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

A post-translational modification of human Norovirus capsid protein attenuates glycan binding.

Fri, 05/04/2019 - 14:12
Related Articles A post-translational modification of human Norovirus capsid protein attenuates glycan binding. Nat Commun. 2019 03 21;10(1):1320 Authors: Mallagaray A, Creutznacher R, Dülfer J, Mayer PHO, Grimm LL, Orduña JM, Trabjerg E, Stehle T, Rand KD, Blaum BS, Uetrecht C, Peters T Abstract Attachment of human noroviruses to histo blood group antigens (HBGAs) is essential for infection, but how this binding event promotes the infection of host cells is unknown. Here, we employ protein NMR experiments supported by mass spectrometry and crystallography to study HBGA binding to the P-domain of a prevalent virus strain (GII.4). We report a highly selective transformation of asparagine 373, located in an antigenic loop adjoining the HBGA binding site, into an iso-aspartate residue. This spontaneous post-translational modification (PTM) proceeds with an estimated half-life of a few days at physiological temperatures, independent of the presence of HBGAs but dramatically affecting HBGA recognition. Sequence conservation and the surface-exposed position of this PTM suggest an important role in infection and immune recognition for many norovirus strains. PMID: 30899001 [PubMed - indexed for MEDLINE]

Development of an adaptable headspace sampling method for metabolic profiling of the fungal volatome.

Fri, 05/04/2019 - 14:12
Related Articles Development of an adaptable headspace sampling method for metabolic profiling of the fungal volatome. Analyst. 2018 Aug 20;143(17):4155-4162 Authors: Ahmed WM, Geranios P, White IR, Lawal O, Nijsen TM, Bromley MJ, Goodacre R, Read ND, Fowler SJ Abstract Pulmonary aspergillosis can cause serious complications in people with a suppressed immune system. Volatile metabolites emitted by Aspergillus spp. have shown promise for early detection of pathogenicity. However, volatile profiles require further research, as effective headspace analysis methods are required for extended chemical coverage of the volatome; in terms of both very volatile and semi-volatile compounds. In this study, we describe a novel adaptable sampling method in which fungal headspace samples can be sampled continuously throughout a defined time period using both active (pumped) and passive (diffusive) methods, with the capability for samples to be stored for later off-line analysis. For this method we utilise thermal desorption-gas chromatography-mass spectrometry to generate volatile metabolic profiles using Aspergillus fumigatus as the model organism. Several known fungal-specific volatiles associated with secondary metabolite biosynthesis (including α-pinene, camphene, limonene, and several sesquiterpenes) were identified. A comparison between the wild-type A. fumigatus with a phosphopantetheinyl transferase null mutant strain (ΔpptA) that is compromised in secondary metabolite synthesis, revealed reduced production of sesquiterpenes. We also showed the lack of terpene compounds production during the early growth phase, whilst pyrazines were identified in both early and late growth phases. We have demonstrated that the fungal volatome is dynamic and it is therefore critically necessary to sample the headspace across several time periods using a combination of active and passive sampling techniques to analyse and understand this dynamism. PMID: 30069568 [PubMed - indexed for MEDLINE]

Comprehensive Tandem-Mass-Spectrometry Coverage of Complex Samples Enabled by Data-Set-Dependent Acquisition.

