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

Characterization of white tea metabolome: Comparison against green and black tea by a nontargeted metabolomics approach.

Mon, 22/05/2017 - 12:34
Characterization of white tea metabolome: Comparison against green and black tea by a nontargeted metabolomics approach. Food Res Int. 2017 Jun;96:40-45 Authors: Dai W, Xie D, Lu M, Li P, Lv H, Yang C, Peng Q, Zhu Y, Guo L, Zhang Y, Tan J, Lin Z Abstract White tea is considered the least processed form of tea and is reported to have a series of potent bioactivities, such as antioxidant, anti-inflammatory, anti-mutagenic, and anti-cancer activities. However, the chemical composition of white tea and the dynamic changes of the metabolites during the manufacturing process are far from clear. In this study, we applied a nontargeted metabolomics approach based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) to comprehensively profile the characteristic metabolites of white tea. There were significant differences in the content of amino acids, catechins, dimeric catechins, flavonol and flavone glycosides, and aroma precursors in white tea compared with green and black teas that were manufactured from the same fresh tea leaves. Furthermore, the dynamic changes of the metabolites in the tea samples with various withering durations of 0, 4, 8, 12, 16, 20, 24, 28, and 36 h were also profiled. This study offers a comprehensive characterization of the metabolites and their changes in white tea. PMID: 28528106 [PubMed - in process]

Mechanisms of the Amplifying Pathway of Insulin Secretion in the β Cell.

Mon, 22/05/2017 - 12:34
Mechanisms of the Amplifying Pathway of Insulin Secretion in the β Cell. Pharmacol Ther. 2017 May 17;: Authors: Kalwat MA, Cobb M Abstract Pancreatic islet β cells secrete insulin in response to nutrient secretagogues, like glucose, dependent on calcium influx and nutrient metabolism. One of the most intriguing qualities of β cells is their ability to use metabolism to amplify the amount of secreted insulin independent of further alterations in intracellular calcium. Many years studying this amplifying process have shaped our current understanding of β cell stimulus-secretion coupling; yet, the exact mechanisms of amplification have been elusive. Recent studies utilizing metabolomics, computational modeling, and animal models have progressed our understanding of the metabolic amplifying pathway of insulin secretion from the β cell. New approaches will be discussed which offer in-roads to a more complete model of β cell function. The development of β cell therapeutics may be aided by such a model, facilitating the targeting of aspects of the metabolic amplifying pathway which are unique to the β cell. PMID: 28527919 [PubMed - as supplied by publisher]

Maintenance of ATP Homeostasis Triggers Metabolic Shifts in Gas-Fermenting Acetogens.

Mon, 22/05/2017 - 12:34
Maintenance of ATP Homeostasis Triggers Metabolic Shifts in Gas-Fermenting Acetogens. Cell Syst. 2017 May 16;: Authors: Valgepea K, de Souza Pinto Lemgruber R, Meaghan K, Palfreyman RW, Abdalla T, Heijstra BD, Behrendorff JB, Tappel R, Köpke M, Simpson SD, Nielsen LK, Marcellin E Abstract Acetogens are promising cell factories for producing fuels and chemicals from waste feedstocks via gas fermentation, but quantitative characterization of carbon, energy, and redox metabolism is required to guide their rational metabolic engineering. Here, we explore acetogen gas fermentation using physiological, metabolomics, and transcriptomics data for Clostridium autoethanogenum steady-state chemostat cultures grown on syngas at various gas-liquid mass transfer rates. We observe that C. autoethanogenum shifts from acetate to ethanol production to maintain ATP homeostasis at higher biomass concentrations but reaches a limit at a molar acetate/ethanol ratio of ∼1. This regulatory mechanism eventually leads to depletion of the intracellular acetyl-CoA pool and collapse of metabolism. We accurately predict growth phenotypes using a genome-scale metabolic model. Modeling revealed that the methylene-THF reductase reaction was ferredoxin reducing. This work provides a reference dataset to advance the understanding and engineering of arguably the first carbon fixation pathway on Earth. PMID: 28527885 [PubMed - as supplied by publisher]

Structural characterization and discrimination of the Paris polyphylla var. yunnanensis and Paris vietnamensis based on metabolite profiling analysis.

