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

Metabolomics sampling of Pichia pastoris revisited: rapid filtration prevents metabolite loss during quenching.

Sun, 21/06/2015 - 13:31
Related Articles Metabolomics sampling of Pichia pastoris revisited: rapid filtration prevents metabolite loss during quenching. FEMS Yeast Res. 2015 Jun 19; Authors: Russmayer H, Troyer C, Neubauer S, Steiger MG, Gasser B, Hann S, Koellensperger G, Sauer M, Mattanovich D Abstract Metabolomics can be defined as the quantitative assessment of a large number of metabolites of a biological system. A prerequisite for the accurate determination of intracellular metabolite concentrations is a reliable and reproducible sample preparation method, which needs to be optimized for each organism individually. Here we compare the performance of rapid filtration and centrifugation after quenching of Pichia pastoris cells in cold methanol. During incubation in the quenching solution metabolites are lost from the cells with a half-life of 70-180 min. Metabolites with lower molecular weights showed lower half-lifes compared to metabolites with higher molecular weight. Rapid filtration within 2 min after quenching leads to only minor losses below 2%, and is thus the preferred method for cell separation. PMID: 26091839 [PubMed - as supplied by publisher]

Metabolomics to Explore Impact of Dairy Intake.

Sat, 20/06/2015 - 13:08
Metabolomics to Explore Impact of Dairy Intake. Nutrients. 2015;7(6):4875-4896 Authors: Zheng H, Clausen MR, Dalsgaard TK, Bertram HC Abstract Dairy products are an important component in the Western diet and represent a valuable source of nutrients for humans. However, a reliable dairy intake assessment in nutrition research is crucial to correctly elucidate the link between dairy intake and human health. Metabolomics is considered a potential tool for assessment of dietary intake instead of traditional methods, such as food frequency questionnaires, food records, and 24-h recalls. Metabolomics has been successfully applied to discriminate between consumption of different dairy products under different experimental conditions. Moreover, potential metabolites related to dairy intake were identified, although these metabolites need to be further validated in other intervention studies before they can be used as valid biomarkers of dairy consumption. Therefore, this review provides an overview of metabolomics for assessment of dairy intake in order to better clarify the role of dairy products in human nutrition and health. PMID: 26091233 [PubMed - as supplied by publisher]

The role of genomics to identify biomarkers and signaling molecules during severe sepsis.

Sat, 20/06/2015 - 13:08
The role of genomics to identify biomarkers and signaling molecules during severe sepsis. Minerva Anestesiol. 2015 Jun 19; Authors: Douglas JJ, Russell JA Abstract Early strategies to diagnose, manage and predict outcome of sepsis are essential to further improve morbidity and mortality of sepsis. Whereas biomarkers have become mainstay in other fields of medicine, their clinical utility in sepsis remains generally much less proven and so biomarkers are much less used clinically. The Human Genome Project embellished genomics, transcriptomics, proteomics and metabolomics and continues to expand our knowledge of the genetic, gene expression, protein translational and metabolic discoveries that could lead to clinical biomarker tests related to sepsis thereby allowing insight into the disease as never seen before. We explore the genomic approach to biomarker identification and validation by reviewing pertinent studies related to the diagnosis (diagnostic biomarkers), prediction of response to therapies (predictive biomarkers) and (prognostic biomarkers) outcomes of sepsis. PMID: 26091010 [PubMed - as supplied by publisher]

Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species.

Sat, 20/06/2015 - 13:08
Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species. Int J Mol Sci. 2015;16(6):13850-13867 Authors: Lee KC, Tam EW, Lo KC, Tsang AK, Lau CC, To KK, Chan JF, Lam CW, Yuen KY, Lau SK, Woo PC Abstract Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, by comparing the metabolomic profiles of the culture supernatants of 30 strains of six pathogenic Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, A. nomius and A. tamarii) and 31 strains of 10 non-Aspergillus fungi, eight compounds present in all strains of the six Aspergillus species but not in any strain of the non-Aspergillus fungi were observed. One of the eight compounds, Leu-Glu-Leu-Glu, is a novel tetrapeptide and represents the first linear tetrapeptide observed in Aspergillus species, which we propose to be named aspergitide. Two other closely related Aspergillus-specific compounds, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid, may possess anti-inflammatory properties, as 2-(sulfooxy)benzoic acid possesses a structure similar to those of aspirin [2-(acetoxy)benzoic acid] and salicylic acid (2-hydroxybenzoic acid). Further studies to examine the potentials of these Aspergillus-specific compounds for laboratory diagnosis of aspergillosis are warranted and further experiments will reveal whether Leu-Glu-Leu-Glu, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid are virulent factors of the pathogenic Aspergillus species. PMID: 26090713 [PubMed - as supplied by publisher]