Fri, 05/04/2019 - 14:12
Related Articles Comprehensive Tandem-Mass-Spectrometry Coverage of Complex Samples Enabled by Data-Set-Dependent Acquisition. Anal Chem. 2018 07 03;90(13):8020-8027 Authors: Broeckling CD, Hoyes E, Richardson K, Brown JM, Prenni JE Abstract Tandem mass spectrometry (MS/MS) is an invaluable experimental tool for providing analytical data supporting the identification of small molecules and peptides in mass-spectrometry-based "omics" experiments. Data-dependent MS/MS (DDA) is a real-time MS/MS-acquisition strategy that is responsive to the signals detected in a given sample. However, in analysis of even moderately complex samples with state-of-the-art instrumentation, the speed of MS/MS acquisition is insufficient to offer comprehensive MS/MS coverage of all detected molecules. Data-independent approaches (DIA) offer greater MS/MS coverage, typically at the expense of selectivity or sensitivity. This report describes data-set-dependent MS/MS (DsDA), a novel integration of MS1-data processing and target prioritization to enable comprehensive MS/MS sampling during the initial MS-level experiment. This approach is guided by the premise that in omics experiments, individual injections are typically made as part of a larger set of samples, and feedback between data processing and data acquisition can allow approximately real-time optimization of MS/MS-acquisition parameters and nearly complete MS/MS-sampling coverage. Using a combination of R, Proteowizard, XCMS, and WRENS software, this concept was implemented on a liquid-chromatograph-coupled quadrupole time-of-flight mass spectrometer. The results illustrate comprehensive MS/MS coverage for a set of complex small-molecule samples and demonstrate a strong improvement on traditional DDA. PMID: 29846054 [PubMed - indexed for MEDLINE]

Nano-LC/NSI MS Refines Lipidomics by Enhancing Lipid Coverage, Measurement Sensitivity, and Linear Dynamic Range.

Fri, 05/04/2019 - 14:12
Related Articles Nano-LC/NSI MS Refines Lipidomics by Enhancing Lipid Coverage, Measurement Sensitivity, and Linear Dynamic Range. Anal Chem. 2018 07 03;90(13):8093-8101 Authors: Danne-Rasche N, Coman C, Ahrends R Abstract Nano-liquid chromatography (nLC)-nanoelectrospray (NSI) is one of the cornerstones of mass-spectrometry-based bioanalytics. Nevertheless, the application of nLC is not yet prevalent in lipid analyses. In this study, we established a reproducible nLC separation for global lipidomics and describe the merits of using such a miniaturized system for lipid analyses. In order to enable comprehensive lipid analyses that is not restricted to specific lipid classes, we particularly optimized sample preparation conditions and reversed-phase separation parameters. We further benchmarked the developed nLC system to a commonly used high flow HPLC/ESI MS system in terms of lipidome coverage and sensitivity. The comparison revealed an intensity gain between 2 and 3 orders of magnitude for individual lipid classes and an increase in the linear dynamic range of up to 2 orders of magnitude. Furthermore, the analysis of the yeast lipidome using nLC/NSI resulted in more than a 3-fold gain in lipid identifications. All in all, we identified 447 lipids from the core phospholipid lipid classes (PA, PE, PC, PS, PG, and PI) in Saccharomyces cerevisiae. PMID: 29792796 [PubMed - indexed for MEDLINE]

metabolomics; +29 new citations

Thu, 04/04/2019 - 13:54
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 2019/04/04PubMed 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.

Multi-Omics Approach: New Potential Key Mechanisms Implicated in Cardiorenal Syndromes.

Wed, 03/04/2019 - 13:37
Related Articles Multi-Omics Approach: New Potential Key Mechanisms Implicated in Cardiorenal Syndromes. Cardiorenal Med. 2019 Apr 02;9(4):201-211 Authors: Virzì GM, Clementi A, Battaglia GG, Ronco C Abstract Cardiorenal syndromes (CRS) include a scenario of clinical interactions characterized by the heart and kidney dysfunction. The crosstalk between cardiac and renal systems is clearly evidenced but not completely understood. Multi-factorial mechanisms leading to CRS do not involve only hemodynamic parameters. In fact, in recent works on organ crosstalk endothelial injury, the alteration of normal immunologic balance, cell death, inflammatory cascades, cell adhesion molecules, cytokine and chemokine overexpression, neutrophil migration, leukocyte trafficking, caspase-mediated induction of apoptotic mechanisms and oxidative stress has been demonstrated to induce distant organ dysfunction. Furthermore, new alternative mechanisms using the multi-omics approach may be implicated in the pathogenesis of cardiorenal crosstalk. The study of "omics" modifications in the setting of cardiovascular and renal disease represents an emerging area of research. Over the last years, indeed, many studies have elucidated the exact mechanisms involved in gene expression and regulation, cellular communication and organ crosstalk. In this review, we analyze epigenetics, gene expression, small non-coding RNAs, extracellular vesicles, proteomics, and metabolomics in the setting of CRS. PMID: 30939477 [PubMed - as supplied by publisher]

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis.

