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

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 34 min 47 sec ago

Advancing the large-scale CCS database for metabolomics and lipidomics at the machine-learning era.

Wed, 15/11/2017 - 13:48
Advancing the large-scale CCS database for metabolomics and lipidomics at the machine-learning era. Curr Opin Chem Biol. 2017 Nov 11;42:34-41 Authors: Zhou Z, Tu J, Zhu ZJ Abstract Metabolomics and lipidomics aim to comprehensively measure the dynamic changes of all metabolites and lipids that are present in biological systems. The use of ion mobility-mass spectrometry (IM-MS) for metabolomics and lipidomics has facilitated the separation and the identification of metabolites and lipids in complex biological samples. The collision cross-section (CCS) value derived from IM-MS is a valuable physiochemical property for the unambiguous identification of metabolites and lipids. However, CCS values obtained from experimental measurement and computational modeling are limited available, which significantly restricts the application of IM-MS. In this review, we will discuss the recently developed machine-learning based prediction approach, which could efficiently generate precise CCS databases in a large scale. We will also highlight the applications of CCS databases to support metabolomics and lipidomics. PMID: 29136580 [PubMed - as supplied by publisher]

Non-targeted metabolomics-guided sildenafil metabolism study in human liver microsomes.

Wed, 15/11/2017 - 13:48
Non-targeted metabolomics-guided sildenafil metabolism study in human liver microsomes. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Nov 07;1072:86-93 Authors: Kim JH, Jo JH, Seo KA, Hwang H, Lee HS, Lee S Abstract Metabolomics combined with high-resolution mass spectrometry (HR-MS) and multivariate data analysis has broad applications in the study of xenobiotic metabolism. Although information about xenobiotic metabolism is essential to understand toxic mechanisms, pharmacokinetic parameters and excretion pathways, it is limited to predict all generated metabolites in biological fluids. Here, we revisited sildenafil metabolism in human liver microsomes using a metabolomics approach to achieve a global picture of sildenafil phase 1 metabolism. Finally, 12 phase 1 metabolites were identified in human liver microsomes; M1-M5 were previously known metabolites. The chemical structures of the novel metabolites were elucidated by MS(2) fragmentation using an HR-MS system as follows: M6, reduced sildenafil; M7, N,N-deethylation and mono-oxidation; M8, demethanamine, N,N-deethylation and mono-hydroxylation; M9, demethanamine and N,N-deethylation; M10 and M11, mono-oxidation in the piperazine ring after N-demethylation; and M12, mono-oxidation. All metabolites, except M1, were formed by CYP3A4 and CYP3A5. In conclusion, we successfully updated the metabolic pathway of sildenafil in human liver, including 7 novel metabolites using metabolomics combined with HR-MS and multivariate data analysis. PMID: 29136555 [PubMed - as supplied by publisher]

WikiPathways: a multifaceted pathway database bridging metabolomics to other omics research.

Wed, 15/11/2017 - 13:48
WikiPathways: a multifaceted pathway database bridging metabolomics to other omics research. Nucleic Acids Res. 2017 Nov 10;: Authors: Slenter DN, Kutmon M, Hanspers K, Riutta A, Windsor J, Nunes N, Mélius J, Cirillo E, Coort SL, Digles D, Ehrhart F, Giesbertz P, Kalafati M, Martens M, Miller R, Nishida K, Rieswijk L, Waagmeester A, Eijssen LMT, Evelo CT, Pico AR, Willighagen EL Abstract WikiPathways (wikipathways.org) captures the collective knowledge represented in biological pathways. By providing a database in a curated, machine readable way, omics data analysis and visualization is enabled. WikiPathways and other pathway databases are used to analyze experimental data by research groups in many fields. Due to the open and collaborative nature of the WikiPathways platform, our content keeps growing and is getting more accurate, making WikiPathways a reliable and rich pathway database. Previously, however, the focus was primarily on genes and proteins, leaving many metabolites with only limited annotation. Recent curation efforts focused on improving the annotation of metabolism and metabolic pathways by associating unmapped metabolites with database identifiers and providing more detailed interaction knowledge. Here, we report the outcomes of the continued growth and curation efforts, such as a doubling of the number of annotated metabolite nodes in WikiPathways. Furthermore, we introduce an OpenAPI documentation of our web services and the FAIR (Findable, Accessible, Interoperable and Reusable) annotation of resources to increase the interoperability of the knowledge encoded in these pathways and experimental omics data. New search options, monthly downloads, more links to metabolite databases, and new portals make pathway knowledge more effortlessly accessible to individual researchers and research communities. PMID: 29136241 [PubMed - as supplied by publisher]

