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

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 4 min 28 sec ago

CRISPR/Cas9-mediated efficient targeted mutagenesis of RAS in Salvia miltiorrhiza.

Fri, 09/02/2018 - 13:50
CRISPR/Cas9-mediated efficient targeted mutagenesis of RAS in Salvia miltiorrhiza. Phytochemistry. 2018 Jan 30;148:63-70 Authors: Zhou Z, Tan H, Li Q, Chen J, Gao S, Wang Y, Chen W, Zhang L Abstract The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 (CRISPR-associated) system is a powerful genome editing tool that has been used in many species. In this study, we focused on the phenolic acid metabolic pathway in the traditional Chinese medicinal herb Salvia miltiorrhiza, using the CRISPR/Cas9 system to edit the rosmarinic acid synthase gene (SmRAS) in the water-soluble phenolic acid biosynthetic pathway. The single guide RNA (sgRNA) was designed to precisely edit the most important SmRAS gene, which was selected from 11 family members through a bioinformatics analysis. The sequencing results showed that the genomes of 50% of the transgenic regenerated hairy roots had been successfully edited. Five biallelic mutants, two heterozygous mutants and one homozygous mutant were obtained from 16 independent transgenic hairy root lines when the sgRNA was driven by the Arabidopsis U6 promoter, while no mutants were obtained from 13 independent transgenic hairy root lines when the sgRNA was driven by the rice U3 promoter. Subsequently, expression and metabolomics analysis showed that the contents of phenolic acids, including rosmarinic acid (RA) and lithospermic acid B, and the RAS expression level were decreased in the successfully edited hairy root lines, particularly in the homozygous mutants. In addition, the level of the RA precursor 3,4-dihydroxyphenyllactic acid clearly increased. These results indicated that the CRISPR/Cas9 system can be utilized to identify important genes in a gene family with the assistance of bioinformatics analysis and that this new technology is an efficient and specific tool for genome editing in S. miltiorrhiza. This new system presents a promising potential method to regulate plant metabolic networks and improve the quality of traditional Chinese medicinal herbs. PMID: 29421512 [PubMed - as supplied by publisher]

Lipids, Lipoproteins, and Metabolites and Risk of Myocardial Infarction and Stroke.

Fri, 09/02/2018 - 13:50
Lipids, Lipoproteins, and Metabolites and Risk of Myocardial Infarction and Stroke. J Am Coll Cardiol. 2018 Feb 13;71(6):620-632 Authors: Holmes MV, Millwood IY, Kartsonaki C, Hill MR, Bennett DA, Boxall R, Guo Y, Xu X, Bian Z, Hu R, Walters RG, Chen J, Ala-Korpela M, Parish S, Clarke RJ, Peto R, Collins R, Li L, Chen Z, China Kadoorie Biobank Collaborative Group Abstract BACKGROUND: Blood lipids are established risk factors for myocardial infarction (MI), but uncertainty persists about the relevance of lipids, lipoprotein particles, and circulating metabolites for MI and stroke subtypes. OBJECTIVES: This study sought to investigate the associations of plasma metabolic markers with risks of incident MI, ischemic stroke (IS), and intracerebral hemorrhage (ICH). METHODS: In a nested case-control study (912 MI, 1,146 IS, and 1,138 ICH cases, and 1,466 common control subjects) 30 to 79 years of age in China Kadoorie Biobank, nuclear magnetic resonance spectroscopy measured 225 metabolic markers in baseline plasma samples. Logistic regression was used to estimate adjusted odds ratios (ORs) for a 1-SD higher metabolic marker. RESULTS: Very low-, intermediate-, and low-density lipoprotein particles were positively associated with MI and IS. High-density lipoprotein (HDL) particles were inversely associated with MI apart from small HDL. In contrast, no lipoprotein particles were associated with ICH. Cholesterol in large HDL was inversely associated with MI and IS (OR: 0.79 and 0.88, respectively), whereas cholesterol in small HDL was not (OR: 0.99 and 1.06, respectively). Triglycerides within all lipoproteins, including most HDL particles, were positively associated with MI, with a similar pattern for IS. Glycoprotein acetyls, ketone bodies, glucose, and docosahexaenoic acid were associated with all 3 diseases. The 225 metabolic markers showed concordant associations between MI and IS, but not with ICH. CONCLUSIONS: Lipoproteins and lipids showed similar associations with MI and IS, but not with ICH. Within HDL particles, cholesterol concentrations were inversely associated, whereas triglyceride concentrations were positively associated with MI. Glycoprotein acetyls and several non-lipid-related metabolites associated with all 3 diseases. PMID: 29420958 [PubMed - in process]