Wed, 03/04/2019 - 13:37
Related Articles Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis. FASEB J. 2019 Apr 02;:fj201802457RR Authors: Gumucio JP, Qasawa AH, Ferrara PJ, Malik AN, Funai K, McDonagh B, Mendias CL Abstract Myosteatosis is the pathologic accumulation of lipid that can occur in conjunction with atrophy and fibrosis following skeletal muscle injury. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many clinical studies have demonstrated that the degree of lipid infiltration negatively correlates with muscle function and regeneration. Our objective was to determine the pathologic changes that result in lipid accumulation in injured muscle fibers. We used a rat model of rotator cuff injury in this study because the rotator cuff muscle group is particularly prone to the development of myosteatosis after injury. Muscles were collected from uninjured controls or 10, 30, or 60 d after injury and analyzed using a combination of muscle fiber contractility assessments, RNA sequencing, and undirected metabolomics, lipidomics, and proteomics, along with bioinformatics techniques to identify potential pathways and cellular processes that are dysregulated after rotator cuff tear. Bioinformatics analyses indicated that mitochondrial function was likely disrupted after injury. Based on these findings and given the role that mitochondria play in lipid metabolism, we then performed targeted biochemical and imaging studies and determined that mitochondrial dysfunction and reduced fatty acid oxidation likely leads to the accumulation of lipid in myosteatosis.-Gumucio, J. P., Qasawa, A. H., Ferrara, P. J., Malik, A. N., Funai, K., McDonagh, B., Mendias, C. L. Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis. PMID: 30939247 [PubMed - as supplied by publisher]

Loss of the glucocorticoid receptor in zebrafish improves muscle glucose availability and increases growth.

Wed, 03/04/2019 - 13:37
Related Articles Loss of the glucocorticoid receptor in zebrafish improves muscle glucose availability and increases growth. Am J Physiol Endocrinol Metab. 2019 Apr 02;: Authors: Faught E, Vijayan MM Abstract Chronic stress and the associated elevation in corticosteroid levels increase muscle protein catabolism. We hypothesized that the GR-regulated restriction of muscle glucose availability may play a role in the increased protein catabolism during chronic stress. To test this, we generated a ubiquitous GR knockout (GRKO) zebrafish to determine the physiological consequence of glucocorticoid stimulation on muscle metabolism and growth. Adult GRKO zebrafish had higher body mass, and this corresponded with an increased protein and lipid, but not carbohydrate content. GRKO fish were hypercortisolemic, but they elicited a higher cortisol response to an acute stressor. However, the stressor-induced increase in plasma glucose level observed in the wildtype was completely abolished in the GRKO fish. Also, the muscle, but not liver, capacity for glucose uptake was enhanced in the GRKO fish, and this corresponded with a higher hexokinase activity in the mutants. Zebrafish lacking GR also showed a higher capacity for protein synthesis, including increased phosphorylation of eIF4B, higher expression of heat shock protein cognate 70, and total protein content. A chronic fasting stressor reduced body mass and muscle protein content in adult zebrafish, but this decrease was attenuated in the GRKO compared to the wildtype fish. Metabolomics analysis revealed that the free pool of amino acid substrates used for oxidation and gluconeogenesis were lower in the fasted GRKO fish muscle compared to the wildtype. Altogether, chronic stressor-mediated GR signalling limits muscle glucose uptake, and this may play a role in protein catabolism, leading to the growth suppression in fish. PMID: 30939052 [PubMed - as supplied by publisher]

Pharmacomicrobiomics: The holy grail to variability in drug response?