The microbiome and HIV persistence: implications for viral remission and cure.

Wed, 15/11/2017 - 13:48
The microbiome and HIV persistence: implications for viral remission and cure. Curr Opin HIV AIDS. 2017 Nov 10;: Authors: Koay WLA, Siems LV, Persaud D Abstract PURPOSE OF REVIEW: This article discusses the interaction between HIV infection, the gut microbiome, inflammation and immune activation, and HIV reservoirs, along with interventions to target the microbiome and their implications for HIV remission and cure. RECENT FINDINGS: Most studies show that HIV-infected adults have a gut microbiome associated with decreased bacterial richness and diversity, and associated systemic inflammation and immune activation. A unique set of individuals, elite controllers, who spontaneously control HIV replication, have a similar microbiome to HIV-uninfected individuals. Conversely, exposure to maternal HIV in infants was shown to alter the gut microbiome, even in infants who escaped perinatal infection. Emerging research highlights the importance of the metabolomics and metaproteomics of the gut microbiome, which may have relevance for HIV remission and cure. Together, these studies illustrate the complexity of the relationship between HIV infection, the gut microbiome, and its systemic effects. SUMMARY: Understanding the association of HIV with the microbiome, metabolome, and metaproteome may lead to novel therapies to decrease inflammation and immune activation, and impact HIV reservoir size and vaccine responses. Further research in this area is important to inform HIV remission and cure treatments. PMID: 29135490 [PubMed - as supplied by publisher]

Proteomic and metabolomic characterization of streptozotocin-induced diabetic nephropathy in TIMP3-deficient mice.

Wed, 15/11/2017 - 13:48
Related Articles Proteomic and metabolomic characterization of streptozotocin-induced diabetic nephropathy in TIMP3-deficient mice. Acta Diabetol. 2017 Nov 13;: Authors: Rossi C, Marzano V, Consalvo A, Zucchelli M, Levi Mortera S, Casagrande V, Mavilio M, Sacchetta P, Federici M, Menghini R, Urbani A, Ciavardelli D Abstract AIMS: The tissue inhibitor of metalloproteinase TIMP3 is a stromal protein that restrains the activity of both protease and receptor in the extracellular matrix and has been found to be down-regulated in diabetic nephropathy (DN), the leading cause of end-stage renal disease in developed countries. METHODS: In order to gain deeper insights on the association of loss of TIMP3 and DN, we performed differential proteomic analysis of kidney and blood metabolic profiling of wild-type and Timp3-knockout mice before and after streptozotocin (STZ) treatment, widely used to induce insulin deficiency and hyperglycemia. RESULTS: Kidney proteomic data and blood metabolic profiles suggest significant alterations of peroxisomal and mitochondrial fatty acids β-oxidation in Timp3-knockout mice compared to wild-type mice under basal condition. These alterations were exacerbated in response to STZ treatment. CONCLUSIONS: Proteomic and metabolomic approaches showed that loss of TIMP3 alone or in combination with STZ treatment results in significant alterations of kidney lipid metabolism and peripheral acylcarnitine levels, supporting the idea that loss of TIMP3 may generate a phenotype more prone to DN. PMID: 29134286 [PubMed - as supplied by publisher]

Metabolomics identifies metabolite biomarkers associated with acute rejection after heart transplantation in rats.