High-pressure photon ionization time-of-flight mass spectrometry combined with dynamic purge-injection for rapid analysis of volatile metabolites in urine.

Fri, 09/02/2018 - 13:50
High-pressure photon ionization time-of-flight mass spectrometry combined with dynamic purge-injection for rapid analysis of volatile metabolites in urine. Anal Chim Acta. 2018 May 30;1008:74-81 Authors: Wang Y, Hua L, Jiang J, Xie Y, Hou K, Li Q, Wu C, Li H Abstract Small molecule metabolites are widely used as biomarkers in the research field of metabolomics for disease diagnosis and exposure assessment. As a readily available biofluid containing plenty of volatile organic metabolites (VOMs), urine is ideal for non-invasive metabolomic analysis; however, there is still lack of rapid analysis method for VOMs in urine. Here we report a kind of rapid method for urine analysis by employing high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS) combined with dynamic purge-injection. Various types of metabolites, such as ketones, alcohols, acids, sulfides, pyrroles and amines were detected directly by simple acidification or alkalization of urines. It is noteworthy that nitrogen-containing compounds, especially polar amines, could be ultrasensitively measured without any derivatization. The analytical capability of the direct HPPI-MS technique was demonstrated by analyzing five valuable metabolites, i.e., toluene, 2,5-dimethylpyrrole, trimethlyamine, styrene, and p-xylene, which exhibited relatively low limits of detection, wide linear range and satisfactory repeatability. Being highly sensitive and humidity-friendly, the whole analytical procedure is easily operated in less than 6 min. Interestingly, a new biomarker 2,5-dimethylpyrrole was exclusively found in the smoker's urine sample besides toluene. The work presents a novel tool for rapid nontarget disease biomarkers screening or target monitoring of specific compounds through the investigation of volatile metabolites in urine. PMID: 29420946 [PubMed - in process]

A metabolomic map of Zellweger spectrum disorders reveals novel disease biomarkers.

Fri, 09/02/2018 - 13:50
A metabolomic map of Zellweger spectrum disorders reveals novel disease biomarkers. Genet Med. 2018 Feb 08;: Authors: Wangler MF, Hubert L, Donti TR, Ventura MJ, Miller MJ, Braverman N, Gawron K, Bose M, Moser AB, Jones RO, Rizzo WB, Sutton VR, Sun Q, Kennedy AD, Elsea SH Abstract PurposePeroxisome biogenesis disorders-Zellweger spectrum disorders (PBD-ZSD) are metabolic diseases with multisystem manifestations. Individuals with PBD-ZSD exhibit impaired peroxisomal biochemical functions and have abnormal levels of peroxisomal metabolites, but the broader metabolic impact of peroxisomal dysfunction and the utility of metabolomic methods is unknown.MethodsWe studied 19 individuals with clinically and molecularly characterized PBD-ZSD. We performed both quantitative peroxisomal biochemical diagnostic studies in parallel with untargeted small molecule metabolomic profiling in plasma samples with detection of >650 named compounds.ResultsThe cohort represented intermediate to mild PBD-ZSD subjects with peroxisomal biochemical alterations on targeted analysis. Untargeted metabolomic profiling of these samples revealed elevations in pipecolic acid and long-chain lysophosphatidylcholines, as well as an unanticipated reduction in multiple sphingomyelin species. These sphingomyelin reductions observed were consistent across the PBD-ZSD samples and were rare in a population of >1,000 clinical samples. Interestingly, the pattern or "PBD-ZSD metabolome" was more pronounced in younger subjects suggesting studies earlier in life reveal larger biochemical changes.ConclusionUntargeted metabolomics is effective in detecting mild to intermediate cases of PBD-ZSD. Surprisingly, dramatic reductions in plasma sphingomyelin are a consistent feature of the PBD-ZSD metabolome. The use of metabolomics in PBD-ZSD can provide insight into novel biomarkers of disease.GENETICS in MEDICINE advance online publication, 8 February 2018; doi:10.1038/gim.2017.262. PMID: 29419819 [PubMed - as supplied by publisher]