Metabolomics for Biomarker Discovery: Moving to the Clinic.

Sat, 20/06/2015 - 13:08
Related Articles Metabolomics for Biomarker Discovery: Moving to the Clinic. Biomed Res Int. 2015;2015:354671 Authors: Zhang A, Sun H, Yan G, Wang P, Wang X Abstract To improve the clinical course of diseases, more accurate diagnostic and assessment methods are required as early as possible. In order to achieve this, metabolomics offers new opportunities for biomarker discovery in complex diseases and may provide pathological understanding of diseases beyond traditional technologies. It is the systematic analysis of low-molecular-weight metabolites in biological samples and has become an important tool in clinical research and the diagnosis of human disease and has been applied to discovery and identification of the perturbed pathways. It provides a powerful approach to discover biomarkers in biological systems and offers a holistic approach with the promise to clinically enhance diagnostics. When carried out properly, it could provide insight into the understanding of the underlying mechanisms of diseases, help to identify patients at risk of disease, and predict the response to specific treatments. Currently, metabolomics has become an important tool in clinical research and the diagnosis of human disease and becomes a hot topic. This review will highlight the importance and benefit of metabolomics for identifying biomarkers that accurately screen potential biomarkers of diseases. PMID: 26090402 [PubMed - in process]

Metabolomics: A Tool Ahead for Understanding Molecular Mechanisms of Drugs and Diseases.

Sat, 20/06/2015 - 13:08
Related Articles Metabolomics: A Tool Ahead for Understanding Molecular Mechanisms of Drugs and Diseases. Indian J Clin Biochem. 2015 Jul;30(3):247-54 Authors: Shah NJ, Sureshkumar S, Shewade DG Abstract To refer to metabolomics as a new field is injustice to ancient doctors who used ants to diagnose the patients of diabetes having glycosuria. Measuring the levels of molecules in biological fluids believing them to be the representatives of biochemical pathways of carbohydrates, fats, proteins, nucleic acids or xenobiotic metabolism and deciphering meaningful data from it is what can be called as metabolomics, just as high glucose in urine suggests diabetes mellitus. Genomics, epigenetics, proteomics, transcriptomics finally converge to metabolomics, which are the signatures of mechanisms of bodily processes which is why understanding this science can have many applications. Just as a heap of stones does not make a house, having data of metabolite levels does not make it a science. Analyzing this data would help us in constructing biochemical pathways and their interactions. Analyzing the changes caused by a drug in the metabolite levels would help us in deriving the mechanisms by which the drug acts. Comparing metabolite levels in diseased with non-diseased, good-responders with poor-responders to a particular drug can help in identifying new markers of a disease or response to a drug respectively. Also, metabolite levels of an endogenous substrate can tell us the status of a person's metabolizing enzymes and help in drug dose titration. Generating hypothesis by identifying the new molecular markers and testing their utility in clinics seems to be the most promising approach in future. This review narrates the modes of quantifying and identifying metabolome, its proposed applications in diagnosis, monitoring and understanding the diseases and drug responses. We also intend to identify hindrances in using metabolomics in clinical studies or experiments. PMID: 26089608 [PubMed]

Metabolomic Analysis Using Liquid Chromatography/Mass Spectrometry for Gastric Cancer.

