PubMed

Related Articles The mitochondrial pyruvate carrier mediates high fat diet-induced increases in hepatic TCA cycle capacity. Mol Metab. 2017 11;6(11):1468-1479 Authors: Rauckhorst AJ, Gray LR, Sheldon RD, Fu X, Pewa AD, Feddersen CR, Dupuy AJ, Gibson-Corley KN, Cox JE, Burgess SC, Taylor EB Abstract OBJECTIVE: Excessive hepatic gluconeogenesis is a defining feature of type 2 diabetes (T2D). Most gluconeogenic flux is routed through mitochondria. The mitochondrial pyruvate carrier (MPC) transports pyruvate from the cytosol into the mitochondrial matrix, thereby gating pyruvate-driven gluconeogenesis. Disruption of the hepatocyte MPC attenuates hyperglycemia in mice during high fat diet (HFD)-induced obesity but exerts minimal effects on glycemia in normal chow diet (NCD)-fed conditions. The goal of this investigation was to test whether hepatocyte MPC disruption provides sustained protection from hyperglycemia during long-term HFD and the differential effects of hepatocyte MPC disruption on TCA cycle metabolism in NCD versus HFD conditions. METHOD: We utilized long-term high fat feeding, serial measurements of postabsorptive blood glucose and metabolomic profiling and 13C-lactate/13C-pyruvate tracing to investigate the contribution of the MPC to hyperglycemia and altered hepatic TCA cycle metabolism during HFD-induced obesity. RESULTS: Hepatocyte MPC disruption resulted in long-term attenuation of hyperglycemia induced by HFD. HFD increased hepatic mitochondrial pyruvate utilization and TCA cycle capacity in an MPC-dependent manner. Furthermore, MPC disruption decreased progression of fibrosis and levels of transcript markers of inflammation. CONCLUSIONS: By contributing to chronic hyperglycemia, fibrosis, and TCA cycle expansion, the hepatocyte MPC is a key mediator of the pathophysiology induced in the HFD model of T2D. PMID: 29107293 [PubMed - indexed for MEDLINE]

Related Articles Outer membrane vesicles secreted by pathogenic and nonpathogenic Bacteroides fragilis represent different metabolic activities. Sci Rep. 2017 07 10;7(1):5008 Authors: Zakharzhevskaya NB, Vanyushkina AA, Altukhov IA, Shavarda AL, Butenko IO, Rakitina DV, Nikitina AS, Manolov AI, Egorova AN, Kulikov EE, Vishnyakov IE, Fisunov GY, Govorun VM Abstract Numerous studies are devoted to the intestinal microbiota and intercellular communication maintaining homeostasis. In this regard, vesicles secreted by bacteria represent one of the most popular topics for research. For example, the outer membrane vesicles (OMVs) of Bacteroides fragilis play an important nutritional role with respect to other microorganisms and promote anti-inflammatory effects on immune cells. However, toxigenic B. fragilis (ETBF) contributes to bowel disease, even causing colon cancer. If nontoxigenic B. fragilis (NTBF) vesicles exert a beneficial effect on the intestine, it is likely that ETBF vesicles can be utilized for potential pathogenic implementation. To confirm this possibility, we performed comparative proteomic HPLC-MS/MS analysis of vesicles isolated from ETBF and NTBF. Furthermore, we performed, for the first time, HPLC-MS/MS and GS-MS comparative metabolomic analysis for the vesicles isolated from both strains with subsequent reconstruction of the vesicle metabolic pathways. We utilized fluxomic experiments to validate the reconstructed biochemical reaction activities and finally observed considerable difference in the vesicle proteome and metabolome profiles. Compared with NTBF OMVs, metabolic activity of ETBF OMVs provides their similarity to micro reactors that are likely to be used for long-term persistence and implementing pathogenic potential in the host. PMID: 28694488 [PubMed - indexed for MEDLINE]

