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; +56 new citations

Thu, 06/02/2020 - 16:11
56 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 2020/02/06PubMed 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; +56 new citations

Thu, 06/02/2020 - 13:11
56 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 2020/02/06PubMed 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; +37 new citations

Wed, 05/02/2020 - 22:08
37 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 2020/02/05PubMed 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.

Metabolomic profiling to evaluate the efficacy of proxalutamide, a novel androgen receptor antagonist, in prostate cancer cells.

Mon, 03/02/2020 - 12:43
Metabolomic profiling to evaluate the efficacy of proxalutamide, a novel androgen receptor antagonist, in prostate cancer cells. Invest New Drugs. 2020 Feb 01;: Authors: Qu F, Gu Y, Wang Q, He M, Zhou F, Sun J, Wang G, Peng Y Abstract Proxalutamide is a newly developed androgen receptor (AR) antagonist for the treatment of castration-resistant prostate cancer (PCa) that has entered phase III clinical trials. In the present study, we intended to elucidate the antitumor efficacy of proxalutamide through the metabolomic profiling of PCa cells. Two AR-positive PCa cell lines and two AR-negative PCa cell lines were investigated. Cell viability assays based on ATP quantitation were conducted. LC-Q/TOF-MS was used to analyze intracellular metabolites before or after the administration of proxalutamide and two other clinical AR antagonists (bicalutamide and enzalutamide). The results of this study showed that the inhibitory effect of proxalutamide on PCa cell proliferation was better than that of bicalutamide and enzalutamide, and proxalutamide preferentially affected AR-positive PCa cells over AR-negative cells. The metabolic composition of PCa cells changed significantly after proxalutamide administration, and these changes in response to proxalutamide were significantly different from those in the presence of the two other AR antagonists. In AR-positive cells, proxalutamide significantly decreased the intracellular levels of glutamine, glutamate, glutathione, cysteine, glycine, aspartate, uridine, cytidine and thymidine. However, the effects of the two other antagonists on these discriminant metabolites were ambiguous, and no changes in these metabolites were found in AR-negative cells. Our findings indicate that proxalutamide has inhibitory effects on glutamine metabolism, redox homeostasis and de novo pyrimidine synthesis in AR-positive PCa cells that enhance the cellular sensitivity to proxalutamide. PMID: 32008178 [PubMed - as supplied by publisher]

Metabolic Profiles Help Discriminate Mild Cognitive Impairment from Dementia Stage in Alzheimer's Disease.

Mon, 03/02/2020 - 12:43
Metabolic Profiles Help Discriminate Mild Cognitive Impairment from Dementia Stage in Alzheimer's Disease. J Alzheimers Dis. 2020 Jan 28;: Authors: Jääskeläinen O, Hall A, Tiainen M, van Gils M, Lötjönen J, Kangas AJ, Helisalmi S, Pikkarainen M, Hallikainen M, Koivisto A, Hartikainen P, Hiltunen M, Ala-Korpela M, Soininen P, Soininen H, Herukka SK Abstract Accurate differentiation between neurodegenerative diseases is developing quickly and has reached an effective level in disease recognition. However, there has been less focus on effectively distinguishing the prodromal state from later dementia stages due to a lack of suitable biomarkers. We utilized the Disease State Index (DSI) machine learning classifier to see how well quantified metabolomics data compares to clinically used cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD). The metabolic profiles were quantified for 498 serum and CSF samples using proton nuclear magnetic resonance spectroscopy. The patient cohorts in this study were dementia (with a clinical AD diagnosis) (N = 359), mild cognitive impairment (MCI) (N = 96), and control patients with subjective memory complaints (N = 43). DSI classification was conducted for MCI (N = 51) and dementia (N = 214) patients with low CSF amyloid-β levels indicating AD pathology and controls without such amyloid pathology (N = 36). We saw that the conventional CSF markers of AD were better at classifying controls from both dementia and MCI patients. However, quantified metabolic subclasses were more effective in classifying MCI from dementia. Our results show the consistent effectiveness of traditional CSF biomarkers in AD diagnostics. However, these markers are relatively ineffective in differentiating between MCI and the dementia stage, where the quantified metabolomics data provided significant benefit. PMID: 32007958 [PubMed - as supplied by publisher]

Metabolomic study of raw and bran-fried Atractylodis Rhizoma on rats with spleen deficiency.