Untargeted metabolomics confirms and extends the understanding of the impact of aminoimidazole carboxamide ribotide (AICAR) in the metabolic network of Salmonella enterica.

Fri, 09/02/2018 - 13:50
Untargeted metabolomics confirms and extends the understanding of the impact of aminoimidazole carboxamide ribotide (AICAR) in the metabolic network of Salmonella enterica. Microb Cell. 2017 Nov 22;5(2):74-87 Authors: Bazurto JV, Dearth SP, Tague ED, Campagna SR, Downs DM Abstract In Salmonella enterica, aminoimidazole carboxamide ribotide (AICAR) is a purine biosynthetic intermediate and a substrate of the AICAR transformylase/IMP cyclohydrolase (PurH) enzyme. When purH is eliminated in an otherwise wild-type strain, AICAR accumulates and indirectly inhibits synthesis of the essential coenzyme thiamine pyrophosphate (TPP). In this study, untargeted metabolomics approaches were used to i) corroborate previously defined metabolite changes, ii) define the global consequences of AICAR accumulation and iii) investigate the metabolic effects of mutations that restore thiamine prototrophy to a purH mutant. The data showed that AICAR accumulation led to an increase in the global regulator cyclic AMP (cAMP) and that disrupting central carbon metabolism could decrease AICAR and/or cAMP to restore thiamine synthesis. A mutant (icc) blocked in cAMP degradation that accumulated cAMP but had wild-type levels of AICAR was used to identify changes in the purH metabolome that were a direct result of elevated cAMP. Data herein describe the use of metabolomics to identify the metabolic state of mutant strains and probe the underlying mechanisms used by AICAR to inhibit thiamine synthesis. The results obtained provide a cautionary tale of using metabolite concentrations as the only data to define the physiological state of a bacterial cell. PMID: 29417056 [PubMed]

Metabolomic alterations in invasive ductal carcinoma of breast: A comprehensive metabolomic study using tissue and serum samples.

Fri, 09/02/2018 - 13:50
Metabolomic alterations in invasive ductal carcinoma of breast: A comprehensive metabolomic study using tissue and serum samples. Oncotarget. 2018 Jan 05;9(2):2678-2696 Authors: More TH, RoyChoudhury S, Christie J, Taunk K, Mane A, Santra MK, Chaudhury K, Rapole S Abstract Invasive ductal carcinoma (IDC) is the most common type of breast cancer and the leading cause of breast cancer related mortality. In the present study, metabolomic profiles of 72 tissue samples and 146 serum samples were analysed using targeted liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM/MS) and untargeted gas chromatography mass spectrometry (GC-MS) approaches. Combination of univariate and multivariate statistical treatment identified significant alterations of 42 and 32 metabolites in tissue and serum samples of IDC, respectively when compared to control. Some of the metabolite changes from tissue were also reflected in serum, indicating a bi-directional interaction of metabolites in IDC. Additionally, 8 tissue metabolites and 9 serum metabolites showed progressive change from control to benign to IDC suggesting their possible role in malignant transformation. We have identified a panel of three metabolites viz. tryptophan, tyrosine, and creatine in tissue and serum, which could be useful in screening of IDC subjects from both control and benign. The metabolomic alterations in IDC showed perturbations in purine and pyrimidine metabolism, amino sugar metabolism, amino acid metabolism, fatty acid biosynthesis etc. Comprehensively, this study provides valuable insights into metabolic adaptations of IDC, which can help to identify diagnostic markers as well as potential therapeutic targets. PMID: 29416801 [PubMed]