Assessment of Risk Factors and Biomarkers Associated With Risk of Cardiovascular Disease Among Women Consuming a Mediterranean Diet. JAMA Netw Open. 2018 Dec 07;1(8):e185708 Authors: Ahmad S, Moorthy MV, Demler OV, Hu FB, Ridker PM, Chasman DI, Mora S Abstract Importance: Higher Mediterranean diet (MED) intake has been associated with lower risk of cardiovascular disease (CVD), but limited data are available about the underlying molecular mechanisms of this inverse disease association in human populations. Objective: To better characterize the relative contribution of traditional and novel factors to the MED-related risk reduction in CVD events in a US population. Design, Setting, and Participants: Using a prospective cohort design, baseline MED intake was assessed in 25 994 initially healthy US women in the Women's Health Study who were followed up to 12 years. Potential mediating effects of a panel of 40 biomarkers were evaluated, including lipids, lipoproteins, apolipoproteins, inflammation, glucose metabolism and insulin resistance, branched-chain amino acids, small-molecule metabolites, and clinical factors. Baseline study information and samples were collected between April 30, 1993, and January 24, 1996. Analyses were conducted between August 1, 2017, and October 30, 2018. Exposures: Intake of MED is a 9-category measure of adherence to a Mediterranean dietary pattern. Participants were categorized into 3 levels based on their adherence to the MED. Main Outcomes and Measures: Incident CVD confirmed through medical records and the proportion of CVD risk reduction explained by mediators. Results: Among 25 994 women (mean [SD] age, 54.7 [7.1] years), those with low, middle, and upper MED intakes composed 39.0%, 36.2%, and 24.8% of the study population and experienced 428 (4.2%), 356 (3.8%), and 246 (3.8%) incident CVD events, respectively. Compared with the reference group who had low MED intake, CVD risk reductions were observed for the middle and upper groups, with respective HRs of 0.77 (95% CI, 0.67-0.90) and 0.72 (95% CI, 0.61-0.86) (P for trend < .001). The largest mediators of the CVD risk reduction of MED intake were biomarkers of inflammation (accounting for 29.2% of the MED-CVD association), glucose metabolism and insulin resistance (27.9%), and body mass index (27.3%), followed by blood pressure (26.6%), traditional lipids (26.0%), high-density lipoprotein measures (24.0%) or very low-density lipoprotein measures (20.8%), with lesser contributions from low-density lipoproteins (13.0%), branched-chain amino acids (13.6%), apolipoproteins (6.5%), or other small-molecule metabolites (5.8%). Conclusions and Relevance: In this study, higher MED intake was associated with approximately one-fourth relative risk reduction in CVD events, which could be explained in part by known risk factors, both traditional and novel. PMID: 30646282 [PubMed - in process]

Daily consumption of orange juice from Citrus sinensis L. Osbeck cv. Cara Cara and cv. Bahia differently affects Gut Microbiota Profiling as unveiled by an integrated meta-omics approach. J Agric Food Chem. 2019 Jan 15;: Authors: Brasili E, Hassimotto NMA, Del Chierico F, Marini F, Quagliarello A, Sciubba F, Miccheli A, Putignani L, Lajolo FM Abstract We have investigated the effect of intake of two different orange juices from Citrus sinensis cv. 'Cara Cara' and cv. 'Bahia' on faecal microbiota and metabolome using an integrated meta-omics approach. Following a randomized cross-over design, healthy subjects daily consumed 500 mL of orange juice from Cara Cara or Bahia juices or an isocaloric control drink. Stools were collected at baseline (T0) and after a week (T7) of intervention. Operational taxonomic units (OTUs) were pyrosequenced targeting 16S rRNA and faecal metabolites were analysed by an untargeted metabolomics approach based on 1H-NMR- Spectroscopy. The major shift observed in microbiota composition after orange juice intake was the increased abundance of a network of Clostridia OTUs from Mogibacteriaceae, Tissierellaceae, Veillonellaceae, Odoribacteraceae and Ruminococcaceae families, whose members were differently affected by Cara Cara or Bahia juice consumption. A core of six metabolites such as inositol, choline, lysine, arginine, urocanic acid and formate significantly increased in Cara Cara compared to Bahia group. PMID: 30644740 [PubMed - as supplied by publisher]