Sat, 20/06/2015 - 13:08
Related Articles Metabolomic Analysis Using Liquid Chromatography/Mass Spectrometry for Gastric Cancer. Appl Biochem Biotechnol. 2015 Jun 19; Authors: Liang Q, Wang C, Li B Abstract Metabolomics is a post-genomics research field for analysis of low molecular weight compounds in biological samples and has shown great potentials for elucidating complex mechanisms associated with diseases. However, metabolomics studies on gastric cancer (GC), which is the second leading cause of cancer death worldwide, remain scarce, and the molecular mechanisms to metabolomics phenotypes are also still not fully understood. This study reports that the metabolic pathways can be exploited as biomarkers for diagnosis and treatment of GC progression as a case study. Importantly, the urinary metabolites and metabolic patterns were analyzed by high-throughput liquid chromatography mass spectrometry (LC-MS) metabolomics strategy coupled with chemometric evaluation. Sixteen metabolites (nine upregulated and seven downregulated) were differentially expressed and may thus serve as potential urinary biomarkers for human GC. These metabolites were mainly involved in multiple metabolic pathways, including citrate cycle (malic acid, succinic acid, 2-oxoglutarate, citric acid), cyanoamino acid metabolism (glycine, alanine), primary bile acid biosynthesis (glycine, taurine, glycocholic acid), arginine and proline metabolism (urea, L-proline), and fatty acid metabolism (hexadecanoic acid), among others. Network analysis validated close association between these identified metabolites and altered metabolic pathways in a variety of biological processes. These results suggest that urine metabolic profiles have great potential in detecting GC and may aid in understanding its underlying mechanisms. It provides insight into disease pathophysiology and can serve as the basis for developing disease biomarkers and therapeutic interventions for GC diseases. PMID: 26088916 [PubMed - as supplied by publisher]

Analysis of the human adult urinary metabolome variations with age, body mass index and gender by implementing a comprehensive workflow for univariate and OPLS statistical analyses.

Sat, 20/06/2015 - 13:08
Related Articles Analysis of the human adult urinary metabolome variations with age, body mass index and gender by implementing a comprehensive workflow for univariate and OPLS statistical analyses. J Proteome Res. 2015 Jun 19; Authors: Thévenot EA, Roux A, Xu Y, Ezan E, Junot C Abstract Urine metabolomics is widely used for biomarker research in the fields of medicine and toxicology. As a consequence, characterization of the variations of the urine metabolome in basal conditions becomes critical in order to avoid confounding effects in cohort studies. Such physiological information is however very scarce in the literature and in metabolomics databases so far. Here we studied the influence of age, body mass index (BMI) and gender on metabolite concentrations in a large cohort of 183 adults by using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). We implemented a comprehensive statistical workflow for univariate hypothesis testing and modeling by orthogonal partial least-squares (OPLS), which we made available to the metabolomics community within the online Workflow4Metabolomics.org resource. We found 108 urine metabolites displaying concentration variations with either age, BMI, or gender, by integrating the results from univariate p-values and multivariate variable importance in projection (VIP). Several metabolite clusters were further evidenced by correlation analysis, and allowed stratification of the cohort. In conclusion, our study highlights the impact of gender and age on the urinary metabolome, and thus indicates that these factors should be taken into account for the design of metabolomics studies. PMID: 26088811 [PubMed - as supplied by publisher]

Proteomic and metabonomic biomarkers for hepatocellular carcinoma: a comprehensive review.

Sat, 20/06/2015 - 13:08
Related Articles Proteomic and metabonomic biomarkers for hepatocellular carcinoma: a comprehensive review. Br J Cancer. 2015 Mar 31;112(7):1141-56 Authors: Kimhofer T, Fye H, Taylor-Robinson S, Thursz M, Holmes E Abstract Hepatocellular carcinoma (HCC) ranks third in overall global cancer-related mortality. Symptomatic presentation often means advanced disease where potentially curative treatment options become very limited. Numerous international guidelines propose the routine monitoring of those with the highest risk factors for the condition in order to diagnose potential tumourigenesis early. To aid this, the fields of metabonomic- and proteomic-based biomarker discovery have applied advanced tools to identify early changes in protein and metabolite expression in HCC patients vs controls. With robust validation, it is anticipated that from these candidates will rise a high-performance non-invasive test able to diagnose early HCC and related conditions. This review gathers the numerous markers proposed by studies using mass spectrometry and proton nuclear magnetic resonance spectroscopy and evaluates areas of consistency as well as discordance. PMID: 25826224 [PubMed - indexed for MEDLINE]

Development of personalized functional foods needs metabolic profiling.