Patients with Treatment-Requiring Chronic Graft versus Host Disease after Allogeneic Stem Cell Transplantation Have Altered Metabolic Profiles due to the Disease and Immunosuppressive Therapy: Potential Implication for Biomarkers.

Fri, 09/02/2018 - 13:50
Patients with Treatment-Requiring Chronic Graft versus Host Disease after Allogeneic Stem Cell Transplantation Have Altered Metabolic Profiles due to the Disease and Immunosuppressive Therapy: Potential Implication for Biomarkers. Front Immunol. 2017;8:1979 Authors: Reikvam H, Grønningsæter IS, Mosevoll KA, Lindås R, Hatfield K, Bruserud Ø Abstract Chronic graft versus host disease (cGVHD) is a common long-term complication after allogeneic hematopoietic stem cell transplantation. The objective of our study was to compare the metabolic profiles for allotransplant recipients and thereby identify metabolic characteristics of patients with treatment-requiring cGVHD. The study included 51 consecutive patients (29 men and 22 women; median age: 44 years, range: 15-66 years) transplanted with peripheral blood stem cells derived from human leukocyte antigen-matched family donors. All serum samples investigated by global metabolomic profiling were collected approximately 1 year posttransplant (median 358 days). Thirty-one of the 51 patients (61%) had cGVHD 1 year posttransplant. The affected organs were (number of patients) liver/bile duct (23), eyes (15), gastrointestinal tract (14), skin (13), mouth (10), lungs (3), and urogenital tract (1). We compared the metabolic profile for patients with and without cGVHD, and a Random Forrest Classification Analysis then resulted in 75% accuracy in differentiating the two groups. The 30 top-ranked metabolites from this comparison included increased levels of bile acids, several metabolites from the cytokine-responsive kynurenine pathway for tryptophan degradation, pro-inflammatory lipid metabolites, phenylalanine and tyrosine metabolites derived from the gut microbial flora, and metabolites reflecting increased oxidative stress. However, nine of these 30 top-ranked metabolites were probably altered due to cyclosporine or steroid treatment, and we therefore did a hierarchical clustering analysis including all 51 patients but only based on the other 21 cGVHD-specific metabolites. This analysis identified three patient subsets: one cluster included mainly patients without cGVHD and had generally low metabolite levels; another cluster included mainly patients with cGVHD (most patients with at least three affected organs) and high metabolite levels, and the last intermediate group including cGVHD patients with limited organ involvement. We conclude that allotransplant recipients with cGVHD have an altered metabolic profile caused both by the disease and its immunosuppressive treatment. PMID: 29416533 [PubMed]

Urinary metabolic profiling of asymptomatic acute intermittent porphyria using a rule-mining-based algorithm.