Sun, 21/05/2017 - 12:03
Structural characterization and discrimination of the Paris polyphylla var. yunnanensis and Paris vietnamensis based on metabolite profiling analysis. J Pharm Biomed Anal. 2017 May 11;142:252-261 Authors: Kang LP, Huang YY, Zhan ZL, Liu DH, Peng HS, Nan TG, Zhang Y, Hao QX, Tang JF, Zhu SD, Yang G, Guo LP, Chen M, Huang LQ Abstract This study aimed to distinguish the rhizomes of Paris polyphylla var. yunnanensis (Franch) Hand Mazz (PPY) and Paris veitnamensis (Takht.) H. Li (PV) using metabolomics-based ultra high-performance liquid chromatography coupled with quadrupole time-of-fligh mass spectrometry (UHPLC/Q-TOF MS). First, the UHPLC/Q-TOF MS approach was optimized for metabolite profiling. Then, the MS data were processed using UNIFI™ combined with an in-house library to automatically characterize the metabolites. Based on the exact mass information, the fragmentation characteristics, and the retention time of compounds, and the fragmentation mechanism and retention behavior of steroidal glycosides in the references, the structures identified by UNIFI were further verified. Overall, 146 metabolites, including 42 potential new compounds, were identified or tentatively identified. Pattern recognition analysis of the PPY and PV MS data revealed that they were clearly separated, and 15 potential biomarkers for differentiating between them were selected. These biomarkers were subsequently used to successfully predict the genus of PPY and PV samples. These results indicated that metabolite profiling by UHPLC/Q-TOF MS is an effective, robust approach for determining the characteristic biomarkers that differentiate between TCM species with multiple botanical origins. PMID: 28527414 [PubMed - as supplied by publisher]

Essential hypertension: A filtered serum based metabolomics study.

Sun, 21/05/2017 - 12:03
Related Articles Essential hypertension: A filtered serum based metabolomics study. Sci Rep. 2017 May 19;7(1):2153 Authors: Ameta K, Gupta A, Kumar S, Sethi R, Kumar D, Mahdi AA Abstract Despite the easy and reliable methods of blood pressure measurement, the screening of essential hypertension (EH) is usually ignored due to delayed onset of symptoms. A probe into the biochemical changes in hypertension would serve as a welcome asset to provide insight into the mechanistic aspects of EH. Filtered serum samples from 64 EH patients and 59 healthy controls (HC) were analysed using 800 MHz nuclear magnetic resonance (NMR) spectroscopy. Application of principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) following receiver operating characteristic (ROC) curve of NMR data reveals significantly perturbed metabolites: alanine, arginine, methionine, pyruvate, adenine, and uracil. This set of metabolites correctly classified 99% of cases from HC and also showed excellent correlation in both isolated elevated diastolic blood pressure (DBP) cases and combined elevated systolic-diastolic blood pressure cases. Proton NMR metabolomics of EH may prove helpful in defining associated biomarkers and serve as an alternate diagnostic tool with judicious clinical assessment. PMID: 28526818 [PubMed - in process]

metabolomics; +16 new citations

Sat, 20/05/2017 - 14:18
16 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 2017/05/20PubMed 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.

Platelet lipidomics: a window of opportunity to assess cardiovascular risk?

Fri, 19/05/2017 - 14:06
Related Articles Platelet lipidomics: a window of opportunity to assess cardiovascular risk? Eur Heart J. 2017 May 17;: Authors: McFadyen JD, Meikle PJ, Peter K PMID: 28520938 [PubMed - as supplied by publisher]

Lower Levels of Cervicovaginal Tryptophan are Associated with Natural Clearance of Chlamydia in Women.