Mon, 03/02/2020 - 12:43
Metabolomic study of raw and bran-fried Atractylodis Rhizoma on rats with spleen deficiency. J Pharm Biomed Anal. 2019 Dec 30;182:112927 Authors: Zhang BX, Qi XJ, Cai Q Abstract Atractylodis Rhizoma, a classical Chinese medicine, exhibits unambiguous therapeutic effect on spleen deficiency in China for decades. The aim of the present study was to explore the different effects on the composition and level of endogenous metabolites in rats with spleen deficiency after oral administration of raw and bran-fired Atractylodis Rhizoma, and to explain the mechanism of pharmacodynamic enhancement of the bran-fried Atractylodis Rhizoma from the perspective of metabolomics. With this purpose, spleen deficiency model was established by diet, excessive fatigue and bitter cold diarrhea. Then, Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of vasoactive intestinal peptide (VIP), Somatostatin (SS), substance P (SP) and succinodehydrogenase (SDH) in rats of each group, and to compare the contents of VIP, SS, SP and SDH among groups. UHPLC-Q-TOF-MS based metabolomics was adopted to analyze the plasma from spleen deficiency rats and control rats. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify differences of metabolic profiles in rats among the control group and the model group;The OPLS-DA were used to analyze the effects of raw and bran-fried Atractylodis Rhizoma on the same metabolites. The results showed that compared with the control group, the contents of VIP, SS, SP and SDH in the plasma of model group decreased, which proved the success of the model group. Compared with model group, the contents of VIP, SS, SP and SDH in the plasma of raw and bran-fried Atractylodis Rhizoma increased, and the effect of bran-fried Atractylodis Rhizoma was better than that of raw Atractylodis Rhizoma. Metabolomics results showed that seventeen different metabolites of spleen deficiency were screened out in the plasma of rats with spleen deficiency compared with the control group. Among them, Nicotinic acid, Dihydrofolic acid, Pantetheine 4'-phosphate and Photophatidylcholine (PC) were the metabolites significantly associated with spleen deficiency, and bran-fried Atractylodis Rhizoma had better intervention and regulation. Through the analysis of metabolic pathways related to these different metabolites of spleen deficiency, and primarily involved in glucosamine metabolism, one carbon pool by folate and so on. This study showed that Atractylodis Rhizoma could provide satisfactory therapeutic effects on spleen deficiency and metabolomics study can be utilized to further understand the molecular mechanisms. PMID: 32007825 [PubMed - as supplied by publisher]

The impact of phenanthrene on membrane phospholipids and its biodegradation by Sphingopyxis soli.

Mon, 03/02/2020 - 12:43
The impact of phenanthrene on membrane phospholipids and its biodegradation by Sphingopyxis soli. Ecotoxicol Environ Saf. 2020 Jan 30;192:110254 Authors: Shon JC, Noh YJ, Kwon YS, Kim JH, Wu Z, Seo JS Abstract The direct interactions of bacterial membranes and polycyclic aromatic hydrocarbons (PAHs) strongly influence the biological processes, such as metabolic activity and uptake of substrates due to changes in membrane lipids. However, the elucidation of adaptation mechanisms as well as membrane phospholipid alterations in the presence of phenanthrene (PHE) from α-proteobacteria has not been fully explored. This study was conducted to define the degradation efficiency of PHE by Sphingopyxis soli strain KIT-001 in a newly isolated from Jeonju river sediments and to characterize lipid profiles in the presence of PHE in comparison to cells grown on glucose using quantitative lipidomic analysis. This strain was able to respectively utilize 1-hydroxy-2-naphthoic acid and salicylic acid as sole carbon source and approximately 90% of PHE (50 mg/L) was rapidly degraded via naphthalene route within 1 day incubation. In the cells grown on PHE, strain KIT-001 appeared to dynamically change profiles of metabolite and lipid in comparison to cells grown on glucose. The levels of primary metabolites, phosphatidylethanolamines (PE), and phosphatidic acids (PA) were significantly decreased, whereas the levels of phosphatidylcholines (PC) and phosphatidylglycerols (PG) were significantly increased. The adaptation mechanism of Sphingopyxis sp. regarded mainly the accumulation of bilayer forming lipids and anionic lipids to adapt more quickly under restricted nutrition and toxicity condition. Hence, these findings are conceivable that strain KIT-001 has a good adaptive ability and biodegradation for PHE through the alteration of phospholipids, and will be helpful for applications for effective bioremediation of PAHs-contaminated sites. PMID: 32007746 [PubMed - as supplied by publisher]

