9 research outputs found
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Metabolomics Reveals the Molecular Mechanisms of Copper Induced Cucumber Leaf ( Cucumis sativus) Senescence.
Excess copper may disturb plant photosynthesis and induce leaf senescence. The underlying toxicity mechanism is not well understood. Here, 3-week-old cucumber plants were foliar exposed to different copper concentrations (10, 100, and 500 mg/L) for a final dose of 0.21, 2.1, and 10 mg/plant, using CuSO4 as the Cu ion source for 7 days, three times per day. Metabolomics quantified 149 primary and 79 secondary metabolites. A number of intermediates of the tricarboxylic acid (TCA) cycle were significantly down-regulated 1.4-2.4 fold, indicating a perturbed carbohydrate metabolism. Ascorbate and aldarate metabolism and shikimate-phenylpropanoid biosynthesis (antioxidant and defense related pathways) were perturbed by excess copper. These metabolic responses occur even at the lowest copper dose considered although no phenotype changes were observed at this dose. High copper dose resulted in a 2-fold increase in phytol, a degradation product of chlorophyll. Polyphenol metabolomics revealed that some flavonoids were down-regulated, while the nonflavonoid 4-hydroxycinnamic acid and trans-2-hydroxycinnamic acid were significantly up-regulated 4- and 26-fold compared to the control. This study enhances current understanding of copper toxicity to plants and demonstrates that metabolomics profiling provides a more comprehensive view of plant responses to stressors, which can be applied to other plant species and contaminants
Recommended from our members
Metabolomics Reveals the Molecular Mechanisms of Copper Induced Cucumber Leaf ( Cucumis sativus) Senescence.
Excess copper may disturb plant photosynthesis and induce leaf senescence. The underlying toxicity mechanism is not well understood. Here, 3-week-old cucumber plants were foliar exposed to different copper concentrations (10, 100, and 500 mg/L) for a final dose of 0.21, 2.1, and 10 mg/plant, using CuSO4 as the Cu ion source for 7 days, three times per day. Metabolomics quantified 149 primary and 79 secondary metabolites. A number of intermediates of the tricarboxylic acid (TCA) cycle were significantly down-regulated 1.4-2.4 fold, indicating a perturbed carbohydrate metabolism. Ascorbate and aldarate metabolism and shikimate-phenylpropanoid biosynthesis (antioxidant and defense related pathways) were perturbed by excess copper. These metabolic responses occur even at the lowest copper dose considered although no phenotype changes were observed at this dose. High copper dose resulted in a 2-fold increase in phytol, a degradation product of chlorophyll. Polyphenol metabolomics revealed that some flavonoids were down-regulated, while the nonflavonoid 4-hydroxycinnamic acid and trans-2-hydroxycinnamic acid were significantly up-regulated 4- and 26-fold compared to the control. This study enhances current understanding of copper toxicity to plants and demonstrates that metabolomics profiling provides a more comprehensive view of plant responses to stressors, which can be applied to other plant species and contaminants
Metabolomics Reveals the Molecular Mechanisms of Copper Induced Cucumber Leaf (<i>Cucumis sativus</i>) Senescence
Excess copper may disturb plant photosynthesis
and induce leaf
senescence. The underlying toxicity mechanism is not well understood.
Here, 3-week-old cucumber plants were foliar exposed to different
copper concentrations (10, 100, and 500 mg/L) for a final dose of
0.21, 2.1, and 10 mg/plant, using CuSO<sub>4</sub> as the Cu ion source
for 7 days, three times per day. Metabolomics quantified 149 primary
and 79 secondary metabolites. A number of intermediates of the tricarboxylic
acid (TCA) cycle were significantly down-regulated 1.4â2.4
fold, indicating a perturbed carbohydrate metabolism. Ascorbate and
aldarate metabolism and shikimate-phenylpropanoid biosynthesis (antioxidant
and defense related pathways) were perturbed by excess copper. These
metabolic responses occur even at the lowest copper dose considered
although no phenotype changes were observed at this dose. High copper
dose resulted in a 2-fold increase in phytol, a degradation product
of chlorophyll. Polyphenol metabolomics revealed that some flavonoids
were down-regulated, while the nonflavonoid 4-hydroxycinnamic acid
and <i>trans</i>-2-hydroxycinnamic acid were significantly
up-regulated 4- and 26-fold compared to the control. This study enhances
current understanding of copper toxicity to plants and demonstrates
that metabolomics profiling provides a more comprehensive view of
plant responses to stressors, which can be applied to other plant
species and contaminants
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Mass Spectral Feature List Optimizer (MS-FLO): A Tool To Minimize False Positive Peak Reports in Untargeted Liquid ChromatographyâMass Spectroscopy (LC-MS) Data Processing
Untargeted
metabolomics by liquid chromatographyâmass spectrometry
generates data-rich chromatograms in the form of <i>m</i>/<i>z</i>-retention time features. Managing such datasets
is a bottleneck. Many popular data processing tools, including XCMS-online
and MZmine2, yield numerous false-positive peak detections. Flagging
and removing such false peaks manually is a time-consuming task and
prone to human error. We present a web application, Mass Spectral
Feature List Optimizer (MS-FLO), to improve the quality of feature
lists after initial processing to expedite the process of data curation.