Wed, 15/11/2017 - 13:48
Related Articles Metabolomics identifies metabolite biomarkers associated with acute rejection after heart transplantation in rats. Sci Rep. 2017 Nov 13;7(1):15422 Authors: Lin F, Ou Y, Huang CZ, Lin SZ, Ye YB Abstract The aim of this study was to identify metabolite biomarkers associated with acute rejection after heart transplantation in rats using a LC-MS-based metabolomics approach. A model of heterotopic cardiac xenotransplantation was established in rats, with Wistar rats as donors and SD rats as recipients. Blood and cardiac samples were collected from blank control rats (Group A), rats 5 (Group B) and 7 days (Group C) after heart transplantation, and pretreated rats 5 (Group D) and 7 days (Group E) post-transplantation for pathological and metabolomics analyses. We assessed International Society for Heart and Lung Transplantation (ISHLT) grades 0, 3B, 4, 1 and 1 rejection in groups A to E. There were 15 differential metabolites between groups A and B, 14 differential metabolites between groups A and C, and 10 differential metabolites between groups B and C. In addition, four common differential metabolites, including D-tagatose, choline, C16 sphinganine and D-glutamine, were identified between on days 5 and 7 post-transplantation. Our findings demonstrate that the panel of D-tagatose, choline, C16 sphinganine and D-glutamine exhibits a high sensitivity and specificity for the early diagnosis of acute rejection after heart transplantation, and LC-MS-based metabolomics approach has a potential value for screening post-transplantation biomarkers. PMID: 29133921 [PubMed - in process]

Neuronal hyperactivity due to loss of inhibitory tone in APOE4 mice lacking Alzheimer's disease-like pathology.

Wed, 15/11/2017 - 13:48
Related Articles Neuronal hyperactivity due to loss of inhibitory tone in APOE4 mice lacking Alzheimer's disease-like pathology. Nat Commun. 2017 Nov 13;8(1):1464 Authors: Nuriel T, Angulo SL, Khan U, Ashok A, Chen Q, Figueroa HY, Emrani S, Liu L, Herman M, Barrett G, Savage V, Buitrago L, Cepeda-Prado E, Fung C, Goldberg E, Gross SS, Hussaini SA, Moreno H, Small SA, Duff KE Abstract The ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer's disease (AD). However, the reason APOE4 is associated with increased AD risk remains a source of debate. Neuronal hyperactivity is an early phenotype in both AD mouse models and in human AD, which may play a direct role in the pathogenesis of the disease. Here, we have identified an APOE4-associated hyperactivity phenotype in the brains of aged APOE mice using four complimentary techniques-fMRI, in vitro electrophysiology, in vivo electrophysiology, and metabolomics-with the most prominent hyperactivity occurring in the entorhinal cortex. Further analysis revealed that this neuronal hyperactivity is driven by decreased background inhibition caused by reduced responsiveness of excitatory neurons to GABAergic inhibitory inputs. Given the observations of neuronal hyperactivity in prodromal AD, we propose that this APOE4-driven hyperactivity may be a causative factor driving increased risk of AD among APOE4 carriers. PMID: 29133888 [PubMed - in process]

Effects of microgravity on osteoblast mitochondria: a proteomic and metabolomics profile.

Wed, 15/11/2017 - 13:48
Related Articles Effects of microgravity on osteoblast mitochondria: a proteomic and metabolomics profile. Sci Rep. 2017 Nov 13;7(1):15376 Authors: Michaletti A, Gioia M, Tarantino U, Zolla L Abstract The response of human primary osteoblasts exposed to simulated microgravity has been investigated and analysis of metabolomic and proteomic profiles demonstrated a prominent dysregulation of mitochondrion homeostasis. Gravitational unloading treatment induced a decrease in mitochondrial proteins, mainly affecting efficiency of the respiratory chain. Metabolomic analysis revealed that microgravity influenced several metabolic pathways; stimulating glycolysis and the pentose phosphate pathways, while the Krebs cycle was interrupted at succinate-fumarate transformation. Interestingly, proteomic analysis revealed that Complex II of the mitochondrial respiratory chain, which catalyses the biotransformation of this step, was under-represented by 50%. Accordingly, down-regulation of quinones 9 and 10 was measured. Complex III resulted in up-regulation by 60%, while Complex IV was down-regulated by 14%, accompanied by a reduction in proton transport synthesis of ATP. Finally, microgravity treatment induced an oxidative stress response, indicated by significant decreases in oxidised glutathione and antioxidant enzymes. Decrease in malate dehydrogenase induced a reverse in the malate-aspartate shuttle, contributing to dysregulation of ATP synthesis. Beta-oxidation of fatty acids was inhibited, promoting triglyceride production along with a reduction in the glycerol shuttle. Taken together, our findings suggest that microgravity may suppress bone cell functions, impairing mitochondrial energy potential and the energy state of the cell. PMID: 29133864 [PubMed - in process]