Dose-escalation trial of budesonide in surfactant for prevention of bronchopulmonary dysplasia in extremely low gestational age high-risk newborns (SASSIE).

Sun, 02/02/2020 - 12:27
Related Articles Dose-escalation trial of budesonide in surfactant for prevention of bronchopulmonary dysplasia in extremely low gestational age high-risk newborns (SASSIE). Pediatr Res. 2020 Feb 01;: Authors: McEvoy CT, Ballard PL, Ward RM, Rower JE, Wadhawan R, Hudak ML, Weitkamp JH, Harris J, Asselin J, Chapin C, Ballard RA Abstract BACKGROUND: Initial trials of lung-targeted budesonide (0.25 mg/kg) in surfactant to prevent bronchopulmonary dysplasia (BPD) in premature infants have shown benefit; however, the optimal safe dose is unknown. METHODS: Dose-escalation study of budesonide (0.025, 0.05, 0.10 mg/kg) in calfactatant in extremely low gestational age neonates (ELGANs) requiring intubation at 3-14 days. Tracheal aspirate (TA) cytokines, blood budesonide concentrations, and untargeted blood metabolomics were measured. Outcomes were compared with matched infants receiving surfactant in the Trial Of Late SURFactant (TOLSURF). RESULTS: Twenty-four infants with mean gestational age 25.0 weeks and 743 g birth weight requiring mechanical ventilation were enrolled at mean age 6 days. Budesonide was detected in the blood of all infants with a half-life of 3.4 h. Of 11 infants with elevated TA cytokine levels at baseline, treatment was associated with sustained decrease (mean 65%) at all three dosing levels. There were time- and dose-dependent decreases in blood cortisol concentrations and changes in total blood metabolites. Respiratory outcomes did not differ from the historic controls. CONCLUSIONS: Budesonide/surfactant had no clinical respiratory benefit at any dosing levels for intubated ELGANs. One-tenth the dose used in previous trials had minimal systemic metabolic effects and appeared effective for lung-targeted anti-inflammatory action. PMID: 32006953 [PubMed - as supplied by publisher]

Bacillus spore awakening: recent discoveries and technological developments.

Sun, 02/02/2020 - 12:27
Related Articles Bacillus spore awakening: recent discoveries and technological developments. Curr Opin Biotechnol. 2020 Jan 29;64:110-115 Authors: Xing Y, Harper WF Abstract Elucidating the mechanistic basis of spore germination and outgrowth remains a difficult challenge with crucial implications in the numerous scientific and engineering disciplines. Omics studies have revealed numerous new biochemical insights and single-spore studies link molecular insights directly with spore heterogeneity behaviors. This field is expected to advance at greater speed with the application of newer omics tools such as metabolomics and ingenious combination of omics with single-spore techniques. Combining the modern techniques with traditional techniques will resolve the inconsistencies in literature such as the case of protein synthesis in germination. Lastly, mining of the experimental data with data science tools is expected to reveal new insights in the regulatory networks in spore germination and outgrowth. PMID: 32006878 [PubMed - as supplied by publisher]

Metabolite profiling reveals a complex response of plants to application of plant growth-promoting endophytic bacteria.