Wed, 03/04/2019 - 13:37
Related Articles Pharmacomicrobiomics: The holy grail to variability in drug response? Clin Pharmacol Ther. 2019 Apr 02;: Authors: Sharma A, Buschmann MM, Gilbert JA Abstract The human body, with 3.0×1013 cells and more than 3.8×1013 microorganisms, has nearly a one-to-one ratio of resident microbes to human cells. Initiatives like the Human Microbiome Project, American Gut, and Flemish Gut have identified associations between microbial taxa and human health. The study of interactions between microbiome and pharmaceutical agents i.e. pharamacomicrobiomics has revealed an instrumental role of the microbiome in modulating drug response that alters the therapeutic outcomes. In this review, we present our current comprehension of the relationship of the microbiome, host biology, and pharmaceutical agents such as cardiovascular drugs, analgesics and chemotherapeutic-agents to human disease and treatment outcomes. We also discuss the significance of studying diet-gene-drug interactions and further address the key challenges associated with pharamacomicrobiomics. Finally, we examine proposed models employing systems biology for the application of pharmacomicrobiomics and other omics data, and provide approaches to elucidate microbiome-drug interactions to improve future translation to personalized medicine. This article is protected by copyright. All rights reserved. PMID: 30937887 [PubMed - as supplied by publisher]

Advances in metabolomics of thyroid cancer diagnosis and metabolic regulation.

Wed, 03/04/2019 - 13:37
Related Articles Advances in metabolomics of thyroid cancer diagnosis and metabolic regulation. Endocrine. 2019 Apr 01;: Authors: Abooshahab R, Gholami M, Sanoie M, Azizi F, Hedayati M Abstract Thyroid cancers (TCs) are the most frequent endocrine malignancy with an unpredictable fast-growing incidence, especially in females all over the world. Fine-needle aspiration biopsy (FNAB) analysis is an accurate diagnostic method for detecting thyroid nodules and classification of TC. Though simplicity, safety, and accuracy of FNAB, 15-30% of cases are indeterminate, and it is not possible to determine the exact cytology of the specimen. This demands the need for innovative methods capable to find crucial biomarkers with adequate sensitivity for diagnosis and prediction in TC researches. Cancer-based metabolomics is a vast emerging field focused on the detection of a large set of metabolites extracted from biofluids or tissues. Using analytical chemistry procedures allows for the potential recognition of cancer-based metabolites for the purposes of advancing the era of personalized medicine. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) coupled with separation techniques e.g., gas chromatography (GC) and liquid chromatography (LC) are the main approaches for metabolic studies in cancers. The immense metabolite profiling has provided a chance to discover novel biomarkers for early detection of thyroid cancer and reduce unnecessary aggressive surgery. In this review, we recapitulate the recent advances and developed methods of diverse metabolomics tools and metabolic phenotypes of thyroid cancer, following a brief discussion of recent challenges in the thyroid cancer diagnosis. PMID: 30937722 [PubMed - as supplied by publisher]

Disturbed energy and amino acid metabolism with their diagnostic potential in mitral valve disease revealed by untargeted plasma metabolic profiling.

Wed, 03/04/2019 - 13:37
Related Articles Disturbed energy and amino acid metabolism with their diagnostic potential in mitral valve disease revealed by untargeted plasma metabolic profiling. Metabolomics. 2019 Apr 01;15(4):57 Authors: Jiang L, Wang J, Li R, Fang ZM, Zhu XH, Yi X, Lan H, Wei X, Jiang DS Abstract INTRODUCTION: Mitral valve disease (MVD), including mitral valve regurgitation (MR) and mitral valve stenosis (MS), is a chronic and progressive cardiac malady. However, the metabolic alterations in MVD is not well-understood till now. The current gold standard diagnostic test, transthoracic echocardiography, has limitations on high-throughput measurement and lacks molecular information for early diagnosis of the disease. OBJECTIVE: The present study aimed to investigate the biochemical alterations and to explore their diagnostic potential for MVD. METHODS: Plasma metabolic profile derangements and their diagnostic potential were non-invasively explored in 34 MR and 20 MS patients against their corresponding controls, using high-throughput NMR-based untargeted metabolomics. RESULTS: Eighteen differential metabolites were identified for MR and MS patients respectively, on the basis of multivariate and univariate data analysis, which were mainly involved in energy metabolism, amino acid metabolism, calcium metabolism and inflammation. These differential metabolites, notably the significantly down-regulated formate and lactate, showed high diagnostic potential for MVD by using Spearman's rank-order correlation analysis and ROC analysis. CONCLUSIONS: To the best of our knowledge, the present study is the first one that explores the metabolic derangements and their diagnostic values in MVD patients using metabolomics. The findings indicated that metabolic disturbance occurred in MVD patients, with plasma formate and lactate emerged as important candidate biomarkers for MVD. PMID: 30937548 [PubMed - in process]

