PubMed

Related Articles Normalized testosterone glucuronide (TG/AG) as a potential urinary biomarker for highly variable UGT2B17 in children 7 to 18 years. Clin Pharmacol Ther. 2020 Jan 03;: Authors: Zhang H, Basit A, Wolford C, Chen KF, Gaedigk A, Lin YS, Leeder JS, Prasad B Abstract UDP-glucuronosyltransferase 2B17 (UGT2B17) is a highly variable androgen- and drug-metabolizing enzyme. UGT2B17 exhibits a unique ontogeny profile characterized by a dramatic increase in hepatic protein expression from pre-pubertal age to adulthood. Age, sex, copy number variation (CNV), and single nucleotide polymorphisms only explain 26% of variability in protein expression, highlighting the need for a phenotypic biomarker for predicting inter-individual variability in glucuronidation of UGT2B17 substrates. Here we propose testosterone glucuronide (TG) normalized by androsterone glucuronide (TG/AG) as a urinary UGT2B17 biomarker, and examine the associations between urinary TG/AG and age, sex, and CNV. We performed targeted metabolomics of 12 androgen conjugates with LC-MS/MS in 63 pediatric subjects ages 7 to 18 years followed over 7 visits in 3 years. Consistent with the reported developmental trajectory of UGT2B17 protein expression, urinary TG/AG is significantly associated with age, sex, and CNV. In conclusion, TG/AG shows promise as a phenotypic urinary UGT2B17 biomarker. PMID: 31900930 [PubMed - as supplied by publisher]

Related Articles Effects of the entomopathogenic fungus Metarhizium flavoviride on the fat body lipid composition of Zophobas morio larvae (Coleoptera: Tenebrionidae). Naturwissenschaften. 2020 Jan 03;107(1):7 Authors: Gołębiowski M, Urbanek A, Pietrzak A, Naczk AM, Bojke A, Tkaczuk C, Stepnowski P Abstract Insects employ different defense strategies against fungal infections and chemicals. We aimed to identify the lipid compositions of the fat body of Zophobas morio larvae before and after fungal infection with the entomopathogenic fungus Metarhizium flavoviride. We used gas chromatography-mass spectrometry to analyze lipid extracts of the fat body isolated of Z. morio 2, 5, and 7 days after fungal infection (treatment group) and compared it with the lipid extracts in a control group injected with physiological isotonic saline. In all the samples, fatty acids were the most abundant compound found in the fat body extracts, with hexadecanoic acid/C16:0 being the most abundant lipid. However, the types and concentrations of lipids changed after fungal infection, likely as an immune response. The most considerable changes occurred in the concentrations of long-chain fatty acids, i.e., hexadecanoic acid/C16:0, octadecenoic acid/C18:1, and octadecanoic acid/C18:0. Contents of methyl ester increased significantly after infection, but that of other esters, especially octanoic acid decyl ester/OADE, decreased on the 5th day after infection. To the best of our knowledge, this is the first detailed analysis of the changes in the lipid composition of the fat body of Z. morio larvae as a result of fungal infection. Our results suggest that entomopathogenic fungal infection affects the internal lipid composition of insects, potentially as a way of adjusting to such infection. These results can help understand infection processes and defense strategies of insects against fungal infection. Ultimately, they can contribute to the creation of more effective chemicals against pest insects. PMID: 31900598 [PubMed - in process]