Sat, 20/06/2015 - 13:08
Related Articles Development of personalized functional foods needs metabolic profiling. Curr Opin Clin Nutr Metab Care. 2014 Nov;17(6):567-73 Authors: Claus SP Abstract PURPOSE OF REVIEW: There is growing interest in applying metabolic profiling technologies to food science as this approach is now embedded into the foodomics toolbox. This review aims at exploring how metabolic profiling can be applied to the development of functional foods. RECENT FINDINGS: One of the biggest challenges of modern nutrition is to propose a healthy diet to populations worldwide that must suit high inter-individual variability driven by complex gene-nutrient-environment interactions. Although a number of functional foods are now proposed in support of a healthy diet, a one-size-fits-all approach to nutrition is inappropriate and new personalized functional foods are necessary. Metabolic profiling technologies can assist at various levels of the development of functional foods, from screening for food composition to identification of new biomarkers of food intake to support diet intervention and epidemiological studies. SUMMARY: Modern 'omics' technologies, including metabolic profiling, will support the development of new personalized functional foods of high relevance to 21st century medical challenges, such as controlling the worldwide spread of metabolic disorders and ensuring healthy ageing. PMID: 25137506 [PubMed - indexed for MEDLINE]

Sorting signal targeting mRNA into hepatic extracellular vesicles.

Sat, 20/06/2015 - 13:08
Related Articles Sorting signal targeting mRNA into hepatic extracellular vesicles. RNA Biol. 2014;11(7):836-44 Authors: Szostak N, Royo F, Rybarczyk A, Szachniuk M, Blazewicz J, del Sol A, Falcon-Perez JM Abstract Intercellular communication mediated by extracellular vesicles has proved to play an important role in normal and pathological scenarios. However not too much information about the sorting mechanisms involved in loading the vesicles is available. Recently, our group has characterized the mRNA content of vesicles released by hepatic cellular systems, showing that a set of transcripts was particularly enriched in the vesicles in comparison with their intracellular abundance. In the current work, based on in silico bioinformatics tools, we have mapped a novel sequence of 12 nucleotides C[TA]G[GC][AGT]G[CT]C[AT]GG[GA], which is significantly enriched in the set of mRNAs that accumulate in extracellular vesicles. By including a 3'-UTR containing this sequence in a luciferase mRNA reporter, we have shown that in a hepatic cellular system this reporter mRNA was incorporated into extracellular vesicles. This study identifies a sorting signal in mRNAs that is involved in their enrichment in EVs, within a hepatic non-tumoral cellular model. PMID: 24921245 [PubMed - indexed for MEDLINE]

A protective lipidomic biosignature associated with a balanced omega-6/omega-3 ratio in fat-1 transgenic mice.

Sat, 20/06/2015 - 13:08
Related Articles A protective lipidomic biosignature associated with a balanced omega-6/omega-3 ratio in fat-1 transgenic mice. PLoS One. 2014;9(4):e96221 Authors: Astarita G, McKenzie JH, Wang B, Strassburg K, Doneanu A, Johnson J, Baker A, Hankemeier T, Murphy J, Vreeken RJ, Langridge J, Kang JX Abstract A balanced omega-6/omega-3 polyunsaturated fatty acid (PUFA) ratio has been linked to health benefits and the prevention of many chronic diseases. Current dietary intervention studies with different sources of omega-3 fatty acids (omega-3) lack appropriate control diets and carry many other confounding factors derived from genetic and environmental variability. In our study, we used the fat-1 transgenic mouse model as a proxy for long-term omega-3 supplementation to determine, in a well-controlled manner, the molecular phenotype associated with a balanced omega-6/omega-3 ratio. The fat-1 mouse can convert omega-6 to omega-3 PUFAs, which protect against a wide variety of diseases including chronic inflammatory diseases and cancer. Both wild-type (WT) and fat-1 mice were subjected to an identical diet containing 10% corn oil, which has a high omega-6 content similar to that of the Western diet, for a six-month duration. We used a multi-platform lipidomic approach to compare the plasma lipidome between fat-1 and WT mice. In fat-1 mice, an unbiased profiling showed a significant increase in the levels of unesterified eicosapentaenoic acid (EPA), EPA-containing cholesteryl ester, and omega-3 lysophosphospholipids. The increase in omega-3 lipids is accompanied by a significant reduction in omega-6 unesterified docosapentaenoic acid (omega-6 DPA) and DPA-containing cholesteryl ester as well as omega-6 phospholipids and triacylglycerides. Targeted lipidomics profiling highlighted a remarkable increase in EPA-derived diols and epoxides formed via the cytochrome P450 (CYP450) pathway in the plasma of fat-1 mice compared with WT mice. Integration of the results of untargeted and targeted analyses has identified a lipidomic biosignature that may underlie the healthful phenotype associated with a balanced omega-6/omega-3 ratio, and can potentially be used as a circulating biomarker for monitoring the health status and the efficacy of omega-3 intervention in humans. PMID: 24760204 [PubMed - indexed for MEDLINE]