Gut microbial dysbiosis is associated with allergen-specific IgE responses in young children with airway allergies.

Wed, 03/04/2019 - 13:37
Related Articles Gut microbial dysbiosis is associated with allergen-specific IgE responses in young children with airway allergies. World Allergy Organ J. 2019;12(3):100021 Authors: Chiu CY, Chan YL, Tsai MH, Wang CJ, Chiang MH, Chiu CC Abstract Background: There is increasing evidence linking alterations of the gut microbial composition during early infancy to the development of atopic diseases and asthma. However, few studies have addressed the association of dysbiotic gut microbiota with allergic reactions through evaluation of feces in young children with allergic airway diseases. Methods: We sought to evaluate relationships among gut microbiota, total fecal immunoglobulin E (IgE) levels, serum allergic sensitization, and their relevance to childhood allergic rhinitis and asthma. Microbial composition and diversity were analyzed with Illumina-based 16S rRNA gene sequencing of 89 stool samples collected from children with asthma (n = 35) and allergic rhinitis (n = 28), and from healthy controls (n = 26). Data analysis was performed using Quantitative Insights into Microbial Ecology (QIIME) software. Results: A significantly lower abundance of organisms of the phylum Firmicutes were found in children with asthma and allergic rhinitis than in the healthy controls. Relatively lower Chao1 and Shannon indices were also found in children with allergic airway diseases but without any significant difference. Total fecal IgE levels in early childhood were strongly correlated with serum D. pteronyssinus- and D. farinae-specific IgE but not with food-specific IgE levels. In comparison with healthy controls, the genus Dorea was less abundant and negatively correlated with total fecal IgE levels in children with rhinitis, whereas the genus Clostridium was abundant and positively correlated with fecal IgE levels in children with asthma. Conclusions: An interaction between particular subsets of gut microbial dysbiosis and IgE-mediated responses to allergens may contribute to the susceptibility to allergic rhinitis and asthma in early childhood. PMID: 30937143 [PubMed]

Peripheral transcriptomic biomarkers for early detection of sporadic Alzheimer disease?

Wed, 03/04/2019 - 13:37
Related Articles Peripheral transcriptomic biomarkers for early detection of sporadic Alzheimer disease? Dialogues Clin Neurosci. 2018 Dec;20(4):293-300 Authors: Hadar A, Gurwitz D Abstract Alzheimer disease (AD) is the major epidemic of the 21st century, its prevalence rising along with improved human longevity. Early AD diagnosis is key to successful treatment, as currently available therapeutics only allow small benefits for diagnosed AD patients. By contrast, future therapeutics, including those already in preclinical or clinical trials, are expected to afford neuroprotection prior to widespread brain damage and dementia. Brain imaging technologies are developing as promising tools for early AD diagnostics, yet their high cost limits their utility for screening at-risk populations. Blood or plasma transcriptomics, proteomics, and/or metabolomics may pave the way for cost-effective AD risk screening in middle-aged individuals years ahead of cognitive decline. This notion is exemplified by data mining of blood transcriptomics from a published dataset. Consortia blood sample collection and analysis from large cohorts with mild cognitive impairment followed longitudinally for their cognitive state would allow the development of a reliable and inexpensive early AD screening tool. PMID: 30936769 [PubMed - in process]

Multi-omics analysis unravels a segregated metabolic flux network that tunes co-utilization of sugar and aromatic carbons in Pseudomonas putida.

