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

Comparative Metabolomic Analyses of Ipomoea lacunosa Biotypes with Contrasting Glyphosate Tolerance Captures Herbicide-Induced Differential Perturbations in Cellular Physiology.

Wed, 27/12/2017 - 12:46
Comparative Metabolomic Analyses of Ipomoea lacunosa Biotypes with Contrasting Glyphosate Tolerance Captures Herbicide-Induced Differential Perturbations in Cellular Physiology. J Agric Food Chem. 2017 Dec 26;: Authors: Maroli AS, Nandula VK, Duke SO, Gerard P, Tharayil N Abstract Glyphosate tolerant Ipomoea lacunosa is emerging as a problematic weed in the southeastern U.S. Metabolomic profiling was conducted to examine the innate physiology and the glyphosate induced perturbations in two biotypes of I. lacunosa (WAS and QUI) that had contrasting glyphosate tolerance. Compared to the QUI, the innate metabolism of the more tolerant WAS-biotype was characterized by a higher abundance of amino acids, and pyruvate; whereas the sugar profile of less tolerant QUI biotype was dominated by the transport sugar sucrose. Glyphosate application (80 g ae/ha) caused similar shikimate accumulation in both biotypes. Compared to less-tolerant QUI, in WAS the content of aromatic amino acids was less affected upon glyphosate treatment, and the content of Ala, Val, Ile and Pro increased. However, the total sugars decreased by ~75% in WAS, compared to ~50% decrease in QUI. Decrease in sugars, accompanied by an increase in amino acids could delay feedback regulation of upstream enzymes in the shikimate acid pathway in WAS, which could contribute to a greater glyphosate tolerance. Our study, through a metabolomics approach, provides complementary data that could be used to elucidate the cellular physiology of herbicide tolerance. PMID: 29278495 [PubMed - as supplied by publisher]

Application of a deep neural network to metabolomics studies and its performance in determining important variables.

Wed, 27/12/2017 - 12:46
Application of a deep neural network to metabolomics studies and its performance in determining important variables. Anal Chem. 2017 Dec 26;: Authors: Date Y, Kikuchi J Abstract Deep neural networks (DNNs), which are kinds of the machine learning approaches, are powerful tools for analyzing big sets of data derived from biological and environmental systems. However, DNNs are not applicable to metabolomics studies because they have difficulty in identifying contribution factors, e.g., biomarkers, in constructed classification and regression models. In this paper, we describe an improved DNN-based analytical approach that incorporates an importance estimation for each variable using a mean decrease accuracy (MDA) calculation, which is based on a permutation algorithm; this approach is called DNN-MDA. The performance of the DNN-MDA approach was evaluated using a data set of metabolic profiles derived from yellowfin goby that lived in various rivers throughout Japan. Its performance was compared with that of conventional multivariate and machine learning methods, and the DNN-MDA approach was found to have the best classification accuracy (97.8%) among the examined methods. In addition to this, the DNN-MDA approach facilitated the identification of important variables such as trimethylamine N-oxide, inosinic acid, and glycine, which were characteristic metabolites that contributed to the discrimination of the geographical differences between fish caught in the Kanto region and those caught in other regions. As a result, the DNN-MDA approach is a useful and powerful tool for determining the geographical origins of specimens and identifying their biomarkers in metabolomics studies that are conducted in biological and environmental systems. PMID: 29278490 [PubMed - as supplied by publisher]

Complete pathway elucidation and heterologous reconstitution of Rhodiola salidroside biosynthesis.