Fri, 09/02/2018 - 13:50
Urinary metabolic profiling of asymptomatic acute intermittent porphyria using a rule-mining-based algorithm. Metabolomics. 2018;14(1):10 Authors: Luck M, Schmitt C, Talbi N, Gouya L, Caradeuc C, Puy H, Bertho G, Pallet N Abstract Introduction: Metabolomic profiling combines Nuclear Magnetic Resonance spectroscopy with supervised statistical analysis that might allow to better understanding the mechanisms of a disease. Objectives: In this study, the urinary metabolic profiling of individuals with porphyrias was performed to predict different types of disease, and to propose new pathophysiological hypotheses. Methods: Urine 1H-NMR spectra of 73 patients with asymptomatic acute intermittent porphyria (aAIP) and familial or sporadic porphyria cutanea tarda (f/sPCT) were compared using a supervised rule-mining algorithm. NMR spectrum buckets bins, corresponding to rules, were extracted and a logistic regression was trained. Results: Our rule-mining algorithm generated results were consistent with those obtained using partial least square discriminant analysis (PLS-DA) and the predictive performance of the model was significant. Buckets that were identified by the algorithm corresponded to metabolites involved in glycolysis and energy-conversion pathways, notably acetate, citrate, and pyruvate, which were found in higher concentrations in the urines of aAIP compared with PCT patients. Metabolic profiling did not discriminate sPCT from fPCT patients. Conclusion: These results suggest that metabolic reprogramming occurs in aAIP individuals, even in the absence of overt symptoms, and supports the relationship that occur between heme synthesis and mitochondrial energetic metabolism. PMID: 29416446 [PubMed]

Evaluation of autophagy inducers in epithelial cells carrying the ΔF508 mutation of the cystic fibrosis transmembrane conductance regulator CFTR.

Fri, 09/02/2018 - 13:50
Evaluation of autophagy inducers in epithelial cells carrying the ΔF508 mutation of the cystic fibrosis transmembrane conductance regulator CFTR. Cell Death Dis. 2018 Feb 07;9(2):191 Authors: Zhang S, Stoll G, Pedro JMBS, Sica V, Sauvat A, Obrist F, Kepp O, Li Y, Maiuri L, Zamzami N, Kroemer G Abstract Cystic Fibrosis (CF) due to the ΔF508 mutation of cystic fibrosis transmembrane conductance regulator (CFTR) can be treated with a combination of cysteamine and Epigallocatechin gallate (EGCG). Since ECGC is not a clinically approved drug, we attempted to identify other compounds that might favourably interact with cysteamine to induce autophagy and thus rescuing the function of ΔF508 CFTR as a chloride channel in the plasma membrane. For this, we screened a compound library composed by chemically diverse autophagy inducers for their ability to enhance autophagic flux in the presence of cysteamine. We identified the antiarrhythmic Ca2+ channel blocker amiodarone, as an FDA-approved drug having the property to cooperate with cysteamine to stimulate autophagy in an additive manner. Amiodarone promoted the re-expression of ΔF508 CFTR protein in the plasma membrane of respiratory epithelial cells. Hence, amiodarone might be yet another compound for the etiological therapy of CF in patients bearing the ΔF508 CFTR mutation. PMID: 29415993 [PubMed - in process]

Chromatographic Methods to Evaluate Nutritional Quality in Oat.

Fri, 09/02/2018 - 13:50
Related Articles Chromatographic Methods to Evaluate Nutritional Quality in Oat. Methods Mol Biol. 2017;1536:115-125 Authors: Montilla-Bascón G, Broeckling CD, Hoekenga OA, Prats E, Sorrells M, Isidro-Sánchez J Abstract Oats (A. sativa L.) have an important and positive role in human diet and health. The health benefits of oats are attributed to its multifunctional characteristic and nutritional profile, being an important source of soluble dietary fiber, well-balanced proteins, unsaturated fatty acids, vitamins, essential minerals, and a good source of natural antioxidants. These antioxidants include the avenanthramides (Avns) and avenalumic acids, which are unique to oats among cereals. High-performance liquid chromatography allows a simultaneous quantification of free amino acids and biogenic amines in oat samples as their OPA/FMOC-CL (o-phthalaldehyde/9-fluorenylmethoxycarbonyl chloride) derivatives. In addition, an ultra-performance liquid chromatography/mass spectrometry method was developed to quantify and characterize avenanthramides contained in oat samples. PMID: 28132146 [PubMed - indexed for MEDLINE]

Serum Metabolomic Profiles Identify ER-Positive Early Breast Cancer Patients at Increased Risk of Disease Recurrence in a Multicenter Population.