Identification and quantification of (t)RNA modifications in Pseudomonas aeruginosa by liquid chromatography-tandem mass spectrometry. Chembiochem. 2019 Jan 15;: Authors: Grobe S, Doberenz S, Ferreira K, Krueger J, Brönstrup M, Kaever V, Häußler S Abstract Transfer RNA (tRNA) modifications impact the structure and function of tRNAs thus affecting the efficiency and fidelity of translation. In the opportunistic pathogen Pseudomonas aeruginosa translational regulation plays an important but less defined role in the adaptation to changing environments. In this study, we explored tRNA modifications in P. aeruginosa using LC-MS/MS based approaches. Neutral Loss Scan (NLS) demonstrated the potential to identify previously unknown modifications, while Multiple Reaction Monitoring (MRM) can detect modifications with high specificity and sensitivity. In this study, the MRM-based external calibration method allowed for quantification of the 4 canonical and 32 modified ribonucleosides, of which 21 tRNA modifications were quantified in the total tRNA pool of P. aeruginosa PA14. We also purified the single tRNA isoacceptors tRNA-ArgUCU, tRNA-LeuCAA and tRNA-TrpCCA and determined, both qualitatively and quantitatively, their specific modification pattern. Deeper insights into the nature and dynamics of tRNA modifications in P. aeruginosa will pave the way for further studies on posttranscriptional gene regulation as a relatively unexplored molecular mechanism of controlling bacterial pathogenicity and life style. PMID: 30644616 [PubMed - as supplied by publisher]

Human Suicide, Modern Diagnosis Assistance and Magic Bullet Discovery. Cent Nerv Syst Agents Med Chem. 2019 Jan 15;: Authors: Lu DY, Zhu PP, Wu HY, Yarla NS, Xu B, Ding J, Lu TR Abstract Suicide is still a major event of human mortality (2 %) worldwide. However, no magic bullet (high efficacy drug targeting suicide categories >80%) has been developed due to limitation of biological knowledge of suicide events and pharmacological progress. Influenced by complex environmental factors, social-economic conditions, diverse suicidal-associated genes/molecules, drug development grows slowly and narrow-spectra. In search of pharmaceutical options against human suicide, an accelerating pace of transition from psychoanalysis (cognitive, behavior and emotional) into psycho-morphology disciplines (genetics/image) through neurobiology study (neural-transmitter, receptors and different neural-locations) is more potential now. Neural-psychiatric association study may profoundly impact on pharmacotherapy for suicide prevention and therapeutics. Nonetheless, neural biological knowledge and technical advances for etiological complexity of human suicide (a hybrid of genetics, genomics, epigenetics, proteomics, metabolomics, neural/brain image/circuits versus cognitive, behaviors, emotional and social processing ability) don't allow immediate medical fruits in the clinic and high-quality drug developments in pharmaceutical markets. A great deal of neurobiological study may achieve clinical paradigms (modern diagnosis and magic bullet pharmacotherapy). In the future, clinical suicide prediction and therapeutics by new medications may be in full-swing. PMID: 30644350 [PubMed - as supplied by publisher]

Related Articles Metabolic Profile for Prediction of Ischemic Stroke in Chinese Hypertensive Population. J Stroke Cerebrovasc Dis. 2019 Jan 11;: Authors: Guo X, Li Z, Zhou Y, Yu S, Yang H, Zheng L, Liu Y, Sun Y Abstract BACKGROUND: Stroke burden is extremely high in Chinese hypertensive population. Novel biomarkers for cardiovascular diseases can be detected by metabolomic profiling of human fluids. We aim to find a panel of distinctive plasma metabolites for predicting incident ischemic stroke in hypertensive patients. METHODS: This is a nested case-control study from a prospective cohort design. Baseline plasma samples were collected from 66 newly developed ischemic stroke cases and 66 matched controls. Untargeted metabolomics was performed by ultra-high performance liquid chromatography-tandem mass spectrometry, and data were analyzed by multivariate and univariate statistics. RESULTS: Plasma metabolite profiles clearly differed between hypertensive patients with incident ischemic stroke and without. A total of 12 metabolites were screened and identified as potential biomarkers. The altered metabolic pathways included retinol metabolism, sphingolipid metabolism, glycerophospholipid metabolism, lysine degradation, tyrosine metabolism, and tryptophan metabolism. For prediction of hypertensive ischemic stroke, the panel of specific metabolomics-based biomarkers provided area under the curve of 0.848 (95% confidence interval: 0.783-0.913). CONCLUSIONS: Our study identified a metabolic signature of incident ischemic stroke in hypertension. Differences in small-molecule metabolites hold translational value in prediction and provide insights into potential new mechanisms of this condition. PMID: 30642666 [PubMed - as supplied by publisher]