Wed, 03/04/2019 - 13:37
Related Articles Multi-omics analysis unravels a segregated metabolic flux network that tunes co-utilization of sugar and aromatic carbons in Pseudomonas putida. J Biol Chem. 2019 Apr 01;: Authors: Kukurugya MA, Mendonca CM, Solhtalab M, Wilkes RA, Thannhauser TW, Aristilde L Abstract Pseudomonas species thrive in different nutritional environments and can catabolize divergent carbon substrates. These capabilities have important implications for the role of these species in natural and engineered carbon processing. However, the metabolic phenotypes enabling Pseudomonas to utilize mixed substrates remain poorly understood. Here, we employed a multi-omics approach involving stable isotope tracers, metabolomics, fluxomics, and proteomics in Pseudomonas putida KT2440 to investigate the constitutive metabolic network that achieves co-utilization of glucose and benzoate, respectively a monomer of carbohydrate polymers and a derivative of lignin monomers. Despite near-equal consumption of both substrates, metabolite isotopologues revealed non-uniform assimilation throughout the metabolic network. Gluconeogenic flux of benzoate-derived carbons from the tricarboxylic acid cycle did not reach the upper Embden-Meyerhof-Parnas pathway nor the pentose-phosphate pathway. These latter two pathways were populated exclusively by glucose-derived carbons through a cyclic connection with the Entner-Doudoroff pathway. We integrated the 13C-metabolomics data with physiological parameters for quantitative flux analysis, demonstrating that the metabolic segregation of the substrate carbons optimally sustained biosynthetic flux demands and redox balance. Changes in protein abundance partially predicted the metabolic flux changes in cells grown on the glucose:benzoate mixture versus on glucose alone. Notably, flux magnitude and directionality were also maintained by metabolite levels and regulation of phosphorylation of key metabolic enzymes. These findings provide new insights into the metabolic architecture that affords adaptability of P. putida to divergent carbon substrates and highlight regulatory points at different metabolic nodes that may underlie the high nutritional flexibility of Pseudomonas species. PMID: 30936206 [PubMed - as supplied by publisher]

High Levels of Prebiotic Resistant Starch in Diet Modulate Gene Expression and Metabolomic Profile in Pancreatic Cancer Xenograft Mice.

Wed, 03/04/2019 - 13:37
Related Articles High Levels of Prebiotic Resistant Starch in Diet Modulate Gene Expression and Metabolomic Profile in Pancreatic Cancer Xenograft Mice. Nutrients. 2019 Mar 27;11(4): Authors: Panebianco C, Villani A, Pazienza V Abstract Cancer initiation and protection mainly derives from a systemic metabolic environment regulated by dietary patterns. Less is known about the impact of nutritional interventions in people with a diagnosis of cancer. The aim of our study was to investigate the effect of a diet rich in resistant starch (RS) on cell pathways modulation and metabolomic phenotype in pancreatic cancer xenograft mice. RNA-Seq experiments on tumor tissue showed that 25 genes resulted in dysregulated pancreatic cancer in mice fed with an RS diet, as compared to those fed with control diet. Moreover, in these two different mice groups, six serum metabolites were deregulated as detected by LC⁻MS analysis. A bioinformatic prediction analysis showed the involvement of the differentially expressed genes on insulin receptor signaling, circadian rhythm signaling, and cancer drug resistance among the three top canonical pathways, whilst cell death and survival, gene expression, and neurological disease were among the three top disease and biological functions. These findings shed light on the genomic and metabolic phenotype, contributing to the knowledge of the mechanisms through which RS may act as a potential supportive approach for enhancing the efficacy of existing cancer treatments. PMID: 30934731 [PubMed - in process]

metabolomics; +22 new citations

Tue, 02/04/2019 - 13:14
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 2019/04/02PubMed 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.