Related Articles A variant near DHCR24 associates with microstructural properties of white matter and peripheral lipid metabolism in adolescents. Mol Psychiatry. 2020 Jan 03;: Authors: Sliz E, Shin J, Syme C, Patel Y, Parker N, Richer L, Gaudet D, Bennett S, Paus T, Pausova Z Abstract Visceral adiposity has been associated with altered microstructural properties of white matter in adolescents. Previous evidence suggests that circulating phospholipid PC(16:0/2:0) may mediate this association. To investigate the underlying biology, we performed a genome-wide association study (GWAS) of the shared variance of visceral fat, PC(16:0/2:0), and white matter microstructure in 872 adolescents from the Saguenay Youth Study. We further studied the metabolomic profile of the GWAS-lead variant in 931 adolescents. Visceral fat and white matter microstructure were assessed with magnetic resonance imaging. Circulating metabolites were quantified with serum lipidomics and metabolomics. We identified a genome-wide significant association near DHCR24 (Seladin-1) encoding a cholesterol-synthesizing enzyme (rs588709, p = 3.6 × 10-8); rs588709 was also associated nominally with each of the three traits (white matter microstructure: p = 2.1 × 10-6, PC(16:0/2:0): p = 0.005, visceral fat: p = 0.010). We found that the metabolic profile associated with rs588709 resembled that of a TM6SF2 variant impacting very low-density lipoprotein (VLDL) secretion and was only partially similar to that of a HMGCR variant. This suggests that the effect of rs588709 on VLDL lipids may arise due to altered phospholipid rather than cholesterol metabolism. The rs588709 was also nominally associated with circulating concentrations of omega-3 fatty acids in interaction with visceral fat and PC(16:0/2:0), and these fatty acid measures showed robust associations with white matter microstructure. Overall, the present study provides evidence that the DHCR24 locus may link peripheral metabolism to brain microstructure, an association with implications for cognitive impairment. PMID: 31900429 [PubMed - as supplied by publisher]

Related Articles Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits. Nat Commun. 2020 Jan 03;11(1):15 Authors: Zaghlool SB, Kühnel B, Elhadad MA, Kader S, Halama A, Thareja G, Engelke R, Sarwath H, Al-Dous EK, Mohamoud YA, Meitinger T, Wilson R, Strauch K, Peters A, Mook-Kanamori DO, Graumann J, Malek JA, Gieger C, Waldenberger M, Suhre K Abstract DNA methylation and blood circulating proteins have been associated with many complex disorders, but the underlying disease-causing mechanisms often remain unclear. Here, we report an epigenome-wide association study of 1123 proteins from 944 participants of the KORA population study and replication in a multi-ethnic cohort of 344 individuals. We identify 98 CpG-protein associations (pQTMs) at a stringent Bonferroni level of significance. Overlapping associations with transcriptomics, metabolomics, and clinical endpoints suggest implication of processes related to chronic low-grade inflammation, including a network involving methylation of NLRC5, a regulator of the inflammasome, and associated pQTMs implicating key proteins of the immune system, such as CD48, CD163, CXCL10, CXCL11, LAG3, FCGR3B, and B2M. Our study links DNA methylation to disease endpoints via intermediate proteomics phenotypes and identifies correlative networks that may eventually be targeted in a personalized approach of chronic low-grade inflammation. PMID: 31900413 [PubMed - in process]

Related Articles Tissue-specific analysis of lipid species in Drosophila during overnutrition by UHPLC-MS/MS and MALDI-MSI. J Lipid Res. 2020 Jan 03;: Authors: Tuthill BF, Searcy LA, Yost RA, Musselman LP Abstract Diets high in calories can be used to model metabolic diseases including obesity and its associated comorbidities, in animals.  Drosophila melanogaster fed high-sugar diets exhibit complications of human obesity including hyperglycemia, hyperlipidemia, insulin resistance, cardiomyopathy, increased susceptibility to infection, and reduced longevity. We hypothesize that lipid storage in the high sugar-fed fly's fat body reaches a maximum capacity, resulting in the accumulation of toxic lipids in other tissues, or lipotoxicity.  We took two approaches to characterize tissue-specific lipotoxicity. Ultra-high-performance liquid chromatography- tandem mass spectrometry (UHPLC-MS/MS) and matrix-assisted laser desorption/ionization - mass spectrometry imaging (MALDI-MSI) enabled spatial and temporal localization of lipid species in the fat body, heart, and hemolymph. Substituent chain length was diet-dependent, with fewer odd-chain esterified fatty acids on high sugar diets in all sample types. By contrast, dietary effects on double-bond content differed among organs, consistent with a model where some substituent pools are shared, and others are spatially restricted. Both di- and tri-glycerides increased on high sugar diets in all sample types, similar to observations in obese humans. Interestingly, there were dramatic effects of sugar feeding on lipid ethers, which have not been previously associated with lipotoxicity. Taken together, we have identified candidate endocrine mechanisms and molecular targets that may be involved in metabolic disease and lipotoxicity. PMID: 31900315 [PubMed - as supplied by publisher]

22 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 2020/01/04PubMed 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.

22 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 2020/01/04PubMed 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.

19 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 2020/01/03PubMed 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.