Prospective evaluation of potential toxicity of repeated doses of Thymus vulgaris L. extracts in rats by means of clinical chemistry, histopathology and NMR-based metabonomic approach.

Sat, 20/06/2015 - 13:08
Related Articles Prospective evaluation of potential toxicity of repeated doses of Thymus vulgaris L. extracts in rats by means of clinical chemistry, histopathology and NMR-based metabonomic approach. Drug Test Anal. 2014 Oct;6(10):1069-75 Authors: Benourad F, Kahvecioglu Z, Youcef-Benkada M, Colet JM Abstract In the field of natural extracts, research generally focuses on the study of their biological activities for food, cosmetic, or pharmacological purposes. The evaluation of their adverse effects is often overlooked. In this study, the extracts of Thymus vulgaris L. were obtained by two different extraction methods. Intraperitoneal injections of both extracts were given daily for four days to male Wistar Han rats, at two different doses for each extract. The evaluation of the potential toxic effects included histopathological examination of liver, kidney, and lung tissues, as well as serum biochemistry of liver and kidney parameters, and (1)H-NMR-based metabonomic profiles of urine. The results showed that no histopathological changes were observed in the liver and kidney in rats treated with both extracts of thyme. Serum biochemical investigations revealed significant increases in blood urea nitrogen, creatinine, and uric acid in animals treated with polyphenolic extract at both doses. In these latter groups, metabonomic analysis revealed alterations in a number of urine metabolites involved in the energy metabolism in liver mitochondria. Indeed, the results showed alterations of glycolysis, Krebs cycle, and β-oxidative pathways as evidenced by increases in lactate and ketone bodies, and decreases in citrate, α-ketoglutarate, creatinine, hippurate, dimethylglycine, and dimethyalanine. In conclusion, this work showed that i.p. injection of repeated doses of thyme extracts causes some disturbances of intermediary metabolism in rats. The metabonomic study revealed interesting data which could be further used to determine the cellular pathways affected by such treatments. PMID: 24574060 [PubMed - indexed for MEDLINE]

metabolomics; +21 new citations

Fri, 19/06/2015 - 12:33
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 2015/06/19PubMed 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.

Untargeted Metabolomics Reveals Predominant Alterations in Lipid Metabolism Following Light Exposure in Broccoli Sprouts.