Sun, 02/02/2020 - 12:27
Related Articles Metabolite profiling reveals a complex response of plants to application of plant growth-promoting endophytic bacteria. Microbiol Res. 2020 Jan 25;234:126421 Authors: Mahmood A, Kataoka R Abstract Endophytic bacteria have been explored for their role in plant growth promotion, however, not much has been explored in cucumber. The metabolomic response of plants to application of such microbes also remains largely unknown. Thus, we investigated the application of endophytic bacteria to cucumber to infer their role in plant growth promotion and document metabolome response. The lowest healthy leaf-stalks were sampled from four differently sourced cucumber plants, and endophytic bacteria were isolated after surface disinfection. Initial plant growth-promoting (PGP) screening was performed to identify PGP strains out of numerous isolates, and five strains (Strains 4=Curtobacterium spp., 72=Brevibacillus spp., 167=Paenibacillus spp., 193=Bacillus spp., and 227=Microbacterium spp.) were selected based on their contribution to root growth compared with the control. The selected strains were further evaluated in pot experiments, axenic PGP trait assays, and metabolomic analysis. Results revealed that the selected isolates possessed different qualitative characteristics among indole acetic acid, siderophore production, phosphate solubilization, and 1-aminocyclopropane-1-carboxylate (ACC)-deaminase and nifH genes, and all isolates significantly enhanced plant growth in both pot experiments compared with the uninoculated control and fertilizer control. Metabolomic profiling revealed that both strains affected the plant metabolomes compared with the uninoculated control. Around 50 % of the metabolites explored had higher concentrations in either or both bacteria-applied plants compared with the uninoculated control. Differences were observed in both strains' regulation of metabolites, although both enhanced root growth near equally. Overall, endophytic bacteria significantly enhanced plant growth and tended to produce or induce release of certain metabolites within the plant endosphere. PMID: 32006789 [PubMed - as supplied by publisher]

The compatibility effects of sini decoction against doxorubicin-induced heart failure in rats revealed by mass spectrometry-based serum metabolite profiling and computational analysis.

Sun, 02/02/2020 - 12:27
Related Articles The compatibility effects of sini decoction against doxorubicin-induced heart failure in rats revealed by mass spectrometry-based serum metabolite profiling and computational analysis. J Ethnopharmacol. 2020 Jan 29;:112618 Authors: Zhou Q, Meng P, Zhang Y, Chen P, Wang H, Tan G Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Sini decoction (SND) is a famous Traditional Chinese Medicine (TCM) formula composed of Acontium carmichaeli, Zingiber officinale and Glycyrrhiza uralensis, which is considered as an efficient formula against doxorubicin (DOX)-induced heart failure. But the compatibility mechanism of SND remains unclear. AIM OF THE STUDY: The present study aimed to investigate the compatibility mechanism of SND against DOX-induced heart failure in rats. MATERIALS AND METHODS: Mass spectrometry-based serum metabolomics were performed. The relative distance values (RDVs) of SND, A. carmichaeli-free decoction (ACFD), Z. officinale-free decoction (ZOFD) and G. uralensis-free decoction (GUFD) treated groups from the control/DOX groups in multidimensional space were calculated to provide a measure of compatibility effect of SND. SND, ACFD, ZOFD, GUFD-targeted metabolic pathways were identified and compared to investigate the synergistic mechanism of SND by computational systems analysis. Real-time quantitative PCR was further employed to validate the key metabolic pathways at the level of the gene. RESULTS: The RDVs combined with the hemodynamic and biochemical analysis showed that the protection effects were sorted as SND > GUFD > ZOFD > ACFD. It revealed that DOX-induced heart failure perturbed 16 metabolic pathways, and SND, GUFD, ZOFD and ACFD-treated groups could significantly reversed 12, 10, 7 and 6 metabolic pathways of these 16 metabolic pathways, respectively. Metabolic pathway and RT-PCR analysis indicated that both SND and GUFD could protect DOX-induced heart failure mainly by regulating PLA2-COX pathway and PLA2-CYP pathway. CONCLUSION: It can be concluded that A. carmichaeli played an essential role in attenuation of DOX-induced heart failure among the three herb constituents of SND and the constituent herbs mutually reinforced each other. This work demonstrated that metabolomics combined with computational systems analysis was a promising tool for uncovering the compatibility effects of TCM. PMID: 32006632 [PubMed - as supplied by publisher]

BioMagResBank (BMRB) as a Resource for Structural Biology.