19 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 2020/01/03PubMed 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.

18 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 2020/01/02PubMed 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.

18 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 2020/01/02PubMed 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.

25 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 2020/01/01PubMed 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.

25 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 2020/01/01PubMed 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.

27 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 2019/12/31PubMed 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.

27 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 2019/12/31PubMed 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.

Related Articles Amino acids levels in early pregnancy predict subsequent gestational diabetes. J Diabetes. 2019 Dec 27;: Authors: Jiang R, Wu S, Fang C, Wang C, Yang Y, Liu C, Hu J, Huang Y Abstract BACKGROUND: We aimed to estimate the performance of amino acids levels in predicting the risk of subsequent gestational diabetes mellitus (GDM). METHODS: 431 women at 12-16 weeks of gestation in the Department of Obstetrics and Gynecology of the Second Affiliated Hospital of Soochow University were recruited. High performance liquid chromatography electrospray tandem mass spectrometry was used to measure amino acids levels in maternal blood at 12-16 weeks of gestation. At 24-28 weeks of gestation, all participants were administered a 75 g oral glucose tolerance test for the diagnosis of GDM. RESULTS: Alanine, isoleucine and tyrosine levels in early pregnancy were significantly different between women who developed GDM and those who remained normal glucose tolerant (NGT). Logistic regression showed that after adjustments for age, parity, BMI, family history of diabetes, γ-glutamyltranspeptidase, triglycerides, fasting glucose and fasting insulin levels, alanine (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.05-2.04; P=0.027), isoleucine (OR, 1.48; 95% CI, 1.12-1.96; P=0.0062) and tyrosine (OR, 1.46; 95% CI, 1.07-2.03; P=0.020) levels in early pregnancy were independently associated with subsequent GDM. The addition of isoleucine and tyrosine into the conventional model improved area under curve (AUC) from 0.692 to 0.737 (P=0.036) and significantly increased the net reclassification improvement (NRI, +13.7%, P=0.0025). CONCLUSIONS: The present study suggested that elevated isoleucine, tyrosine and alanine levels were independently and significantly associated with subsequent incidence of GDM. New model including conventional risk factors, isoleucine and tyrosine, in early pregnancy might help physicians identify high risk population of GDM. This article is protected by copyright. All rights reserved. PMID: 31883199 [PubMed - as supplied by publisher]

Related Articles Metabolite, Protein, and Lipid Extraction (MPLEx): A Method that Simultaneously Inactivates Middle East Respiratory Syndrome Coronavirus and Allows Analysis of Multiple Host Cell Components Following Infection. Methods Mol Biol. 2020;2099:173-194 Authors: Nicora CD, Sims AC, Bloodsworth KJ, Kim YM, Moore RJ, Kyle JE, Nakayasu ES, Metz TO Abstract Mass spectrometry (MS)-based, integrated proteomics, metabolomics, and lipidomics (collectively, multi-omics) studies provide a very detailed snapshot of virus-induced changes to the host following infection and can lead to the identification of novel prophylactic and therapeutic targets for preventing or lessening disease severity. Multi-omics studies with Middle East respiratory syndrome coronavirus (MERS-CoV) are challenging as the requirements of biosafety level 3 containment limit the numbers of samples that can be safely managed. To address these issues, the multi-omics sample preparation technique MPLEx (metabolite, protein, and lipid extraction) was developed to partition a single sample into three distinct parts (metabolites, proteins, and lipids) for multi-omics analysis, while simultaneously inactivating MERS-CoV by solubilizing and disrupting the viral envelope and denaturing viral proteins. Here we describe the MPLEx protocol, highlight the step of inactivation, and describe the details of downstream processing, instrumental analysis of the three separate analytes, and their subsequent informatics pipelines. PMID: 31883096 [PubMed - in process]