Wed, 27/12/2017 - 12:46
Related Articles Complete pathway elucidation and heterologous reconstitution of Rhodiola salidroside biosynthesis. Mol Plant. 2017 Dec 19;: Authors: Torrens-Spence MP, Pluskal T, Li FS, Carballo V, Weng JK Abstract Salidroside is a bioactive tyrosine-derived phenolic natural product found in medicinal plants under the Rhodiola genus. In addition to their anti-fatigue and anti-anoxia roles in traditional medicine, Rhodiola total extract and salidroside have also displayed medicinal properties as anti-cardiovascular diseases and anti-cancer agents. The resulting surge in global demand of Rhodiola plants and salidroside has driven some species close to extinction. Here, we report the full elucidation of Rhodiola salidroside biosynthetic pathway utilizing the first comprehensive transcriptomics and metabolomics datasets for Rhodiola rosea. Unlike the previously proposed pathway involving separate decarboxylation and deamination enzymatic steps from tyrosine to the key intermediate 4-hydroxyphenylacetaldehyde (4-HPAA), Rhodiola contains a pyridoxal phosphate (PLP)-dependent 4-hydroxyphenylacetaldehyde synthase (4HPAAS) that directly converts tyrosine to 4-HPAA. We further identified genes encoding the subsequent 4-HPAA reductase (4HPAR) and tyrosol:UDP-glucose 8-O-glucosyltransferase (T8GT), respectively, to complete salidroside biosynthesis in Rhodiola. We show that heterologous production of salidroside can be achieved in yeast Saccharomyces cerevisiae as well as in plant Nicotiana benthamiana through transgenic expression of Rhodiola salidroside biosynthetic genes. This study provides new tools for engineering sustainable production of salidroside in heterologous hosts. PMID: 29277428 [PubMed - as supplied by publisher]

Preliminary metabolomics analysis of placenta in maternal obesity.

Wed, 27/12/2017 - 12:46
Related Articles Preliminary metabolomics analysis of placenta in maternal obesity. Placenta. 2018 Jan;61:89-95 Authors: Fattuoni C, Mandò C, Palmas F, Anelli GM, Novielli C, Parejo Laudicina E, Savasi VM, Barberini L, Dessì A, Pintus R, Fanos V, Noto A, Cetin I Abstract INTRODUCTION: Metabolomics identifies phenotypical groups with specific metabolic profiles, being increasingly applied to several pregnancy conditions. This is the first preliminary study analyzing placental metabolomics in normal weight (NW) and obese (OB) pregnancies. METHODS: Twenty NW (18.5 ≤ BMI< 25 kg/m2) and eighteen OB (BMI≥ 30 kg/m2) pregnancies were studied. Placental biopsies were collected at elective caesarean section. Metabolites extraction method was optimized for hydrophilic and lipophilic phases, then analyzed with GC-MS. Univariate and PLS-DA multivariate analysis were applied. RESULTS: Univariate analysis showed increased uracil levels while multivariate PLS-DA analysis revealed lower levels of LC-PUFA derivatives in the lipophilic phase and several metabolites with significantly different levels in the hydrophilic phase of OB vs NW. DISCUSSION: Placental metabolome analysis of obese pregnancies showed differences in metabolites involved in antioxidant defenses, nucleotide production, as well as lipid synthesis and energy production, supporting a shift towards higher placental metabolism. OB placentas also showed a specific fatty acids profile suggesting a disruption of LC-PUFA biomagnification. This study can lay the foundation to further metabolomic placental characterization in maternal obesity. Metabolic signatures in obese placentas may reflect changes occurring in the intrauterine metabolic environment, which may affect the development of adult diseases. PMID: 29277276 [PubMed - in process]

Multi-omic Mitoprotease Profiling Defines a Role for Oct1p in Coenzyme Q Production.

