectrometry. Phytochem Anal. 2016 May;27(3-4):184-90 Authors: Chang Q, Peng Y, Shi B, Dan C, Yang Y, Shuai Q Abstract INTRODUCTION: Many secondary metabolites in plants are labile compounds which under environmental stress, are difficult to detect and track due to the lack of rapid in situ identification techniques, making plant metabolomics research difficult. Therefore, developing a reliable analytical method for rapid in situ identification of labile compounds and their short-lived intermediates in plants is of great importance. OBJECTIVE: To develop under atmospheric pressure, a rapid in situ method for effective identification of labile compounds and their short-lived intermediates in fresh plants. METHODOLOGY: An in vivo nanospray high-resolution mass spectrometry (HR-MS) method was used for rapid capture of labile compounds and their short-lived intermediates in plants. A quartz capillary was partially inserted into fresh plant tissues, and the liquid flowed out through the capillary tube owing to the capillary effect. A high direct current (d.c.) voltage was applied to the plant to generate a spray of charged droplets from the tip of the capillary carrying bioactive molecules toward the inlet of mass spectrometer for full-scan and MS/MS analysis. RESULTS: Many labile compounds and short-lived intermediates were identified via this method: including glucosinolates and their short-lived intermediates (existing for only 10 s) in Raphanus sativus roots, alliin and its conversion intermediate (existing for 20 s) in Allium sativum and labile precursor compound chlorogenic acid in Malus pumila Mill. CONCLUSION: The method is an effective approach for in situ identification of internal labile compounds and their short-lived intermediates in fresh plants and it can be used as an auxiliary tool to explore the degradation mechanisms of new labile plant compounds. Copyright © 2016 John Wiley & Sons, Ltd. PMID: 27313155 [PubMed - in process]

Elucidation of ethanol tolerance mechanisms in Saccharomyces cerevisiae by global metabolite profiling.

Sat, 18/06/2016 - 13:00
Elucidation of ethanol tolerance mechanisms in Saccharomyces cerevisiae by global metabolite profiling. Biotechnol J. 2016 Jun 17; Authors: Kim S, Kim J, Song JH, Jung YH, Choi IS, Choi W, Park YC, Seo JH, Kim KH Abstract Ethanol, the major fermentation product of yeast, is a stress factor in yeast. We previously constructed an ethanol-tolerant mutant yeast iETS3 by using the global transcriptional machinery engineering. However, the ethanol-tolerance mechanism has not been systematically investigated. In this study, global metabolite profiling was carried out, mainly by gas chromatography/time-of-flight mass spectrometry (GC/TOF MS), to investigate the mechanisms of ethanol tolerance in iETS3. A total of 108 intracellular metabolites were identified by GC/TOF MS and high performance liquid chromatography, and these metabolites were mostly intermediates of the central carbon metabolism. The metabolite profiles of iETS3 and BY4741, cultured with or without ethanol, were significantly different based on principal component and hierarchical clustering analyses. Our metabolomic analyses identified the compositional changes in cell membranes and the activation of glutamate metabolism and the trehalose synthetic pathway as the possible mechanisms for the ethanol tolerance. These metabolic traits can be considered possible targets for further improvement of ethanol tolerance in the mutant. For example, the KGD1 deletion mutant, with up-regulated glutamate metabolism, showed increased tolerance to ethanol. This study has demonstrated that metabolomics can be a useful tool for strain improvement and phenotypic analysis of microorganisms under stress. PMID: 27313052 [PubMed - as supplied by publisher]

Biodiversity in marine invertebrate responses to acute warming revealed by a comparative multi-omics approach.

Sat, 18/06/2016 - 13:00
Biodiversity in marine invertebrate responses to acute warming revealed by a comparative multi-omics approach. Glob Chang Biol. 2016 Jun 17; Authors: Clark MS, Sommer U, Sihra JK, Thorne MA, Morley SA, King M, Viant MR, Peck LS Abstract Understanding species' responses to environmental change underpins our abilities to make predictions on future biodiversity under any range of scenarios. In spite of the huge biodiversity in most ecosystems, a model species approach is often taken in environmental studies. To date, we still do not know how many species we need to study to input into models and inform on ecosystem-level responses to change. In this study, we tested current paradigms on factors setting thermal limits by investigating the acute warming response of six Antarctic marine invertebrates: a crustacean Paraceradocus miersi, a brachiopod Liothyrella uva, two bivalve molluscs, Laternula elliptica, Aequiyoldia eightsii, a gastropod mollusc Marseniopsis mollis and an echinoderm Cucumaria georgiana. Each species was warmed at the rate of 1 °C h(-1) and taken to the same physiological end point (just prior to heat coma). Their molecular responses were evaluated using complementary metabolomics and transcriptomics approaches with the aim of discovering the underlying mechanisms of their resilience or sensitivity to warming. The responses were species-specific; only two showed accumulation of anaerobic end products and three exhibited the classical heat shock response with expression of HSP70 transcripts. These diverse cellular measures did not directly correlate with resilience to heat stress and suggested that each species may have a different critical point of failure. Thus, one unifying molecular mechanism underpinning response to warming could not be assigned, and no overarching paradigm was supported. This biodiversity in response makes future ecosystems predictions extremely challenging, as we clearly need to develop a macrophysiology-type approach to cellular evaluations of the environmental stress response, studying a range of well-rationalized members from different community levels and of different phylogenetic origins rather than extrapolating from one or two arbitrary model species. PMID: 27312151 [PubMed - as supplied by publisher]

metabolomics; +19 new citations

Fri, 17/06/2016 - 12:29
19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2016/06/17PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice.

Thu, 16/06/2016 - 14:40
Related Articles Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice. Cell Metab. 2016 Jun 14;23(6):1093-1112 Authors: Mitchell SJ, Madrigal-Matute J, Scheibye-Knudsen M, Fang E, Aon M, González-Reyes JA, Cortassa S, Kaushik S, Gonzalez-Freire M, Patel B, Wahl D, Ali A, Calvo-Rubio M, Burón MI, Guiterrez V, Ward TM, Palacios HH, Cai H, Frederick DW, Hine C, Broeskamp F, Habering L, Dawson J, Beasley TM, Wan J, Ikeno Y, Hubbard G, Becker KG, Zhang Y, Bohr VA, Longo DL, Navas P, Ferrucci L, Sinclair DA, Cohen P, Egan JM, Mitchell JR, Baur JA, Allison DB, Anson RM, Villalba JM, Madeo F, Cuervo AM, Pearson KJ, Ingram DK, Bernier M, de Cabo R Abstract Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented age-associated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions. PMID: 27304509 [PubMed - as supplied by publisher]

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