Related Articles Testing the limits of FT-Raman spectroscopy for wine authentication: Cultivar, geographical origin, vintage and terroir effect influence. Sci Rep. 2019 Dec 27;9(1):19954 Authors: Magdas DA, Cozar BI, Feher I, Guyon F, Dehelean A, Cinta Pinzaru S Abstract FT-Raman spectroscopy represents an environmentally friendly technique, suitable for the analysis of high-water content food matrices, like wines, due to its relatively weak water bending mode in the fingerprint region. Based on metabolomics applied to FT-Raman spectra, this study presents the classifications achieved for a sample set comprising 126 wines, originated from Romania and France, with respect to cultivar, geographical origin and vintage. Cultivar recognition was successfully performed among four varieties (Sauvignon, Riesling, Chardonnay, Pinot Gris) while subtle particularities exiting between the Chardonnay wines, coming from the two countries, because of terroir influences were pointed out. The obtained separations of 100% in both initial and cross-validation procedure for geographical differentiation between the two origin countries, as well as, among the three Romanian areas (Transylvania, Muntenia and Moldova) were also discussed. Apart of this, the limitations and the importance of choosing a meaningful data set, in terms of representativity for each classification criterion, are addressed in the present work. PMID: 31882929 [PubMed - in process]

Related Articles Metabolic GWAS of elite athletes reveals novel genetically-influenced metabolites associated with athletic performance. Sci Rep. 2019 Dec 27;9(1):19889 Authors: Al-Khelaifi F, Diboun I, Donati F, Botrè F, Abraham D, Hingorani A, Albagha O, Georgakopoulos C, Suhre K, Yousri NA, Elrayess MA Abstract Genetic research of elite athletic performance has been hindered by the complex phenotype and the relatively small effect size of the identified genetic variants. The aims of this study were to identify genetic predisposition to elite athletic performance by investigating genetically-influenced metabolites that discriminate elite athletes from non-elite athletes and to identify those associated with endurance sports. By conducting a genome wide association study with high-resolution metabolomics profiling in 490 elite athletes, common variant metabolic quantitative trait loci (mQTLs) were identified and compared with previously identified mQTLs in non-elite athletes. Among the identified mQTLs, those associated with endurance metabolites were determined. Two novel genetic loci in FOLH1 and VNN1 are reported in association with N-acetyl-aspartyl-glutamate and Linoleoyl ethanolamide, respectively. When focusing on endurance metabolites, one novel mQTL linking androstenediol (3alpha, 17alpha) monosulfate and SULT2A1 was identified. Potential interactions between the novel identified mQTLs and exercise are highlighted. This is the first report of common variant mQTLs linked to elite athletic performance and endurance sports with potential applications in biomarker discovery in elite athletic candidates, non-conventional anti-doping analytical approaches and therapeutic strategies. PMID: 31882771 [PubMed - in process]

Related Articles Magnetic resonance microscopy and correlative histopathology of the infarcted heart. Sci Rep. 2019 Dec 27;9(1):20017 Authors: Perez-Terol I, Rios-Navarro C, de Dios E, Morales JM, Gavara J, Perez-Sole N, Diaz A, Minana G, Segura-Sabater R, Bonanad C, Bayés-Genis A, Husser O, Monmeneu JV, Lopez-Lereu MP, Nunez J, Chorro FJ, Ruiz-Sauri A, Bodi V, Monleon D Abstract Delayed enhancement cardiovascular magnetic resonance (MR) is the gold-standard for non-invasive assessment after myocardial infarction (MI). MR microscopy (MRM) provides a level of detail comparable to the macro objective of light microscopy. We used MRM and correlative histopathology to identify infarct and remote tissue in contrast agent-free multi-sequence MRM in swine MI hearts. One control group (n = 3 swine) and two experimental MI groups were formed: 90 min of ischemia followed by 1 week (acute MI = 6 swine) or 1 month (chronic MI = 5 swine) reperfusion. Representative samples of each heart were analysed by contrast agent-free multi-sequence (T1-weighting, T2-weighting, T2*-weighting, T2-mapping, and T2*-mapping). MRM was performed in a 14-Tesla vertical axis imager (Bruker-AVANCE 600 system). Images from MRM and the corresponding histopathological stained samples revealed differences in signal intensities between infarct and remote areas in both MI groups (p-value < 0.001). The multivariable models allowed us to precisely classify regions of interest (acute MI: specificity 92% and sensitivity 80%; chronic MI: specificity 100% and sensitivity 98%). Probabilistic maps based on MRM images clearly delineated the infarcted regions. As a proof of concept, these results illustrate the potential of MRM with correlative histopathology as a platform for exploring novel contrast agent-free MR biomarkers after MI. PMID: 31882712 [PubMed - in process]