Effect of Acute Total Sleep Deprivation on Plasma Melatonin, Cortisol and Metabolite Rhythms in Females.

Mon, 01/04/2019 - 12:53
Effect of Acute Total Sleep Deprivation on Plasma Melatonin, Cortisol and Metabolite Rhythms in Females. Eur J Neurosci. 2019 Mar 30;: Authors: Honma A, Revell VL, Gunn PJ, Davies SK, Middleton B, Raynaud FI, Skene DJ Abstract Disruption to sleep and circadian rhythms can impact on metabolism. The study aimed to investigate the effect of acute sleep deprivation on plasma melatonin, cortisol and metabolites, to increase understanding of the metabolic pathways involved in sleep/wake regulation processes. Twelve healthy young female subjects remained in controlled laboratory conditions for ~92 h with respect to posture, meals and environment light (18:00-23:00 h and 07:00-09:00 h <8 lux; 23:00-07:00 h 0 lux (sleep opportunity) or <8 lux (continuous wakefulness); 09:00-18:00 h ~ 90 lux). Regular blood samples were collected for 70 h for plasma melatonin and cortisol, and targeted liquid chromatography-mass spectrometry metabolomics. Timepoints between 00:00 and 06:00 h for day 1 (baseline sleep), day 2 (sleep deprivation) and day 3 (recovery sleep) were analysed. Cosinor analysis and MetaCycle analysis were performed for detection of rhythmicity. Night time melatonin levels were significantly increased during sleep deprivation and returned to baseline levels during recovery sleep. No significant differences were observed in cortisol levels. Of 130 plasma metabolites quantified, 41 metabolites were significantly altered across the study nights, with the majority decreasing during sleep deprivation, most notably phosphatidylcholines. In cosinor analysis, 58 metabolites maintained their rhythmicity across the study days, with the majority showing a phase advance during acute sleep deprivation. This observation differs to that previously reported for males. Our study is the first of metabolic profiling in females during sleep deprivation and recovery sleep, and offers a novel view of human sleep/wake regulation and sex differences. This article is protected by copyright. All rights reserved. PMID: 30929284 [PubMed - as supplied by publisher]

Metabolic profiling of elite athletes with different cardiovascular demand.

Mon, 01/04/2019 - 12:53
Metabolic profiling of elite athletes with different cardiovascular demand. Scand J Med Sci Sports. 2019 Mar 31;: Authors: Al-Khelaifi F, Donati F, Botrè F, Latiff A, Abraham D, Hingorani A, Georgakopoulos C, Suhre K, Yousri NA, Elrayess MA Abstract Intensive exercise of elite athletes can lead to physiological alterations in the cardiovascular system in response to increased stroke volume and blood pressure, known collectively as cardiovascular demand (CD). This study aims to compare metabolic differences in elite athletes with high versus low/moderate CD and to reveal their underlying metabolic pathways as potential biomarker signatures for assessing health, performance and recovery of elite athletes. Metabolic profiling of serum samples from 495 elite athletes from different sports disciplines (118 high CD and 377 low/moderate CD athletes) was conducted using non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography. Results show that DAGs containing arachidonic were enriched in high CD together with branched chain amino acids, plasminogens, phosphatidylcholines and phosphatidylethanolamines, potentially indicating increased risk of cardiovascular disease in the high CD group. Gamma glutamyl amino acids and glutathione metabolism were increased in low/moderate CD group, suggesting more efficient oxidative stress scavenging mechanisms than the high CD group. This first most comprehensive metabolic profiling of elite athletes provides an evidence that athletes with different CD show a unique metabolic signature that reflects energy generation and oxidative stress and potentially places the high CD group at a higher risk of cardiovascular disease. Further studies are warranted for confirmation and validation of findings in other sport groups in light of potential confounders related to limited available information about participants. This article is protected by copyright. All rights reserved. PMID: 30929282 [PubMed - as supplied by publisher]

Metabolomic characterization of sunflower leaf allows discriminating genotype groups or stress levels with a minimal set of metabolic markers.