Related Articles Metabolomic Approach in STEMI-Patients Undergoing Left Ventricular Remodeling. Int J Mol Sci. 2019 Jan 12;20(2): Authors: Garcia G, Chao de la Barca JM, Mirebeau-Prunier D, Reynier P, Furber A, Prunier F, Bière L Abstract Left ventricular remodeling (LVR) occurring after ST-segment elevation myocardial infarction (STEMI) is frequent and severe. We present a metabolomic approach as an attempt to reveal unknown biomarkers associated with post-STEMI LVR. Out of 192 consecutive patients with successfully revascularized STEMI, 32 presented LVR and were clinically matched with 32 no-LVR patients. They underwent cardiac magnetic resonance at baseline, three months and 12 months. Blood samples were collected during index hospitalization. Creatine kinase (CK) peak and inflammatory markers were higher for LVR patients compared to no-LVR patients (mean 3466 ± 2211 and 2394 ± 1615 UI/L respectively, p = 0.005 for CK peak; mean 35.9 ± 44.3 vs. 21.7 ± 30.4 mg/L respectively, p = 0.020 for C-reactive protein). Leukocyte and neutrophil counts were also higher for LVR patients (mean 12028 ± 2593/mL vs. 10346 ± 3626/mL respectively, p = 0.028 and mean 9035 ± 3036/mL vs. 7596 ± 3822/mL respectively, p < 0.001). For metabolomic analysis, sphingomyelin C20:2 and symmetrical dimethylarginine were higher for LVR patients, but did not reach significance after the correction for the alpha risk. The metabolomic approach did not discriminate patients with and without LVR. However, common parameters that focus on infarction severity, such as infarct size and inflammatory markers, differed between the groups. PMID: 30642070 [PubMed - in process]

Related Articles Rapid Cerebral Metabolic Shift during Neonatal Sepsis Is Attenuated by Enteral Colostrum Supplementation in Preterm Pigs. Metabolites. 2019 Jan 11;9(1): Authors: Alinaghi M, Jiang PP, Brunse A, Sangild PT, Bertram HC Abstract Sepsis, the clinical manifestation of serious infection, may disturb normal brain development, especially in preterm infants with an immature brain. We hypothesized that neonatal sepsis induces systemic metabolic alterations that rapidly affect metabolic signatures in immature brain and cerebrospinal fluid (CSF). Cesarean-delivered preterm pigs systemically received 10⁸ CFU/kg Staphylococcus epidermidis (SE) and were provided total parenteral nutrition (n = 9) or enteral supplementation with bovine colostrum (n = 10) and compared with uninfected pigs receiving parenteral nutrition (n = 7). Plasma, CSF, and brain tissue samples were collected after 24 h and analyzed by ¹H NMR-based metabolomics. Both plasma and CSF metabolomes revealed SE-induced changes in metabolite levels that reflected a modified energy metabolism. Hence, increased plasma lactate, alanine, and succinate levels, as well as CSF lactate levels, were observed during SE infection (all p < 0.05, ANOVA analysis). Myo-inositol, a glucose derivative known for beneficial effects on lung maturation in preterm infants, was also increased in plasma and CSF following SE infection. Enteral colostrum supplementation attenuated the lactate accumulation in blood and CSF. Bloodstream infection in preterm newborns was found to induce a rapid metabolic shift in both plasma and CSF, which was modulated by colostrum feeding. PMID: 30641988 [PubMed]