Thu, 18/06/2015 - 14:51
Untargeted Metabolomics Reveals Predominant Alterations in Lipid Metabolism Following Light Exposure in Broccoli Sprouts. Int J Mol Sci. 2015;16(6):13678-13691 Authors: Maldini M, Natella F, Baima S, Morelli G, Scaccini C, Langridge J, Astarita G Abstract The consumption of vegetables belonging to the family Brassicaceae (e.g., broccoli and cauliflower) is linked to a reduced incidence of cancer and cardiovascular diseases. The molecular composition of such plants is strongly affected by growing conditions. Here we developed an unbiased metabolomics approach to investigate the effect of light and dark exposure on the metabolome of broccoli sprouts and we applied such an approach to provide a bird's-eye view of the overall metabolic response after light exposure. Broccoli seeds were germinated and grown hydroponically for five days in total darkness or with a light/dark photoperiod (16 h light/8 h dark cycle). We used an ultra-performance liquid-chromatography system coupled to an ion-mobility, time-of-flight mass spectrometer to profile the large array of metabolites present in the sprouts. Differences at the metabolite level between groups were analyzed using multivariate statistical analyses, including principal component analysis and correlation analysis. Altered metabolites were identified by searching publicly available and in-house databases. Metabolite pathway analyses were used to support the identification of subtle but significant changes among groups of related metabolites that may have gone unnoticed with conventional approaches. Besides the chlorophyll pathway, light exposure activated the biosynthesis and metabolism of sterol lipids, prenol lipids, and polyunsaturated lipids, which are essential for the photosynthetic machinery. Our results also revealed that light exposure increased the levels of polyketides, including flavonoids, and oxylipins, which play essential roles in the plant's developmental processes and defense mechanism against herbivores. This study highlights the significant contribution of light exposure to the ultimate metabolic phenotype, which might affect the cellular physiology and nutritional value of broccoli sprouts. Furthermore, this study highlights the potential of an unbiased omics approach for the comprehensive study of the metabolism. PMID: 26084047 [PubMed - as supplied by publisher]

Necrosis: Linking the Inflammasome to Inflammation.

Thu, 18/06/2015 - 14:51
Necrosis: Linking the Inflammasome to Inflammation. Cell Rep. 2015 Jun 16;11(10):1501-1502 Authors: Galluzzi L, Bravo-San Pedro JM, Kroemer G Abstract In this issue of Cell Reports, Cullen et al. demonstrate that the release of mature interleukin-1β relies on necrotic plasma membrane permeabilization. Thus, caspases may have evolved to modulate the inflammatory potential of cell death, not to execute it. PMID: 26082972 [PubMed - as supplied by publisher]

Corrigendum: "Combinatorial Strategies for the Induction of Immunogenic Cell Death".

Thu, 18/06/2015 - 14:51
Corrigendum: "Combinatorial Strategies for the Induction of Immunogenic Cell Death". Front Immunol. 2015;6:275 Authors: Bezu L, Gomes-da-Silva LC, Dewitte H, Breckpot K, Fucikova J, Spisek R, Galluzzi L, Kepp O, Kroemer G Abstract [This corrects the article on p. 187 in vol. 6, PMID: 25964783.]. PMID: 26082782 [PubMed - as supplied by publisher]

Differential CO2 effect on primary carbon metabolism of flag leaves in durum wheat (Triticum durum Desf.).

Thu, 18/06/2015 - 14:51
Differential CO2 effect on primary carbon metabolism of flag leaves in durum wheat (Triticum durum Desf.). Plant Cell Environ. 2015 Jun 17; Authors: Aranjuelo I, Erice G, Sanz-Sáez A, Abadie C, Gilard F, Gil E, Avice JC, Staudinger C, Wienkoop S, Araus JL, Bourguignon J, Irigoyen JJ, Tcherkez G Abstract C sink/source balance and N assimilation have been identified as target processes conditioning crop responsiveness to elevated CO2 . However, little is known about phenology-driven modifications of C and N primary metabolism at elevated CO2 in cereals such as wheat. Here, we examined the differential effect of elevated CO2 at two development stages (onset of flowering, onset of grain filling) in durum wheat (Triticum durum, var. Sula) using physiological measurements (photosynthesis, isotopes), metabolomics, proteomics and (15) N-labelling. Our results show that growth at elevated CO2 was accompanied by photosynthetic acclimation through a lower internal (mesophyll) conductance but no significant effect on Rubisco content, maximal carboxylation or electron transfer. Growth at elevated CO2 altered photosynthate export and tended to accelerate leaf N remobilization, which was visible for several proteins and amino acids, as well as lysine degradation metabolism. However, grain biomass produced at elevated CO2 was larger and less N-rich, suggesting that nitrogen use efficiency rather than photosynthesis is an important target for improvement, even in good CO2 -responsive cultivars. PMID: 26081746 [PubMed - as supplied by publisher]

Distribution and biomarker of carbon-14 labeled fullerene C60 ([(14) C(U)]C60 ) in pregnant and lactating rats and their offspring after maternal intravenous exposure.