Fri, 19/05/2017 - 14:06
Related Articles Lower Levels of Cervicovaginal Tryptophan are Associated with Natural Clearance of Chlamydia in Women. J Infect Dis. 2017 May 17;: Authors: Jordan SJ, Olson KM, Barnes S, Wilson LS, Berryhill TF, Bakshi R, Brown LT, Press CG, Geisler WM Abstract Chlamydia trachomatis (Ct) infection causes significant morbidity. In vitro studies demonstrate Ct growth inhibition occurs by interferon-gamma (IFN-γ)-mediated depletion of intracellular tryptophan, and some Ct strains utilize extracellular indole to restore tryptophan levels. Whether tryptophan levels are associated with Ct infection in clearance humans remains unknown. We evaluated tryptophan, indole, and IFN-γ levels in cervicovaginal lavages from women with either naturally cleared Ct infection or persisting Ct infection. Women who cleared infection had significantly lower tryptophan levels and trended towards lower IFN-γ levels compared to women with persisting infection. Due to its volatility, indole was not measurable in either group. PMID: 28520912 [PubMed - as supplied by publisher]

From chromatogram to analyte to metabolite. How to pick horses for courses from the massive web-resources for mass spectral plant metabolomics.

Fri, 19/05/2017 - 14:06
Related Articles From chromatogram to analyte to metabolite. How to pick horses for courses from the massive web-resources for mass spectral plant metabolomics. Gigascience. 2017 May 17;: Authors: de Souza LP, Naake T, Tohge T, Fernie AR Abstract The grand challenge currently facing metabolomics is the expansion of the coverage of the metabolome from a minor percentage of the metabolic complement of the cell towards the level of coverage afforded by other post-genomic technologies such as transcriptomics and proteomics. In plants this problem is exacerbated by the sheer diversity of chemicals that constitute the metabolome with the number of metabolites in the plant kingdom generally being considered to be in excess of 200 000. In this review we focus on web-resources that can be exploited in order to improve analyte and ultimately metabolite identification and quantification. There is a wide range of available software that not only aids in this but also in the related area of peak alignment, however, for the uninitiated choosing which program to use is a daunting task. For this reason we provide an overview of the pros and cons of the software as well as comments regarding the level of programing skills required to effectively exploit their basic functions. In addition the torrent of available genome and transcriptome sequences that followed the advent of next-generation sequencing has opened up further valuable resources for metabolite identification. All things considered, we posit that only via a continued communal sharing of information such as that deposited in the databases described within the article are we likely to be able to make significant headway towards improving our coverage of the plant metabolome. PMID: 28520864 [PubMed - as supplied by publisher]

Challenges in metabolomics-based disease molecular classification: an analytical perspective.

Fri, 19/05/2017 - 14:06
Related Articles Challenges in metabolomics-based disease molecular classification: an analytical perspective. Bioanalysis. 2017 May 18;: Authors: Gao Y, Liu Q, Xu F PMID: 28520467 [PubMed - as supplied by publisher]

Integrated strategy for unknown EI-MS identification using quality control calibration curve, multivariate analysis, EI-MS spectral database, and retention index prediction.

Fri, 19/05/2017 - 14:06
Related Articles Integrated strategy for unknown EI-MS identification using quality control calibration curve, multivariate analysis, EI-MS spectral database, and retention index prediction. Anal Chem. 2017 May 18;: Authors: Matsuo T, Tsugawa H, Miyagawa H, Fukusaki E Abstract Compound identification using unknown electron ionization (EI) mass spectra in gas chromatography coupled with mass spectrometry (GC-MS) is challenging in untargeted metabolomics, natural product chemistry, or exposome research. While the total count of EI-MS records included in publicly or commercially available databases is over 900,000, efficient use of this huge database has not been achieved in metabolomics. Therefore, we proposed a 'four-step' strategy for the identification of biologically significant metabolites using an integrated cheminformatics approach: (i) Quality control calibration curve to reduce background noise, (ii) variable selection by hypothesis testing in principal component analysis for the efficient selection of target peaks, (iii) searching the EI-MS spectral database, and (iv) retention index (RI) filtering in combination with RI predictions. In this study, the new MS-FINDER spectral search engine was developed and utilized for searching EI-MS databases using mass spectral similarity with the evaluation of false discovery rate. Moreover, in silico derivatization software, MetaboloDerivatizer, was developed to calculate the chemical properties of derivative compounds, and all retention indexes in EI-MS databases were predicted using a simple mathematical model. The strategy was showcased in the identification of three novel metabolites (butane-1,2,3-triol, 3-deoxyglucosone, and palatinitol) in Chinese medicine Senkyu for quality assessment, as validated using authentic standard compounds. All tools and curated public EI-MS databases are freely available in the 'Computational MS-based metabolomics' section of the RIKEN PRIMe website (http://prime.psc.riken.jp). PMID: 28520403 [PubMed - as supplied by publisher]