Fri, 09/02/2018 - 13:50
Related Articles Serum Metabolomic Profiles Identify ER-Positive Early Breast Cancer Patients at Increased Risk of Disease Recurrence in a Multicenter Population. Clin Cancer Res. 2017 Mar 15;23(6):1422-1431 Authors: Hart CD, Vignoli A, Tenori L, Uy GL, Van To T, Adebamowo C, Hossain SM, Biganzoli L, Risi E, Love RR, Luchinat C, Di Leo A Abstract Purpose: Detecting signals of micrometastatic disease in patients with early breast cancer (EBC) could improve risk stratification and allow better tailoring of adjuvant therapies. We previously showed that postoperative serum metabolomic profiles were predictive of relapse in a single-center cohort of estrogen receptor (ER)-negative EBC patients. Here, we investigated this further using preoperative serum samples from ER-positive, premenopausal women with EBC who were enrolled in an international phase III trial.Experimental Design: Proton nuclear magnetic resonance (NMR) spectroscopy of 590 EBC samples (319 with relapse or ≥6 years clinical follow-up) and 109 metastatic breast cancer (MBC) samples was performed. A Random Forest (RF) classification model was built using a training set of 85 EBC and all MBC samples. The model was then applied to a test set of 234 EBC samples, and a risk of recurrence score was generated on the basis of the likelihood of the sample being misclassified as metastatic.Results: In the training set, the RF model separated EBC from MBC with a discrimination accuracy of 84.9%. In the test set, the RF recurrence risk score correlated with relapse, with an AUC of 0.747 in ROC analysis. Accuracy was maximized at 71.3% (sensitivity, 70.8%; specificity, 71.4%). The model performed independently of age, tumor size, grade, HER2 status and nodal status, and also of Adjuvant! Online risk of relapse score.Conclusions: In a multicenter group of EBC patients, we developed a model based on preoperative serum metabolomic profiles that was prognostic for disease recurrence, independent of traditional clinicopathologic risk factors. Clin Cancer Res; 23(6); 1422-31. ©2017 AACR. PMID: 28082280 [PubMed - indexed for MEDLINE]

Mining Microbial Signals for Enhanced Biodiscovery of Secondary Metabolites.

Fri, 09/02/2018 - 13:50
Related Articles Mining Microbial Signals for Enhanced Biodiscovery of Secondary Metabolites. Methods Mol Biol. 2017;1539:287-300 Authors: Reen FJ, Gutiérrez-Barranquero JA, O'Gara F Abstract The advent of metagenomics based biodiscovery has provided researchers with previously unforeseen access to the rich tapestry of natural bioactivity that exists in the biosphere. Unhindered by the "culturable bottleneck" that has severely limited the translation of the genetic potential that undoubtedly exists in nature, metagenomics nonetheless requires ongoing technological developments to maximize its efficacy and applicability to the discovery of new chemical entities.Here we describe methodologies for the detection and isolation of quorum sensing (QS) signal molecules from metagenomics libraries. QS signals have already shown considerable potential for the activation and "awakening" of biosynthetic gene clusters, bridging the existing divide between the natural product repertoire and the natural biosynthetic biodiversity hinted at by nature's blueprint. The QS pipeline from high-throughput robotics to functional screening and hit isolation is detailed, highlighting the multidisciplinary nature of progressive biodiscovery programs. PMID: 27900698 [PubMed - indexed for MEDLINE]

Retrospective analysis of pesticide metabolites in urine using liquid chromatography coupled to high-resolution mass spectrometry.