Thu, 18/06/2015 - 14:51
Distribution and biomarker of carbon-14 labeled fullerene C60 ([(14) C(U)]C60 ) in pregnant and lactating rats and their offspring after maternal intravenous exposure. J Appl Toxicol. 2015 Jun 17; Authors: Snyder RW, Fennell TR, Wingard CJ, Mortensen NP, Holland NA, Shannahan JH, Pathmasiri W, Lewin AH, Sumner SC Abstract A comprehensive distribution study was conducted in pregnant and lactating rats exposed to a suspension of uniformly carbon-14 labeled C60 ([(14) C(U)]C60 ). Rats were administered [(14) C(U)]C60 (~0.2 mg [(14) C(U)]C60 kg(-1) body weight) or 5% polyvinylpyrrolidone (PVP)-saline vehicle via a single tail vein injection. Pregnant rats were injected on gestation day (GD) 11 (terminated with fetuses after either 24 h or 8 days), GD15 (terminated after 24 h or 4 days), or GD18 (terminated after 24 h). Lactating rats were injected on postnatal day 8 and terminated after 24 h, 3 or 11 days. The distribution of radioactivity in pregnant dams was influenced by both the state of pregnancy and time of termination after exposure. The percentage of recovered radioactivity in pregnant and lactating rats was highest in the liver and lungs. Radioactivity was quantitated in over 20 tissues. Radioactivity was found in the placenta and in fetuses of pregnant dams, and in the milk of lactating rats and in pups. Elimination of radioactivity was < 2% in urine and feces at each time point. Radioactivity remained in blood circulation up to 11 days after [(14) C(U)]C60 exposure. Biomarkers of inflammation, cardiovascular injury and oxidative stress were measured to study the biological impacts of [(14) C(U)]C60 exposure. Oxidative stress was elevated in female pups of exposed dams. Metabolomics analysis of urine showed that [(14) C(U)]C60 exposure to pregnant rats impacted the pathways of vitamin B, regulation of lipid and sugar metabolism and aminoacyl-tRNA biosynthesis. This study demonstrated that [(14) C(U)]C60 crosses the placenta at all stages of pregnancy examined, and is transferred to pups via milk. Copyright © 2015 John Wiley & Sons, Ltd. PMID: 26081520 [PubMed - as supplied by publisher]

NMR based serum metabolomics discriminates Takayasu Arteritis from Healthy Individuals: A proof of principle study.

Thu, 18/06/2015 - 14:51
NMR based serum metabolomics discriminates Takayasu Arteritis from Healthy Individuals: A proof of principle study. J Proteome Res. 2015 Jun 17; Authors: Guleria A, Misra DP, Rawat A, Dubey D, Khetrapal CL, Bacon P, Misra R, Kumar D Abstract Takayasu Arteritis (TA) is a debilitating, systemic disease which involves the aorta and large arteries in a chronic inflammatory process leading to vessel stenosis. Initially, the disease remains clinically silent (or remains undetected) until the patients present with vascular occlusion. Therefore, new methods for appropriate and timely diagnosis of TA cases are needed to start proper therapy on time and also to monitor the patient's response to the given treatment. In this context, NMR-based serum metabolomic profiling has been explored in this proof of principle study for the first time to determine characteristic metabolites that could potentially be helpful for diagnosis and prognosis of TA. Serum metabolic profiling of TA patients (n = 29) and healthy controls (n = 30) was performed using 1D 1H NMR spectroscopy and possible biomarker metabolites were identified. Using projection to least squares discriminant analysis, we could distinguish TA patients from healthy controls. Compared to healthy controls, the TA patients had (a) increased serum levels of choline metabolites, LDL cholesterol, N-acetyl glycoproteins (NAGs), and glucose and (b) decreased serum levels of lactate, lipids, HDL cholesterol, glucogenic amino acids. The results of this study are preliminary and need to be confirmed in a prospective study. PMID: 26081138 [PubMed - as supplied by publisher]

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