Integrated metabolomics and metallomics analyses in acute coronary syndrome patients.

Fri, 19/05/2017 - 14:06
Related Articles Integrated metabolomics and metallomics analyses in acute coronary syndrome patients. Metallomics. 2017 May 18;: Authors: Yin X, de Carvalho LP, Chan MY, Li SFY Abstract Acute coronary syndrome (ACS) is the leading cause of morbidity and mortality. Accurate risk prediction in ACS patients is critically important for helping clinicians make therapeutic decisions, such as recommending a more aggressive intervention and intensive follow-up. However, risk stratification in ACS patients remains challenging, and the identification of novel predictors is necessary for improving the prognostic prediction in ACS patients. We employed metallomics and untargeted metabolomics approaches to discover new biomarkers from the plasma samples of 20 ACS patients and 20 non-ACS patients. We identified metabolic changes related to lysophosphatidylcholines, caffeine, glycolysis, tryptophan and sphingomyelin metabolism (p value <0.05) that were perturbed in the ACS patients. Moreover, circulating metal elements, including Mg, Ca, K, Zn, Ni, Ga and In (p value <0.05), were altered in the ACS patients versus the controls. These changes suggest possible changes in cell membrane permeability and rigidity in ACS patients. PMID: 28518204 [PubMed - as supplied by publisher]

Plasma and serum metabolite association networks: comparability within and between studies using NMR and MS profiling.

Fri, 19/05/2017 - 14:06
Related Articles Plasma and serum metabolite association networks: comparability within and between studies using NMR and MS profiling. J Proteome Res. 2017 May 18;: Authors: Suarez-Diez M, Adam J, Adamski J, Chasapi SA, Luchinat C, Peters A, Prehn C, Santucci C, Spyridonidis A, Spyroulias GA, Tenori L, Wang-Sattler R, Saccenti E Abstract Blood is one of the most used biofluids in metabolomics studies and the serum and plasma fractions are routinely used as a proxy for blood itself. Here, we investigated the associations networks of an array of 29 metabolites identified and quantified via NMR in the plasma and serum samples of two cohorts of ~1000 healthy blood donors each. A second study of 377 individuals was used to extract plasma and serum samples from the same individual on which a set of 122 metabolites were detected and quantified using FIA-MS/MS. Four different inference algorithms (ARANCE, CLR, CORR and PCLRC) were used to obtain consensus networks. The plasma and serum networks obtained from different studies showed different topological properties with the serum network being more connected than the plasma network. On a global level, metabolite association networks from plasma and serum fractions obtained from the same blood sample of healthy people show similar topologies, and at a local level, some differences arise like in the case of amino acids. PMID: 28517934 [PubMed - as supplied by publisher]

Metabolomic analysis shows differential hepatic effects of T2 and T3 in rats after short-term feeding with high fat diet.