Sun, 02/02/2020 - 12:27
Related Articles BioMagResBank (BMRB) as a Resource for Structural Biology. Methods Mol Biol. 2020;2112:187-218 Authors: Romero PR, Kobayashi N, Wedell JR, Baskaran K, Iwata T, Yokochi M, Maziuk D, Yao H, Fujiwara T, Kurusu G, Ulrich EL, Hoch JC, Markley JL Abstract The Biological Magnetic Resonance Data Bank (BioMagResBank or BMRB), founded in 1988, serves as the archive for data generated by nuclear magnetic resonance (NMR) spectroscopy of biological systems. NMR spectroscopy is unique among biophysical approaches in its ability to provide a broad range of atomic and higher-level information relevant to the structural, dynamic, and chemical properties of biological macromolecules, as well as report on metabolite and natural product concentrations in complex mixtures and their chemical structures. BMRB became a core member of the Worldwide Protein Data Bank (wwPDB) in 2007, and the BMRB archive is now a core archive of the wwPDB. Currently, about 10% of the structures deposited into the PDB archive are based on NMR spectroscopy. BMRB stores experimental and derived data from biomolecular NMR studies. Newer BMRB biopolymer depositions are divided about evenly between those associated with structure determinations (atomic coordinates and supporting information archived in the PDB) and those reporting experimental information on molecular dynamics, conformational transitions, ligand binding, assigned chemical shifts, or other results from NMR spectroscopy. BMRB also provides resources for NMR studies of metabolites and other small molecules that are often macromolecular ligands and/or nonstandard residues. This chapter is directed to the structural biology community rather than the metabolomics and natural products community. Our goal is to describe various BMRB services offered to structural biology researchers and how they can be accessed and utilized. These services can be classified into four main groups: (1) data deposition, (2) data retrieval, (3) data analysis, and (4) services for NMR spectroscopists and software developers. The chapter also describes the NMR-STAR data format used by BMRB and the tools provided to facilitate its use. For programmers, BMRB offers an application programming interface (API) and libraries in the Python and R languages that enable users to develop their own BMRB-based tools for data analysis, visualization, and manipulation of NMR-STAR formatted files. BMRB also provides users with direct access tools through the NMRbox platform. PMID: 32006287 [PubMed - in process]

Screening of Biomarkers Related to Ovarian Maturation and Spawning in Blunt Snout Bream (Megalobrama amblycephala) Based on Metabolomics and Transcriptomics.

Sun, 02/02/2020 - 12:27
Related Articles Screening of Biomarkers Related to Ovarian Maturation and Spawning in Blunt Snout Bream (Megalobrama amblycephala) Based on Metabolomics and Transcriptomics. Mar Biotechnol (NY). 2020 Jan 31;: Authors: Yi S, Liu LF, Zhou LF, Zhao BW, Wang WM, Gao ZX Abstract In fish breeding practices, gamete maturity of females is vital to reproductive success. For some species, it is possible to estimate the female maturation status based on abdomen observation, but quite difficult for some species which mature at big size. To screen out the potential biomarker in fish blood relating to female maturation, we employed the approach integrating the UPLC-MS/MS and RNA-seq techniques to investigate the metabolites and genes reflecting the sexual maturation and spawning of female blunt snout bream Megalobrama amblycephala. The study included four groups, 1-year-old immature female individuals, 2-year-old immature female individuals, 2-year-old sexually mature female individuals, and 2-year-old sexually mature female individuals after 24 h of successful spawning. The upregulated metabolites in mature females were involved in "steroid hormone biosynthesis," "metabolic pathways," "glycerophospholipid metabolism," etc. compared with those of immature individuals. As the key intermediate of steroid hormone biosynthesis, 17α-hydroxypregnenolone exhibited the highest level in 2-year-old mature females than in the immature females. Meanwhile, the metabolites (i.e., dodecanoic acid and myristic acid) participating in fatty acid synthesis exhibited much lower levels in the females after spawning than those before spawning. In addition to the metabolites, the genes involved in ovarian steroidogenesis were significantly upregulated in the 2-year-old immature females compared to the 1-year-old immature females, indicating that the ovarian steroidogenesis plays important roles in ovarian development of M. amblycephala at the early stages. The significant upregulation of genes (i.e., itpr1, camk2, and mekk2) involved in the "GnRH signaling pathway" was observed in the mature females compared with the immature females, which indicated that the estrogen levels increased after female maturation in M. amblycephala. Moreover, many genes (e.g., gck, creb1, tf2-9, ryr2, asgr1, and creb1) regulating insulin secretion and thyroid hormone synthesis were significantly downregulated after female spawning. The dynamics of gene expression and metabolites observed in this study provide novel cues for guiding fish practical artificial reproduction. PMID: 32006128 [PubMed - as supplied by publisher]