The tool utilizes retention time alignments, accurate mass tolerances,
Pearsonâs correlation analysis, and peak height similarity
to identify ion adducts, duplicate peak reports, and isotopic features
of the main monoisotopic metabolites. Removing such erroneous peaks
reduces the overall number of metabolites in data reports and improves
the quality of subsequent statistical investigations. To demonstrate
the effectiveness of MS-FLO, we processed 28 biological studies and
uploaded raw and results data to the Metabolomics Workbench website
(www.metabolomicsworkbench.org), encompassing 1481 chromatograms produced by two different data
processing programs used in-house (MZmine2 and later MS-DIAL). Post-processing
of datasets with MS-FLO yielded a 7.8% automated reduction of total
peak features and flagged an additional 7.9% of features, per dataset,
for review by the user. When manually curated, 87% of these additional
flagged features were verified false positives. MS-FLO is an open
source web application that is freely available for use at http://msflo.fiehnlab.ucdavis.edu
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Primed mesenchymal stem cells package exosomes with metabolites associated with immunomodulation.
Mesenchymal stem cell (MSC) based therapies are currently being evaluated as a putative therapeutic in numerous human clinical trials. Recent reports have established that exosomes mediate much of the therapeutic properties of MSCs. Exosomes are nanovesicles which mediate intercellular communication, transmitting signals between cells which regulate a diverse range of biological processes. MSC-derived exosomes are packaged with numerous types of proteins and RNAs, however, their metabolomic and lipidomic profiles to date have not been well characterized. We previously reported that MSCs, in response to priming culture conditions that mimic the in vivo microenvironmental niche, substantially modulate cellular signaling and significantly increase the secretion of exosomes. Here we report that MSCs exposed to such priming conditions undergo glycolytic reprogramming, which homogenizes MSCs' metabolomic profile. In addition, we establish that exosomes derive from primed MSCs are packaged with numerous metabolites that have been directly associated with immunomodulation, including M2 macrophage polarization and regulatory T lymphocyte induction
An Isoprene Lipid-Binding Protein Promotes Eukaryotic Coenzyme Q Biosynthesis
The biosynthesis of coenzyme Q presents a paradigm for how cells surmount hydrophobic barriers in lipid biology. In eukaryotes, CoQ precursors-among nature's most hydrophobic molecules-must somehow be presented to a series of enzymes peripherally associated with the mitochondrial inner membrane. Here, we reveal that this process relies on custom lipid-binding properties of COQ9. We show that COQ9 repurposes the bacterial TetR fold to bind aromatic isoprenes with high specificity, including CoQ intermediates that likely reside entirely within the bilayer. We reveal a process by which COQ9 associates with cardiolipin-rich membranes and warps the membrane surface to access this cargo. Finally, we identify a molecular interface between COQ9 and the hydroxylase COQ7, motivating a model whereby COQ9 presents intermediates directly to CoQ enzymes. Overall, our results provide a mechanism for how a lipid-binding protein might access, select, and deliver specific cargo from a membrane to promote biosynthesis
Functional Microbiomics Reveals Alterations of the Gut Microbiome and Host CoâMetabolism in Patients With Alcoholic Hepatitis
Alcohol-related liver disease is a major public health burden, and the gut microbiota is an important contributor to disease pathogenesis. The aim of the present study is to characterize functional alterations of the gut microbiota and test their performance for short-term mortality prediction in patients with alcoholic hepatitis. We integrated shotgun metagenomics with untargeted metabolomics to investigate functional alterations of the gut microbiota and host co-metabolism in a multicenter cohort of patients with alcoholic hepatitis. Profound changes were found in the gut microbial composition, functional metagenome, serum, and fecal metabolomes in patients with alcoholic hepatitis compared with nonalcoholic controls. We demonstrate that in comparison with single omics alone, the performance to predict 30-day mortality was improved when combining microbial pathways with respective serum metabolites in patients with alcoholic hepatitis. The area under the receiver operating curve was higher than 0.85 for the tryptophan, isoleucine, and methionine pathways as predictors for 30-day mortality, but achieved 0.989 for using the urea cycle pathway in combination with serum urea, with a bias-corrected prediction error of 0.083 when using leave-one-out cross validation. Conclusion: Our study reveals changes in key microbial metabolic pathways associated with disease severity that predict short-term mortality in our cohort of patients with alcoholic hepatitis
Functional Microbiomics Reveals Alterations of the Gut Microbiome and Host CoâMetabolism in Patients With Alcoholic Hepatitis
Alcohol-related liver disease is a major public health burden, and the gut microbiota is an important contributor to disease pathogenesis. The aim of the present study is to characterize functional alterations of the gut microbiota and test their performance for short-term mortality prediction in patients with alcoholic hepatitis. We integrated shotgun metagenomics with untargeted metabolomics to investigate functional alterations of the gut microbiota and host co-metabolism in a multicenter cohort of patients with alcoholic hepatitis. Profound changes were found in the gut microbial composition, functional metagenome, serum, and fecal metabolomes in patients with alcoholic hepatitis compared with nonalcoholic controls. We demonstrate that in comparison with single omics alone, the performance to predict 30-day mortality was improved when combining microbial pathways with respective serum metabolites in patients with alcoholic hepatitis. The area under the receiver operating curve was higher than 0.85 for the tryptophan, isoleucine, and methionine pathways as predictors for 30-day mortality, but achieved 0.989 for using the urea cycle pathway in combination with serum urea, with a bias-corrected prediction error of 0.083 when using leave-one-out cross validation. Conclusion: Our study reveals changes in key microbial metabolic pathways associated with disease severity that predict short-term mortality in our cohort of patients with alcoholic hepatitis