Fri, 19/05/2017 - 14:06
Related Articles Metabolomic analysis shows differential hepatic effects of T2 and T3 in rats after short-term feeding with high fat diet. Sci Rep. 2017 May 17;7(1):2023 Authors: Iannucci LF, Cioffi F, Senese R, Goglia F, Lanni A, Yen PM, Sinha RA Abstract Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and is often associated with lipotoxic injury, defective mitochondrial function, and insulin resistance. Thyroid hormones (THs) are important regulators of hepatic lipid metabolism. Among the THs, diiodothyronine (T2) and triiodothyronine (T3) have shown promising results in lowering hepatic fat content in various models of NAFLD. In this study, we used a targeted metabolomics approach to investigate the differential effects of T2 and T3 on the early metabolic adaptation in the livers of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible. Our results showed that both T2 and T3 strongly induced autophagy and intra-hepatic acylcarnitine flux but prevented the generation of sphingolipid/ceramides in animals fed HFD. Interestingly, although both T2 and T3 decreased hepatic fat content, only T2 was able to rescue the impairment in AKT and MAPK/ERK pathways caused by HFD. In summary, we have identified and characterized the effects of T2 and T3 on hepatic metabolism during short-term exposure to HFD. These findings illuminate the common and divergent metabolic pathways by T2 and T3 that also may be important in the prevention and treatment of NAFLD. PMID: 28515456 [PubMed - in process]

Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity.

Fri, 19/05/2017 - 14:06
Related Articles Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity. Proc Natl Acad Sci U S A. 2017 May 17;: Authors: Matsui T, Omuro H, Liu YF, Soya M, Shima T, McEwen BS, Soya H Abstract Brain glycogen stored in astrocytes provides lactate as an energy source to neurons through monocarboxylate transporters (MCTs) to maintain neuronal functions such as hippocampus-regulated memory formation. Although prolonged exhaustive exercise decreases brain glycogen, the role of this decrease and lactate transport in the exercising brain remains less clear. Because muscle glycogen fuels exercising muscles, we hypothesized that astrocytic glycogen plays an energetic role in the prolonged-exercising brain to maintain endurance capacity through lactate transport. To test this hypothesis, we used a rat model of exhaustive exercise and capillary electrophoresis-mass spectrometry-based metabolomics to observe comprehensive energetics of the brain (cortex and hippocampus) and muscle (plantaris). At exhaustion, muscle glycogen was depleted but brain glycogen was only decreased. The levels of MCT2, which takes up lactate in neurons, increased in the brain, as did muscle MCTs. Metabolomics revealed that brain, but not muscle, ATP was maintained with lactate and other glycogenolytic/glycolytic sources. Intracerebroventricular injection of the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol did not affect peripheral glycemic conditions but suppressed brain lactate production and decreased hippocampal ATP levels at exhaustion. An MCT2 inhibitor, α-cyano-4-hydroxy-cinnamate, triggered a similar response that resulted in lower endurance capacity. These findings provide direct evidence for the energetic role of astrocytic glycogen-derived lactate in the exhaustive-exercising brain, implicating the significance of brain glycogen level in endurance capacity. Glycogen-maintained ATP in the brain is a possible defense mechanism for neurons in the exhausted brain. PMID: 28515312 [PubMed - as supplied by publisher]

Natural mutagenesis-enabled global proteomic study of metabolic and carbon source implications in mutant thermoacidophillic Archaeon Sulfolobus solfataricus PBL2025.

Fri, 19/05/2017 - 14:06
Related Articles Natural mutagenesis-enabled global proteomic study of metabolic and carbon source implications in mutant thermoacidophillic Archaeon Sulfolobus solfataricus PBL2025. J Proteome Res. 2017 May 17;: Authors: Qiu W, Pham TK, Zou X, Ow SY, Wright PC Abstract The thermoacidophilic crenarchaeon Sulfolobus solfataricus has been widely used as a model organism for archaeal systems biology research. Investigation using its spontaneous mutant PBL2025 provides an effective metabolic baseline to study subsequent mutagenesis-induced process shifts as well as changes in feedback inhibitions. Here, an untargeted metabolic investigation using quantitative proteomics and metabolomics was performed to correlate changes in S. solfataricus strains P2 against PBL2025 and under both glucose and tryptone. The study is combined with pathway enrichment analysis to identify prominent proteins with differential stoichiometry. Proteome level quantification reveals that over 20% of the observed overlapping proteome is differentially expressed under these conditions. Metabolic-induced differential expressions are observed along the central carbon metabolism, along with 12 other significantly regulated pathways. Current findings suggest that PBL2025 is able to compensate through the induction of carbon metabolism, as well as other anabolic pathways such as Val, Leu and iso-Leu biosynthesis. Studying protein abundance changes after changes in carbon sources also reveals distinct differences in metabolic strategies employed by both strains, whereby a clear down-regulation of carbohydrate and nucleotide metabolism is observed for P2, while a mixed response through down-regulation of energy formation and up-regulation of glycolysis is observed for PBL2025. This study contributes, to date, the most comprehensive network of changes in carbohydrate and amino acid pathways using the complementary systems biology observations at the protein and metabolite levels. Current findings provide a unique insight into molecular processing changes through natural (spontaneous) metabolic rewiring, as well as a systems biology understanding of the metabolic elasticity of thermoacidophiles to environmental carbon source change; potentially guiding more efficient directed mutagenesis in archaea. PMID: 28514846 [PubMed - as supplied by publisher]