Effects of high-intensity interval training on adipose tissue lipolysis, inflammation, and metabolomics in aged rats.

Sun, 02/02/2020 - 12:27
Related Articles Effects of high-intensity interval training on adipose tissue lipolysis, inflammation, and metabolomics in aged rats. Pflugers Arch. 2020 Jan 31;: Authors: Sun L, Li FH, Li T, Min Z, Yang LD, Gao HE, Wu DS, Xie T Abstract High-intensity interval training (HIIT) is a time-efficient alternative to moderate-intensity continuous training (MICT) to improve metabolic health in older individuals. However, differences in adipose tissue metabolism between these two approaches are unclear. Here, we evaluated the effects of HIIT and MICT on metabolic phenotypes in aged rats. HIIT significantly decreased fat mass, increased percent lean mass, decreased fat-to-lean ratio, reduced serum high-sensitivity C-reactive protein, increased serum interleukin-10 levels, and decreased perirenal adipose tissue leptin compared with rats in the sedentary (SED) group. HIIT also increased pregnenolone, cortisol, and corticosterone in both adipose tissue and serum. Both exercise modalities enhanced hormone-sensitive lipase and adipose triglyceride lipase expression compared with the SED group and decreased palmitic acid, stearic acid, octadecadienoic acid, urea, 1-heptadecanol, and α-tocopherol. MICT was related to glycerolipid metabolism, whereas HIIT was related to steroid hormone biosynthesis. Overall, HIIT showed more favorable regulation of anti-inflammatory activity than MICT. PMID: 32006095 [PubMed - as supplied by publisher]

Endogenous FGF21-signaling controls paradoxical obesity resistance of UCP1-deficient mice.

Sun, 02/02/2020 - 12:27
Related Articles Endogenous FGF21-signaling controls paradoxical obesity resistance of UCP1-deficient mice. Nat Commun. 2020 Jan 31;11(1):624 Authors: Keipert S, Lutter D, Schroeder BO, Brandt D, Ståhlman M, Schwarzmayr T, Graf E, Fuchs H, de Angelis MH, Tschöp MH, Rozman J, Jastroch M Abstract Uncoupling protein 1 (UCP1) executes thermogenesis in brown adipose tissue, which is a major focus of human obesity research. Although the UCP1-knockout (UCP1 KO) mouse represents the most frequently applied animal model to judge the anti-obesity effects of UCP1, the assessment is confounded by unknown anti-obesity factors causing paradoxical obesity resistance below thermoneutral temperatures. Here we identify the enigmatic factor as endogenous FGF21, which is primarily mediating obesity resistance. The generation of UCP1/FGF21 double-knockout mice (dKO) fully reverses obesity resistance. Within mild differences in energy metabolism, urine metabolomics uncover increased secretion of acyl-carnitines in UCP1 KOs, suggesting metabolic reprogramming. Strikingly, transcriptomics of metabolically important organs reveal enhanced lipid and oxidative metabolism in specifically white adipose tissue that is fully reversed in dKO mice. Collectively, this study characterizes the effects of endogenous FGF21 that acts as master regulator to protect from diet-induced obesity in the absence of UCP1. PMID: 32005798 [PubMed - in process]

Transcriptome analysis and functional characterization of oxidosqualene cyclases of the arjuna triterpene saponin pathway.