Fri, 09/02/2018 - 13:50
Related Articles Retrospective analysis of pesticide metabolites in urine using liquid chromatography coupled to high-resolution mass spectrometry. Talanta. 2016 Nov 01;160:547-555 Authors: López A, Dualde P, Yusà V, Coscollà C Abstract A comprehensive retrospective analysis of pesticide metabolites in urine was developed, using liquid chromatography coupled to Orbitrap high-resolution mass spectrometry (UHPLC-HRMS) that includes both post-run target (suspect screening) and non-target screening. An accurate-mass database comprising 263 pesticide metabolites was built and used for the post-run screening analysis. For non-target analysis, a "fragmentation-degradation" relationship strategy was selected. The proposed methodology was applied to 49 real urine samples from pregnant women. In the post-target analysis 26 pesticide metabolites were tentatively identified, 8 of which (2-diethylamino-6-methyl-pyrimidinol; 3-ketocarbofuran; 4,6-dimethoxy-2-pyrimidinamine; 4-hydroxy-2-isporopyl-6-methylpyrimidine; diethyl malate; diethyl maleate; N-(2-Ethyl-6-methylphenyl)-2-hydroxyacetamide and propachlor oxanilic acid ) were confirmed using analytical standards. Likewise, one unknown degradation product, methyl-N-phenylcarbamate was elucidated in the non-target screening. Finally, the real urine samples were grouped according to their origin applying a metabolomic approach. PMID: 27591649 [PubMed - indexed for MEDLINE]

metabolomics; +31 new citations

Thu, 08/02/2018 - 16:05
31 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 2018/02/08PubMed comprises more than millions of 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.

metabolomics; +31 new citations

Thu, 08/02/2018 - 13:02
31 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 2018/02/08PubMed comprises more than millions of 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.

metabolomics; +21 new citations

Wed, 07/02/2018 - 15:56
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 2018/02/07PubMed comprises more than millions of 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.

metabolomics; +21 new citations

Wed, 07/02/2018 - 12:55
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 2018/02/07PubMed comprises more than millions of 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.

metabolomics; +20 new citations

Tue, 06/02/2018 - 15:43
20 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 2018/02/06PubMed comprises more than millions of 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.

metabolomics; +20 new citations

Tue, 06/02/2018 - 12:42
20 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 2018/02/06PubMed comprises more than millions of 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.

Jasmonate-Responsive MYB Factors Spatially Repress Rutin Biosynthesis in Fagopyrum Tataricum.

Sat, 03/02/2018 - 14:28
Jasmonate-Responsive MYB Factors Spatially Repress Rutin Biosynthesis in Fagopyrum Tataricum. J Exp Bot. 2018 Jan 31;: Authors: Zhang K, Logacheva MD, Meng Y, Hu J, Wan D, Li L, Dagmar J, Wang Z, Georgiev MI, Yu Z, Yang F, Yan M, Zhou M Abstract Jasmonates (JAs) are plant hormones that induce many secondary metabolites accumulation, such as rutin in buckwheat, via regulation of JAs-responsive transcription factors (TFs). Here, we report on the identification of a clade of JAs-responsive subgroup 4 MYB TFs, FtMYB13, FtMYB14, FtMYB15 and FtMYB16, directly repressing rutin biosynthesis in Fagopyrum tataricum. Immunoblot analysis showed that FtMYB13, FtMYB14 and FtMYB15 could be degraded via 26S proteasome in COI1-dependent JA signaling pathway, and this degradation is due to the SID motif in their C-terminus. Yeast two hybrid (Y2H) and Bimolecular Fluorescence Complementation (BiFC) assays revealed that FtMYB13, FtMYB14 and FtMYB15 interact with the importin protein 'Sensitive to ABA and Drought 2' (FtSAD2) in stem and inflorescence. Furthermore, the key repressor of JAs signaling FtJAZ1 specifically interacts with FtMYB13. Point mutation analysis showed that the conserved Asp residue of SID domain contributes to mediate the protein-protein interaction. Protoplasts transient activation assays demonstrated that FtMYB13, FtMYB14 and FtMYB15 directly repress phenylalanine ammonia lyase (FtPAL) gene expression and FtSAD2 and FtJAZ1 significantly promote the repressing activity of FtMYBs. These findings may ultimately be promising for further engineering of plant secondary metabolisms. PMID: 29394372 [PubMed - as supplied by publisher]

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