Which Specialized Metabolites Does the Native Subantarctic Gastropod Notodiscus hookeri Extract from the Consumption of the Lichens Usnea taylorii and Pseudocyphellaria crocata?

Fri, 19/05/2017 - 14:06
Related Articles Which Specialized Metabolites Does the Native Subantarctic Gastropod Notodiscus hookeri Extract from the Consumption of the Lichens Usnea taylorii and Pseudocyphellaria crocata? Molecules. 2017 Mar 08;22(3): Authors: Gadea A, Le Pogam P, Biver G, Boustie J, Le Lamer AC, Le Dévéhat F, Charrier M Abstract Notodiscus hookeri is the only representative of terrestrial gastropods on Possession Island and exclusively feeds on lichens. The known toxicity of various lichen metabolites to plant-eating invertebrates led us to propose that N. hookeri evolved means to protect itself from their adverse effects. To validate this assumption, the current study focused on the consumption of two lichen species: Usnea taylorii and Pseudocyphellaria crocata. A controlled feeding experiment was designed to understand how the snail copes with the unpalatable and/or toxic compounds produced by these lichen species. The occurrence of two snail ecophenotypes, represented by a mineral shell and an organic shell, led to address the question of a metabolic response specific to the phenotype. Snails were fed for two months with one of these lichens and the chemical profiles of biological samples of N. hookeri (i.e., crop, digestive gland, intestine, and feces) were established by HPLC-DAD-MS and compared to that of the lichens. N. hookeri appears as a generalist lichen feeder able to consume toxic metabolite-containing lichens, independently of the ecophenotype. The digestive gland did not sequester lichen metabolites. The snail metabolism might be based on four non-exclusive processes according to the concerned metabolites (avoidance, passive transport, hydrolysis, and excretion). PMID: 28282888 [PubMed - indexed for MEDLINE]

Metabolite Profiling of Eastern Teaberry (Gaultheria procumbens L.) Lipophilic Leaf Extracts with Hyaluronidase and Lipoxygenase Inhibitory Activity.

Fri, 19/05/2017 - 14:06
Related Articles Metabolite Profiling of Eastern Teaberry (Gaultheria procumbens L.) Lipophilic Leaf Extracts with Hyaluronidase and Lipoxygenase Inhibitory Activity. Molecules. 2017 Mar 06;22(3): Authors: Michel P, Owczarek A, Matczak M, Kosno M, Szymański P, Mikiciuk-Olasik E, Kilanowicz A, Wesołowski W, Olszewska MA Abstract The phytochemical profile and anti-inflammatory activity of Gaultheria procumbens dry lipophilic leaf extracts were evaluated. Forty compounds were identified by GC-MS, representing 86.36% and 81.97% of the petroleum ether (PE) and chloroform (CHE) extracts, respectively, with ursolic acid (28.82%), oleanolic acid (10.11%), methyl benzoate (10.03%), and methyl salicylate (6.88%) dominating in CHE, and methyl benzoate (21.59%), docosane (18.86%), and octacosane (11.72%) prevailing in PE. Three components of CHE were fully identified after flash chromatography isolation and spectroscopic studies as (6S,9R)-vomifoliol (4.35%), 8-demethyl-latifolin (1.13%), and 8-demethylsideroxylin (2.25%). Hyaluronidase and lipoxygenase inhibitory activity was tested for CHE (IC50 = 282.15 ± 10.38 μg/mL and 899.97 ± 31.17 μg/mL, respectively), PE (IC50 = 401.82 ± 16.12 μg/mL and 738.49 ± 15.92 μg/mL), and nine of the main constituents versus heparin (IC50 = 366.24 ± 14.72 μg/mL) and indomethacin (IC50 = 92.60 ± 3.71 μg/mL) as positive controls. With the best activity/concentration relationships, ursolic and oleanolic acids were recommended as analytical markers for the extracts and plant material. Seasonal variation of both markers following foliar development was investigated by UHPLC-PDA. The highest levels of ursolic (5.36-5.87 mg/g DW of the leaves) and oleanolic (1.14-1.26 mg/g DW) acids were observed between August and October, indicating the optimal season for harvesting. PMID: 28272321 [PubMed - indexed for MEDLINE]