Related Articles Metabolomics Profiling Reveals Rehmanniae Radix Preparata Extract Protects against Glucocorticoid-Induced Osteoporosis Mainly via Intervening Steroid Hormone Biosynthesis. Molecules. 2019 Jan 11;24(2): Authors: Xia T, Dong X, Jiang Y, Lin L, Dong Z, Shen Y, Xin H, Zhang Q, Qin L Abstract Rehmanniae Radix Preparata (RR), the dry rhizome of Rehmannia glutinosa Libosch., is a traditional herbal medicine for improving the liver and kidney function. Ample clinical and pharmacological experiments show that RR can prevent post-menopausal osteoporosis and senile osteoporosis. In the present study, in vivo and in vitro experiments, as well as a UHPLC-Q/TOF-MS-based metabolomics study, were used to explore the preventing effect of RR on glucocorticoid-induced osteoporosis (GIOP) and its underlying mechanisms. As a result, RR significantly enhanced bone mineral density (BMD), improved the micro-architecture of trabecular bone, and intervened in biochemical markers of bone metabolism in dexamethasone (DEX)-treated rats. For the in vitro experiment, RR increased the cell proliferation and alkaline phosphatase (ALP) activity, enhanced the extracellular matrix mineralization level, and improved the expression of runt-related transcription factor 2 (RUNX2) and osteopontin (OPN) in DEX-injured osteoblasts. For the metabolomics study, a total of 27 differential metabolites were detected in the DEX group vs. the control group, of which 10 were significantly reversed after RR treatment. These metabolites were majorly involved in steroid hormone biosynthesis, sex steroids regulation, and amino acid metabolism. By metabolic pathway and Western blotting analysis, it was further ascertained that RR protected against DEX-induced bone loss, mainly via interfering steroid hormone biosynthesis, as evidenced by the up-regulation of cytochrome P450 17A1 (CYP17A1) and aromatase (CYP19A1), and the down-regulation of 11β-hydroxysteroid dehydrogenase (HSD11B1). Collectively, these results indicated that RR had a notable preventing effect on GIOP, and the action mechanism might be related to steroid hormone biosynthesis. PMID: 30641909 [PubMed - in process]

Related Articles Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients' Dried Blood Spots and Plasma. Metabolites. 2019 Jan 11;9(1): Authors: Haijes HA, Willemsen M, Van der Ham M, Gerrits J, Pras-Raves ML, Prinsen HCMT, Van Hasselt PM, De Sain-van der Velden MGM, Verhoeven-Duif NM, Jans JJM Abstract In metabolic diagnostics, there is an emerging need for a comprehensive test to acquire a complete view of metabolite status. Here, we describe a non-quantitative direct-infusion high-resolution mass spectrometry (DI-HRMS) based metabolomics method and evaluate the method for both dried blood spots (DBS) and plasma. 110 DBS of 42 patients harboring 23 different inborn errors of metabolism (IEM) and 86 plasma samples of 38 patients harboring 21 different IEM were analyzed using DI-HRMS. A peak calling pipeline developed in R programming language provided Z-scores for ~1875 mass peaks corresponding to ~3835 metabolite annotations (including isomers) per sample. Based on metabolite Z-scores, patients were assigned a 'most probable diagnosis' by an investigator blinded for the known diagnoses of the patients. Based on DBS sample analysis, 37/42 of the patients, corresponding to 22/23 IEM, could be correctly assigned a 'most probable diagnosis'. Plasma sample analysis, resulted in a correct 'most probable diagnosis' in 32/38 of the patients, corresponding to 19/21 IEM. The added clinical value of the method was illustrated by a case wherein DI-HRMS metabolomics aided interpretation of a variant of unknown significance (VUS) identified by whole-exome sequencing. In summary, non-quantitative DI-HRMS metabolomics in DBS and plasma is a very consistent, high-throughput and nonselective method for investigating the metabolome in genetic disease. PMID: 30641898 [PubMed]