Significance estimation for large scale metabolomics annotations by spectral matching.

Wed, 15/11/2017 - 13:48
Related Articles Significance estimation for large scale metabolomics annotations by spectral matching. Nat Commun. 2017 Nov 14;8(1):1494 Authors: Scheubert K, Hufsky F, Petras D, Wang M, Nothias LF, Dührkop K, Bandeira N, Dorrestein PC, Böcker S Abstract The annotation of small molecules in untargeted mass spectrometry relies on the matching of fragment spectra to reference library spectra. While various spectrum-spectrum match scores exist, the field lacks statistical methods for estimating the false discovery rates (FDR) of these annotations. We present empirical Bayes and target-decoy based methods to estimate the false discovery rate (FDR) for 70 public metabolomics data sets. We show that the spectral matching settings need to be adjusted for each project. By adjusting the scoring parameters and thresholds, the number of annotations rose, on average, by +139% (ranging from -92 up to +5705%) when compared with a default parameter set available at GNPS. The FDR estimation methods presented will enable a user to assess the scoring criteria for large scale analysis of mass spectrometry based metabolomics data that has been essential in the advancement of proteomics, transcriptomics, and genomics science. PMID: 29133785 [PubMed - in process]

Bridging the Global Digital Health Divide for Cardiovascular Disease.

Wed, 15/11/2017 - 13:48
Related Articles Bridging the Global Digital Health Divide for Cardiovascular Disease. Circ Cardiovasc Qual Outcomes. 2017 Nov;10(11): Authors: Banerjee A PMID: 29133470 [PubMed - in process]

A proteometabolomic study of Actinidia deliciosa fruit development.

Wed, 15/11/2017 - 13:48
Related Articles A proteometabolomic study of Actinidia deliciosa fruit development. J Proteomics. 2017 Nov 10;: Authors: Salzano AM, Sobolev A, Carbone V, Petriccione M, Renzone G, Capitani D, Vitale M, Minasi P, Pasquariello MS, Novi G, Zambrano N, Scortichini M, Mannina L, Scaloni A PMID: 29133123 [PubMed - as supplied by publisher]

Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals.

Wed, 15/11/2017 - 13:48
Related Articles Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals. Elife. 2017 Nov 14;6: Authors: Kühl I, Miranda M, Atanassov I, Kuznetsova I, Hinze Y, Mourier A, Filipovska A, Larsson NG Abstract Dysfunction of the oxidative phosphorylation (OXPHOS) system is a major cause of human disease and the cellular consequences are highly complex. Here, we present comparative analyses of mitochondrial proteomes, cellular transcriptomes and targeted metabolomics of five knockout mouse strains deficient in essential factors required for mitochondrial DNA gene expression, leading to OXPHOS dysfunction. Moreover, we describe sequential protein changes during post-natal development and progressive OXPHOS dysfunction in time course analyses in control mice and a middle lifespan knockout, respectively. Very unexpectedly, we identify a new response pathway to OXPHOS dysfunction in which the intra-mitochondrial synthesis of coenzyme Q (ubiquinone, Q) and Q levels are profoundly decreased, pointing towards novel possibilities for therapy. Our extensive omics analyses provide a high-quality resource of altered gene expression patterns under severe OXPHOS deficiency comparing several mouse models, that will deepen our understanding, open avenues for research and provide an important reference for diagnosis and treatment. PMID: 29132502 [PubMed - as supplied by publisher]

Metabolomics-based discovery of a metabolite that enhances oligodendrocyte maturation.