Sun, 02/02/2020 - 12:27
Related Articles Transcriptome analysis and functional characterization of oxidosqualene cyclases of the arjuna triterpene saponin pathway. Plant Sci. 2020 Mar;292:110382 Authors: Srivastava G, Sandeep, Garg A, Misra RC, Chanotiya CS, Ghosh S Abstract Arjuna (Terminalia arjuna) tree has been popular in Indian traditional medicine to treat cardiovascular ailments. The tree accumulates bioactive triterpene glycosides (saponins) and aglycones (sapogenins), in a tissue-preferential manner. Oleanane triterpenes/saponins (derived from β-amyrin) with potential cardioprotective function predominantly accumulate in the bark. However, arjuna triterpene saponin pathway enzymes remain to be identified and biochemically characterized. Here, we employed a combined transcriptomics, metabolomics and biochemical approach to functionally define a suite of oxidosqualene cyclases (OSCs) that catalyzed key reactions towards triterpene scaffold diversification. De novo assembly of 131 millions Illumina NextSeq500 sequencing reads obtained from leaf and stem bark samples led to a total of 156,650 reference transcripts. Four distinct OSCs (TaOSC1-4) with 54-71 % sequence identities were identified and functionally characterized. TaOSC1, TaOSC3 and TaOSC4 were biochemically characterized as β-amyrin synthase, cycloartenol synthase and lupeol synthase, respectively. However, TaOSC2 was found to be a multifunctional OSC producing both α-amyrin and β-amyrin, but showed a preference for α-amyrin product. Both TaOSC1 and TaOSC2 produced β-amyrin, the direct precursor for oleanane triterpene/saponin biosynthesis; but, TaOSC1 transcript expressed preferentially in bark, suggesting a major role of TaOSC1 in the biosynthesis of oleanane triterpenes/saponins in bark. PMID: 32005387 [PubMed - in process]

Amphotericin B biosynthesis in Streptomyces nodosus: quantitative analysis of metabolism via LC-MS/MS based metabolomics for rational design.

Sun, 02/02/2020 - 12:27
Related Articles Amphotericin B biosynthesis in Streptomyces nodosus: quantitative analysis of metabolism via LC-MS/MS based metabolomics for rational design. Microb Cell Fact. 2020 Jan 31;19(1):18 Authors: Zhang B, Zhou YT, Jiang SX, Zhang YH, Huang K, Liu ZQ, Zheng YG Abstract BACKGROUND: Amphotericin B (AmB) is widely used against fungal infection and produced mainly by Streptomyces nodosus. Various intracellular metabolites of S. nodosus were identified during AmB fermentation, and the key compounds that related to the cell growth and biosynthesis of AmB were analyzed by principal component analysis (PCA) and partial least squares (PLS). RESULTS: Rational design that based on the results of metabolomics was employed to improve the AmB productivity of Streptomyces nodosus, including the overexpression of genes involved in oxygen-taking, precursor-acquiring and product-exporting. The AmB yield of modified strain S. nodosus VMR4A was 6.58 g/L, which was increased significantly in comparison with that of strain S. nodosus ZJB2016050 (5.16 g/L). This was the highest yield of AmB reported so far, and meanwhile, the amount of by-product amphotericin A (AmA) was decreased by 45%. Moreover, the fermentation time of strain S. nodosus VMR4A was shortened by 24 h compared with that of strain. The results indicated that strain S. nodosus VMR4A was an excellent candidate for the industrial production of AmB because of its high production yield, low by-product content and the fast cell growth. CONCLUSIONS: This study would lay the foundation for improving the AmB productivity through metabolomics analysis and overexpression of key enzymes. PMID: 32005241 [PubMed - in process]

metabolomics; +24 new citations

Sat, 01/02/2020 - 15:07
24 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 2020/02/01PubMed 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; +24 new citations

Sat, 01/02/2020 - 12:06
24 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 2020/02/01PubMed 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; +29 new citations

Fri, 31/01/2020 - 14:51
29 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 2020/01/31PubMed 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.

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