Related Articles 1H NMR based serum metabolic profiling reveals differentiating biomarkers in patients with diabetes and diabetes-related complication. Diabetes Metab Syndr. 2019 Jan - Feb;13(1):290-298 Authors: Rawat A, Misra G, Saxena M, Tripathi S, Dubey D, Saxena S, Aggarwal A, Gupta V, Khan MY, Prakash A Abstract BACKGROUND: Diabetes is among the most prevalent diseases worldwide, of all the affected individuals a significant proportion of the population remains undiagnosed due to lack of specific symptoms early in this disorder and inadequate diagnostics. Diabetes and its associated sequela, i.e., comorbidity are associated with microvascular and macrovascular complications. As diabetes is characterized by an altered metabolism of key metabolites and regulatory pathways. Metabolic phenotyping can provide us with a better understanding of the unique set of regulatory perturbations that predispose to diabetes and its associated complication/comorbidities. METHODOLOGY: The present study utilizes the analytical platform NMR spectroscopy coupled with Random Forest statistical analysis to identify the discriminatory metabolites in diabetes (DB = 38) vs. diabetes-related complication (DC = 35) along with the healthy control (HC = 50) subjects. A combined and pairwise analysis was performed to identify the discriminatory metabolites responsible for class separation. The perturbed metabolites were further rigorously validated using t-test, AUROC analysis to examine the statistical significance of the identified metabolites. RESULTS: The DB and DC patients were well discriminated from HC. However, 15 metabolites were found to be significantly perturbed in DC patients compared to DB, the identified panel of metabolites are TCA cycle (succinate, citrate), methylamine metabolism (trimethylamine, methylamine, betaine), -intermediates; energy metabolites (glucose, lactate, pyruvate); and amino acids (valine, arginine, glutamate, methionine, proline, and threonine). CONCLUSION: The 1H NMR metabolomics may prove a promising technique to differentiate and predict diabetes and its complication on their onset or progression by determining the altered levels of the metabolites in serum. PMID: 30641714 [PubMed - in process]

Related Articles Improve your Galaxy text life: The Query Tabular Tool. F1000Res. 2018;7:1604 Authors: Johnson JE, Kumar P, Easterly C, Esler M, Mehta S, Eschenlauer AC, Hegeman AD, Jagtap PD, Griffin TJ Abstract Galaxy provides an accessible platform where multi-step data analysis workflows integrating disparate software can be run, even by researchers with limited programming expertise. Applications of such sophisticated workflows are many, including those which integrate software from different 'omic domains (e.g. genomics, proteomics, metabolomics). In these complex workflows, intermediate outputs are often generated as tabular text files, which must be transformed into customized formats which are compatible with the next software tools in the pipeline. Consequently, many text manipulation steps are added to an already complex workflow, overly complicating the process. In some cases, limitations to existing text manipulation are such that desired analyses can only be carried out using highly sophisticated processing steps beyond the reach of even advanced users and developers. For users with some SQL knowledge, these text operations could be combined into single, concise query on a relational database. As a solution, we have developed the Query Tabular Galaxy tool, which leverages a SQLite database generated from tabular input data. This database can be queried and manipulated to produce transformed and customized tabular outputs compatible with downstream processing steps. Regular expressions can also be utilized for even more sophisticated manipulations, such as find and replace and other filtering actions. Using several Galaxy-based multi-omic workflows as an example, we demonstrate how the Query Tabular tool dramatically streamlines and simplifies the creation of multi-step analyses, efficiently enabling complicated textual manipulations and processing. This tool should find broad utility for users of the Galaxy platform seeking to develop and use sophisticated workflows involving text manipulation on tabular outputs. PMID: 30519459 [PubMed - in process]

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Related Articles Control of IgG glycosylation by in situ and real-time estimation of specific growth rate of CHO cells cultured in bioreactor. Biotechnol Bioeng. 2019 Jan 13;: Authors: Li MY, Ebel B, Blanchard F, Paris C, Guedon E, Marc A Abstract The cell specific growth rate (µ) is a critical process parameter for antibody production processes performed by animal cell cultures, as it describes the cell growth and reflects the cell physiological state. When there are changes in these parameters, which are indicated by variations of µ, the synthesis and the quality of antibodies are often affected. Therefore, it is essential to monitor and control the variations of µ in order to assure the antibody production and achieve high product quality. In this study, a novel approach for on-line estimation of µ was developed based on the Process Analytical Technology (PAT) initiative by using an in situ dielectric spectroscopy. Critical moments, such as significant µ decreases, were successfully detected by this method, in association with changes in cell physiology as well as with an accumulation of non-glycosylated antibodies. Thus, this method was used to perform medium renewals at the appropriate time points, maintaining the values of µ close to its maximum. Using this method, we demonstrated that the physiological state of cells remained stable, the quantity and the glycosylation quality of antibodies were assured at the same time, leading to better process performances compared to the reference feed-harvest cell cultures carried out by using offline nutrient measurements. This article is protected by copyright. All rights reserved. PMID: 30636319 [PubMed - as supplied by publisher]