Tue, 14/11/2017 - 13:06
Metabolomics-based discovery of a metabolite that enhances oligodendrocyte maturation. Nat Chem Biol. 2017 Nov 13;: Authors: Beyer BA, Fang M, Sadrian B, Montenegro-Burke JR, Plaisted WC, Kok BPC, Saez E, Kondo T, Siuzdak G, Lairson LL Abstract Endogenous metabolites play essential roles in the regulation of cellular identity and activity. Here we have investigated the process of oligodendrocyte precursor cell (OPC) differentiation, a process that becomes limiting during progressive stages of demyelinating diseases, including multiple sclerosis, using mass-spectrometry-based metabolomics. Levels of taurine, an aminosulfonic acid possessing pleotropic biological activities and broad tissue distribution properties, were found to be significantly elevated (∼20-fold) during the course of oligodendrocyte differentiation and maturation. When added exogenously at physiologically relevant concentrations, taurine was found to dramatically enhance the processes of drug-induced in vitro OPC differentiation and maturation. Mechanism of action studies suggest that the oligodendrocyte-differentiation-enhancing activities of taurine are driven primarily by its ability to directly increase available serine pools, which serve as the initial building block required for the synthesis of the glycosphingolipid components of myelin that define the functional oligodendrocyte cell state. PMID: 29131145 [PubMed - as supplied by publisher]

Mass spectrometry-based metabolomics: Targeting the crosstalk between gut microbiota and brain in neurodegenerative disorders.

Tue, 14/11/2017 - 13:06
Mass spectrometry-based metabolomics: Targeting the crosstalk between gut microbiota and brain in neurodegenerative disorders. Mass Spectrom Rev. 2017 Nov 12;: Authors: Luan H, Wang X, Cai Z Abstract Metabolomics seeks to take a "snapshot" in a time of the levels, activities, regulation and interactions of all small molecule metabolites in response to a biological system with genetic or environmental changes. The emerging development in mass spectrometry technologies has shown promise in the discovery and quantitation of neuroactive small molecule metabolites associated with gut microbiota and brain. Significant progress has been made recently in the characterization of intermediate role of small molecule metabolites linked to neural development and neurodegenerative disorder, showing its potential in understanding the crosstalk between gut microbiota and the host brain. More evidence reveals that small molecule metabolites may play a critical role in mediating microbial effects on neurotransmission and disease development. Mass spectrometry-based metabolomics is uniquely suitable for obtaining the metabolic signals in bidirectional communication between gut microbiota and brain. In this review, we summarized major mass spectrometry technologies including liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and imaging mass spectrometry for metabolomics studies of neurodegenerative disorders. We also reviewed the recent advances in the identification of new metabolites by mass spectrometry and metabolic pathways involved in the connection of intestinal microbiota and brain. These metabolic pathways allowed the microbiota to impact the regular function of the brain, which can in turn affect the composition of microbiota via the neurotransmitter substances. The dysfunctional interaction of this crosstalk connects neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and Huntington's disease. The mass spectrometry-based metabolomics analysis provides information for targeting dysfunctional pathways of small molecule metabolites in the development of the neurodegenerative diseases, which may be valuable for the investigation of underlying mechanism of therapeutic strategies. PMID: 29130504 [PubMed - as supplied by publisher]

Combined Metabolomic and Correlation Networks Analyses Reveal Fumarase Insufficiency Altered Amino Acids Metabolism.