Mon, 01/04/2019 - 12:53
Metabolomic characterization of sunflower leaf allows discriminating genotype groups or stress levels with a minimal set of metabolic markers. Metabolomics. 2019 Mar 30;15(4):56 Authors: Fernandez O, Urrutia M, Berton T, Bernillon S, Deborde C, Jacob D, Maucourt M, Maury P, Duruflé H, Gibon Y, Langlade NB, Moing A Abstract INTRODUCTION: Plant and crop metabolomic analyses may be used to study metabolism across genetic and environmental diversity. Complementary analytical strategies are useful for investigating metabolic changes and searching for biomarkers of response or performance. METHODS AND OBJECTIVES: The experimental material consisted in eight sunflower lines with two line status, four restorers (R, used as males) and four maintainers (B, corresponding to females) routinely used for sunflower hybrid varietal production, respectively to complement or maintain the cytoplasmic male sterility PET1. These lines were either irrigated at full soil capacity (WW) or submitted to drought stress (DS). Our aim was to combine targeted and non-targeted metabolomics to characterize sunflower leaf composition in order to investigate the effect of line status genotypes and environmental conditions and to find the best and smallest set of biomarkers for line status and stress response using a custom-made process of variables selection. RESULTS: Five hundred and eighty-eight metabolic variables were measured by using complementary analytical methods such as 1H-NMR, MS-based profiles and targeted analyses of major metabolites. Based on statistical analyses, a limited number of markers were able to separate WW and DS samples in a more discriminant manner than previously published physiological data. Another metabolic marker set was able to discriminate line status. CONCLUSION: This study underlines the potential of metabolic markers for discriminating genotype groups and environmental conditions. Their potential use for prediction is discussed. PMID: 30929085 [PubMed - in process]

Deciphering the intervention mechanism of Taohong Siwu Decoction following the abnormal uterine bleeding rats based on serum metabolic profiles.

Mon, 01/04/2019 - 12:53
Deciphering the intervention mechanism of Taohong Siwu Decoction following the abnormal uterine bleeding rats based on serum metabolic profiles. J Pharm Biomed Anal. 2019 Mar 23;170:204-214 Authors: Zuo C, Zhang Y, Wang J, Han L, Peng C, Peng D Abstract Abnormal uterine bleeding (AUB), one of the most significant characters of incomplete abortion, is a widespread phenomenon in gynecological that put a woman into a terrible physiological and psychological state. Taohong Siwu Decoction (TSD) is a traditional Chinese medicine (TCM) prescriptions which have treated AUB in China for decades. Our previous study elucidated that TSD reduced the volume of uterine bleedings as well as repaired the endometrium. The present study aims to investigate the mechanisms of TSD on AUB based on serum metabolomics. In this study, serum metabolic profile data was collected using ultra high-performance liquid chromatography with ion trap/time-of-flight mass spectrometry and gas chromatography-mass spectrometry. 23 potential biomarkers (urea, serine, L-proline, L-glutamic acid, palmitic acid, l-acetylcarnitine, LysoPC(16:0), LysoPC(20:4), l-proline, linoleic acid, stearic acid, l-isoleucine, phenylalanine, l-tyrosine, Oleic acid, et al) were eventually identified using multivariate statistical analysis (PCA and OPLS-DA) with VIP > 1, P < 0.05. Correlation analysis, fold-change (FC), area under receiver characteristic (ROC), false discovery rate (FDR) were used for data confirmation to ensure the authenticity of the data. The related-metabolic pathway mainly included amino acid metabolism (Phenylalanine, tyrosine, and tryptophan metabolism; Valine, leucine and isoleucine biosynthesis; Arginine and proline metabolism; Glycine, serine and threonine metabolism) and lipid metabolism (linoleic acid metabolism, glycerophospholipid metabolism). The results show that TSD has a favorable therapeutic effect on AUB by adjusting the metabolic disorders, which could provide dietary guidance for the clinic. PMID: 30928896 [PubMed - as supplied by publisher]

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