Merkel Cell Polyomavirus Small T Antigen Promotes Pro-Glycolytic Metabolic Perturbations Required for Transformation.

Fri, 19/05/2017 - 14:06
Related Articles Merkel Cell Polyomavirus Small T Antigen Promotes Pro-Glycolytic Metabolic Perturbations Required for Transformation. PLoS Pathog. 2016 Nov;12(11):e1006020 Authors: Berrios C, Padi M, Keibler MA, Park DE, Molla V, Cheng J, Lee SM, Stephanopoulos G, Quackenbush J, DeCaprio JA Abstract Merkel cell polyomavirus (MCPyV) is an etiological agent of Merkel cell carcinoma (MCC), a highly aggressive skin cancer. The MCPyV small tumor antigen (ST) is required for maintenance of MCC and can transform normal cells. To gain insight into cellular perturbations induced by MCPyV ST, we performed transcriptome analysis of normal human fibroblasts with inducible expression of ST. MCPyV ST dynamically alters the cellular transcriptome with increased levels of glycolytic genes, including the monocarboxylate lactate transporter SLC16A1 (MCT1). Extracellular flux analysis revealed increased lactate export reflecting elevated aerobic glycolysis in ST expressing cells. Inhibition of MCT1 activity suppressed the growth of MCC cell lines and impaired MCPyV-dependent transformation of IMR90 cells. Both NF-κB and MYC have been shown to regulate MCT1 expression. While MYC was required for MCT1 induction, MCPyV-induced MCT1 levels decreased following knockdown of the NF-κB subunit RelA, supporting a synergistic activity between MCPyV and MYC in regulating MCT1 levels. Several MCC lines had high levels of MYCL and MYCN but not MYC. Increased levels of MYCL was more effective than MYC or MYCN in increasing extracellular acidification in MCC cells. Our results demonstrate the effects of MCPyV ST on the cellular transcriptome and reveal that transformation is dependent, at least in part, on elevated aerobic glycolysis. PMID: 27880818 [PubMed - indexed for MEDLINE]

Small-molecule pheromones and hormones controlling nematode development.

Thu, 18/05/2017 - 13:40
Related Articles Small-molecule pheromones and hormones controlling nematode development. Nat Chem Biol. 2017 May 17;13(6):577-586 Authors: Butcher RA Abstract The existence of small-molecule signals that influence development in Caenorhabditis elegans has been known for several decades, but only in recent years have the chemical structures of several of these signals been established. The identification of these signals has enabled connections to be made between these small molecules and fundamental signaling pathways in C. elegans that influence not only development but also metabolism, fertility, and lifespan. Spurred by these important discoveries and aided by recent advances in comparative metabolomics and NMR spectroscopy, the field of nematode chemistry has the potential to expand dramatically in the coming years. This Perspective will focus on small-molecule pheromones and hormones that influence developmental events in the nematode life cycle (ascarosides, dafachronic acids, and nemamides), will cover more recent work regarding the biosynthesis of these signals, and will explore how the discovery of these signals is transforming our understanding of nematode development and physiology. PMID: 28514418 [PubMed - in process]

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