Tue, 14/11/2017 - 13:06
Combined Metabolomic and Correlation Networks Analyses Reveal Fumarase Insufficiency Altered Amino Acids Metabolism. Biomed Chromatogr. 2017 Nov 11;: Authors: Hou E, Li X, Liu Z, Zhang F, Tian Z Abstract Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. Fumarase insufficiencies were associated with increased level of fumarate and decreased level of malate and exacerbated salt-induced hypertension. To gain insights into the metabolism profiles that induced by fumarase insufficiency and identify key regulatory metabolites, we applied a GC-MS based metabolomics platform coupled with a network approach to analyze fumarase insufficient HUVEC cells and negative controls. A total of 24 altered metabolites involved in 7 metabolic pathways were identified as significantly altered, and enriched for the biological module of amino acids metabolism. In addition, Pearson correlation network analysis revealed that fumaric acid, L-malic acid, L-aspartic acid, glycine and L-glutamic acid were hub metabolites according to Pagerank based on their three centrality indices. ALT and GDH activities increased significantly in fumarase deficiency HUVEC cells. These results confirmed that fumarase insufficiency altered amino acid metabolism. The combination of metabolomics and network methods would provide another perspective on expounding the molecular mechanism at metabolomics level. PMID: 29130499 [PubMed - as supplied by publisher]

Nitrogen mustard-induced corneal injury involves the sphingomyelin-ceramide pathway.

Tue, 14/11/2017 - 13:06
Related Articles Nitrogen mustard-induced corneal injury involves the sphingomyelin-ceramide pathway. Ocul Surf. 2017 Nov 09;: Authors: Charkoftaki G, Jester J, Thompson D, Vasiliou V Abstract PURPOSE: Nitrogen mustard (NM), which simulates the effects of sulfur mustard (SM), is a potent vesicant known to cause irreversible corneal damage. This study investigates the mechanisms by which NM induces corneal damage by examining the impact of NM exposure on the morphology and lipidome of the cornea. METHODS: Intact ex vivo rabbit eyes were placed in serum-free DMEM organ culture. NM (0, 1, 2.5, 5 or 10 mg/ml) was applied to the central cornea for 5, 10 or 15 min using a 5 mm filter disk and subsequently rinsed with DMEM. Corneas were then cultured for 3, 24, or 48 h before being fixed for morphological analysis or for 24 h before being snap- frozen for lipidomic analysis. RESULTS: No morphological changes were detected 3 h after NM exposure. Twenty-four h after exposure, 1 mg/ml NM caused erosion of the corneal epithelium, but no damage to the underlying stroma. Damage caused by 2.5 mg/ml NM extended almost two thirds through the corneal stroma, while 5 mg/ml completely penetrated the corneal stroma. Analtered lipid profile occurred 24 h after corneas were exposed to NM. Specific sphingomyelins, ceramides, and diacylglycerols were increased up to 9-, 60- and 10-fold, respectively. CONCLUSIONS: NM induces concentration- and exposure time-dependent damage to the cornea that increases in severity over time. Alterations in the sphingomyelin-ceramidepathway may contribute to the damaging effects of NM exposure. PMID: 29129753 [PubMed - as supplied by publisher]

MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD(+) consumption.

Tue, 14/11/2017 - 13:06
Related Articles MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD(+) consumption. Nat Struct Mol Biol. 2017 Nov;24(11):902-910 Authors: Marjanović MP, Hurtado-Bagès S, Lassi M, Valero V, Malinverni R, Delage H, Navarro M, Corujo D, Guberovic I, Douet J, Gama-Perez P, Garcia-Roves PM, Ahel I, Ladurner AG, Yanes O, Bouvet P, Suelves M, Teperino R, Pospisilik JA, Buschbeck M Abstract Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD(+)-derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing, and that myotubes that lack macroH2A1.1 have a defect in mitochondrial respiratory capacity. We found that the metabolite-binding macrodomain was essential for sustained optimal mitochondrial function but dispensable for gene regulation. Through direct binding, macroH2A1.1 inhibits basal poly-ADP ribose polymerase 1 (PARP-1) activity and thus reduces nuclear NAD(+) consumption. The resultant accumulation of the NAD(+) precursor NMN allows for maintenance of mitochondrial NAD(+) pools that are critical for respiration. Our data indicate that macroH2A1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD(+) consumption and establishing a buffer of NAD(+) precursors in differentiated cells. PMID: 28991266 [PubMed - indexed for MEDLINE]

Volatile organic compounds in gastrointestinal stromal tumour tissue originating from patient-derived xenografts.