Related Articles How Histone Deacetylase Inhibitors Alter the Secondary Metabolites of Botryosphaeria mamane, an Endophytic Fungus Isolated from Bixa orellana, L. Chem Biodivers. 2019 Jan 12;: Authors: Triastuti A, Vansteelandt M, Barakat F, Trinel M, Jargeat P, Fabre N, Amasifuen C, Mejia K, Valentin A, Haddad M Abstract Fungi are talented organisms able to produce several natural products with a wide range of structural and pharmacological activities. The conventional fungal cultivation used in laboratories are too poor to mimic the natural habitats of fungi, and this can partially explain why most of the genes responsible for the production of metabolites are transcriptionally silenced. The use of Histone Deacetylase inhibitors (HDACis) to perturb fungal secondary biosynthetic machinery has proven to be an effective approach for discovering new fungal natural products. The present study relates the effects of suberoylanilidehydroxamic acid (SAHA) and valproate sodium (VS) on the metabolome of Botryosphaeria mamane, an endophytic fungus isolated from Bixa orellana. UHPLC-HRMS analysis integrated with four metabolomics tools: MS-DIAL, MS-FINDER, MetaboAnalyst and GNPS molecular networking, was established. This study highlighted that SAHA and VS changed metabolites in B. mamane, causing upregulation and downregulation of metabolites production. In addition, twelve compounds were detected in the extracts as metabolites structurally correlated to SAHA, indicating its important reactivity in the medium or its metabolism by the fungus. An addition of SAHA induced the production of eight metabolites while VS induced only two metabolites undetected in the control strain. This result illustrates the importance of adding HDACis to a fungal culture in order to induce metabolite production. PMID: 30636097 [PubMed - as supplied by publisher]

Related Articles A gene expression map of shoot domains reveals regulatory mechanisms. Nat Commun. 2019 Jan 11;10(1):141 Authors: Tian C, Wang Y, Yu H, He J, Wang J, Shi B, Du Q, Provart NJ, Meyerowitz EM, Jiao Y Abstract Gene regulatory networks control development via domain-specific gene expression. In seed plants, self-renewing stem cells located in the shoot apical meristem (SAM) produce leaves from the SAM peripheral zone. After initiation, leaves develop polarity patterns to form a planar shape. Here we compare translating RNAs among SAM and leaf domains. Using translating ribosome affinity purification and RNA sequencing to quantify gene expression in target domains, we generate a domain-specific translatome map covering representative vegetative stage SAM and leaf domains. We discuss the predicted cellular functions of these domains and provide evidence that dome seemingly unrelated domains, utilize common regulatory modules. Experimental follow up shows that the RABBIT EARS and HANABA TARANU transcription factors have roles in axillary meristem initiation. This dataset provides a community resource for further study of shoot development and response to internal and environmental signals. PMID: 30635575 [PubMed - in process]

Related Articles Recent advances and perspectives of metabolomics-based investigations in Parkinson's disease. Mol Neurodegener. 2019 Jan 11;14(1):3 Authors: Shao Y, Le W Abstract Parkinson's disease (PD) is the second most prevalent neurodegenerative disease of the central nervous system (CNS), which affects mostly older adults. In recent years, the incidence of PD has been dramatically increasing with the aging population expanding. Due to the lack of effective biomarkers, the accurate diagnosis and precise treatment of PD are currently compromised. Notably, metabolites have been considered as the most direct reflection of the physiological and pathological conditions in individuals and represent attractive candidates to provide deep insights into disease phenotypes. By profiling the metabolites in biofluids (cerebrospinal fluid, blood, urine), feces and brain tissues, metabolomics has become a powerful and promising tool to identify novel biomarkers and provide valuable insights into the etiopathogenesis of neurological diseases. In this review, we will summarize the recent advancements of major analytical platforms implemented in metabolomics studies, dedicated to the improvement and extension of metabolome coverage for in-depth biological research. Based on the current metabolomics studies in both clinical populations and experimental PD models, this review will present new findings in metabolomics biomarkers research and abnormal metabolic pathways in PD, and will discuss the correlation between metabolomic changes and clinical conditions of PD. A better understanding of the biological underpinning of PD pathogenesis might offer novel diagnostic, prognostic, and therapeutic approaches to this devastating disease. PMID: 30634989 [PubMed - in process]