Tue, 14/11/2017 - 13:06
Related Articles Volatile organic compounds in gastrointestinal stromal tumour tissue originating from patient-derived xenografts. J Breath Res. 2017 Jun 29;11(3):037101 Authors: Wawrzyniak R, Woźniak A, Gebreyohannes YK, Dykcik B, Schöffski P, Markuszewski MJ Abstract Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and localize mainly in the stomach or small intestine. The metabolomic signatures of GISTs driven by different KIT gene mutations remain undiscovered and unexplored. The main aim of this pilot study was to determine and compare metabolomic profiles in GIST xenograft models with different genetic backgrounds. Metabolomic profiling using gas chromatography coupled with mass spectrometry followed by univariate and multivariate statistical analyses was applied to select metabolites that differentiated the GIST models studied. The significant differences observed in the metabolites were mainly derived from glycolysis, the citric acid cycle and glutamine and lipid metabolism. The obtained results may suggest variable metabolomic signatures of tumours, possibly related to the different underlying, specific KIT gene mutations and with potential implications for the biological behaviour and natural course of this rare disease. This study constitutes a proof of concept in GISTs and reveals the potential of the metabolomic approach in orphan malignancies. PMID: 28416775 [PubMed - indexed for MEDLINE]

Traditional and novel tools to probe the mitochondrial metabolism in health and disease.

Tue, 14/11/2017 - 13:06
Related Articles Traditional and novel tools to probe the mitochondrial metabolism in health and disease. Wiley Interdiscip Rev Syst Biol Med. 2017 Mar;9(2): Authors: Zhang Y, Avalos JL Abstract Mitochondrial metabolism links energy production to other essential cellular processes such as signaling, cellular differentiation, and apoptosis. In addition to producing adenosine triphosphate (ATP) as an energy source, mitochondria are responsible for the synthesis of a myriad of important metabolites and cofactors such as tetrahydrofolate, α-ketoacids, steroids, aminolevulinic acid, biotin, lipoic acid, acetyl-CoA, iron-sulfur clusters, heme, and ubiquinone. Furthermore, mitochondria and their metabolism have been implicated in aging and several human diseases, including inherited mitochondrial disorders, cardiac dysfunction, heart failure, neurodegenerative diseases, diabetes, and cancer. Therefore, there is great interest in understanding mitochondrial metabolism and the complex relationship it has with other cellular processes. A large number of studies on mitochondrial metabolism have been conducted in the last 50 years, taking a broad range of approaches. In this review, we summarize and discuss the most commonly used tools that have been used to study different aspects of the metabolism of mitochondria: ranging from dyes that monitor changes in the mitochondrial membrane potential and pharmacological tools to study respiration or ATP synthesis, to more modern tools such as genetically encoded biosensors and trans-omic approaches enabled by recent advances in mass spectrometry, computation, and other technologies. These tools have allowed the large number of studies that have shaped our current understanding of mitochondrial metabolism. WIREs Syst Biol Med 2017, 9:e1373. doi: 10.1002/wsbm.1373 For further resources related to this article, please visit the WIREs website. PMID: 28067471 [PubMed - indexed for MEDLINE]

Forthcoming Challenges in Mycotoxins Toxicology Research for Safer Food-A Need for Multi-Omics Approach.

Tue, 14/11/2017 - 13:06
Related Articles Forthcoming Challenges in Mycotoxins Toxicology Research for Safer Food-A Need for Multi-Omics Approach. Toxins (Basel). 2017 Jan 04;9(1): Authors: Dellafiora L, Dall'Asta C Abstract The presence of mycotoxins in food represents a severe threat for public health and welfare, and poses relevant research challenges in the food toxicology field. Nowadays, food toxicologists have to provide answers to food-related toxicological issues, but at the same time they should provide the appropriate knowledge in background to effectively support the evidence-based decision-making in food safety. Therefore, keeping in mind that regulatory actions should be based on sound scientific findings, the present opinion addresses the main challenges in providing reliable data for supporting the risk assessment of foodborne mycotoxins. PMID: 28054977 [PubMed - indexed for MEDLINE]

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