Related Articles Association between serum haptoglobin and carotid arterial functions: usefulness of a targeted metabolomics approach. Cardiovasc Diabetol. 2019 Jan 11;18(1):8 Authors: Wang S, Wang J, Zhang R, Zhao A, Zheng X, Yan D, Jiang F, Jia W, Hu C, Jia W Abstract BACKGROUND: Serum haptoglobin (Hp) has been closely associated with cardio-cerebrovascular diseases. We investigated a metabolic profile associated with circulating Hp and carotid arterial functions via a targeted metabolomics approach to provide insight into potential mechanisms. METHODS: A total of 240 participants, including 120 patients with type 2 diabetes mellitus (T2DM) and 120 non-diabetes mellitus (non-DM) subjects were recruited in this study. Targeted metabolic profiles of serum metabolites were determined using an AbsoluteIDQ™ p180 Kit (BIOCRATES Life Sciences AG, Innsbruck, Austria). Ultrasound of the bilateral common carotid artery was used to measure intima-media thickness and inter-adventitial diameter. Serum Hp levels were tested by enzyme-linked immunosorbent assay. RESULTS: Serum Hp levels in T2DM patients and non-DM subjects were 103.40 (72.46, 131.99) mg/dL and 100.20 (53.99, 140.66) mg/dL, respectively. Significant differences of 19 metabolites and 17 metabolites were found among serum Hp tertiles in T2DM patients and non-DM subjects, respectively (P < 0.05). Of these, phosphatidylcholine acyl-alkyl C32:2 (PC ae C32:2) was the common metabolite observed in two populations, which was associated with the serum Hp groups and lipid traits (P < 0.05). Furthermore, the metabolite ratios of two acidic amino acids, including aspartate to PC ae C32:2 (Asp/PC ae C32:2) and glutamate to PC ae C32:2 (Glu/PC ae C32:2) were correlated with serum Hp, carotid arterial functions and other biochemical index in both populations significantly (P < 0.05). CONCLUSIONS: Targeted metabolomics analyses might provide a new insight into the potential mechanisms underlying the association between serum Hp and carotid arterial functions. PMID: 30634984 [PubMed - in process]

Related Articles Recent Advances on Nucleolar Functions in Health and Disease. Arch Iran Med. 2018 Dec 01;21(12):600-607 Authors: Bahadori M, Azizi MH, Dabiri S Abstract The nucleolus is an internuclear organelle without a visible membrane via the light microscope inside the cell nucleus. It is the main site for synthesis of ribosome as a complex machine for coordinating protein production. It forms around a specific chromosomal feature called the nucleolar organizing region (NOR) which possesses numerous ribosomal DNA (rDNA). Although the nucleolus is best known as coordinator of ribosomal biogenesis and protein synthesis, recently, there is exciting awareness both on better understanding of ribosome biogenesis and non-ribosomal nucleolar functions. A great amount of research has clearly indicated that the nucleolus has functional activities in both ribosomal and non-ribosomal conditions such as development, aging, cell cycle, gene stability, lifespan regulation, and progeria. Through recent sophisticated and advanced technologies such as genomics, proteomics, metabolomics, advances of knowledge in RNA species and new approaches in microscopic analysis methods, researchers have shown that perturbation in the nucleolar structure and function (nucleolar stress) have been associated with human diseases including cancer, viral infection, cardiovascular and neurodegenerative diseases. In this review, we discuss the impact of current research providing new information regarding nucleolar roles and functions in some human diseases and aging. PMID: 30634859 [PubMed - in process]