Wed, 27/12/2017 - 12:46
Related Articles Multi-omic Mitoprotease Profiling Defines a Role for Oct1p in Coenzyme Q Production. Mol Cell. 2017 Dec 07;68(5):970-977.e11 Authors: Veling MT, Reidenbach AG, Freiberger EC, Kwiecien NW, Hutchins PD, Drahnak MJ, Jochem A, Ulbrich A, Rush MJP, Russell JD, Coon JJ, Pagliarini DJ Abstract Mitoproteases are becoming recognized as key regulators of diverse mitochondrial functions, although their direct substrates are often difficult to discern. Through multi-omic profiling of diverse Saccharomyces cerevisiae mitoprotease deletion strains, we predicted numerous associations between mitoproteases and distinct mitochondrial processes. These include a strong association between the mitochondrial matrix octapeptidase Oct1p and coenzyme Q (CoQ) biosynthesis-a pathway essential for mitochondrial respiration. Through Edman sequencing and in vitro and in vivo biochemistry, we demonstrated that Oct1p directly processes the N terminus of the CoQ-related methyltransferase, Coq5p, which markedly improves its stability. A single mutation to the Oct1p recognition motif in Coq5p disrupted its processing in vivo, leading to CoQ deficiency and respiratory incompetence. This work defines the Oct1p processing of Coq5p as an essential post-translational event for proper CoQ production. Additionally, our data visualization tool enables efficient exploration of mitoprotease profiles that can serve as the basis for future mechanistic investigations. PMID: 29220658 [PubMed - indexed for MEDLINE]

1HNMR-Based metabolomic profiling method to develop plasma biomarkers for sensitivity to chronic heat stress in growing pigs.

Wed, 27/12/2017 - 12:46
Related Articles 1HNMR-Based metabolomic profiling method to develop plasma biomarkers for sensitivity to chronic heat stress in growing pigs. PLoS One. 2017;12(11):e0188469 Authors: Dou S, Villa-Vialaneix N, Liaubet L, Billon Y, Giorgi M, Gilbert H, Gourdine JL, Riquet J, Renaudeau D Abstract The negative impact of heat stress (HS) on the production performances in pig faming is of particular concern. Novel diagnostic methods are needed to predict the robustness of pigs to HS. Our study aimed to assess the reliability of blood metabolome to predict the sensitivity to chronic HS of 10 F1 (Large White × Creole) sire families (SF) reared in temperate (TEMP) and in tropical (TROP) regions (n = 56±5 offsprings/region/SF). Live body weight (BW) and rectal temperature (RT) were recorded at 23 weeks of age. Average daily feed intake (AFDI) and average daily gain were calculated from weeks 11 to 23 of age, together with feed conversion ratio. Plasma blood metabolome profiles were obtained by Nuclear Magnetic Resonance spectroscopy (1HNMR) from blood samples collected at week 23 in TEMP. The sensitivity to hot climatic conditions of each SF was estimated by computing a composite index of sensitivity (Isens) derived from a linear combination of t statistics applied to familial BW, ADFI and RT in TEMP and TROP climates. A model of prediction of sensitivity was established with sparse Partial Least Square Discriminant Analysis (sPLS-DA) between the two most robust SF (n = 102) and the two most sensitive ones (n = 121) using individual metabolomic profiles measured in TEMP. The sPLS-DA selected 29 buckets that enabled 78% of prediction accuracy by cross-validation. On the basis of this training, we predicted the proportion of sensitive pigs within the 6 remaining families (n = 337). This proportion was defined as the predicted membership of families to the sensitive category. The positive correlation between this proportion and Isens (r = 0.97, P < 0.01) suggests that plasma metabolome can be used to predict the sensitivity of pigs to hot climate. PMID: 29176781 [PubMed - indexed for MEDLINE]

Omega-3 fatty acid epoxides are autocrine mediators that control the magnitude of IgE-mediated mast cell activation.

Wed, 27/12/2017 - 12:46
Related Articles Omega-3 fatty acid epoxides are autocrine mediators that control the magnitude of IgE-mediated mast cell activation. Nat Med. 2017 Nov;23(11):1287-1297 Authors: Shimanaka Y, Kono N, Taketomi Y, Arita M, Okayama Y, Tanaka Y, Nishito Y, Mochizuki T, Kusuhara H, Adibekian A, Cravatt BF, Murakami M, Arai H Abstract Critical to the function of mast cells in immune responses including allergy is their production of lipid mediators, among which only omega-6 (ω-6) arachidonate-derived eicosanoids have been well characterized. Here, by employing comprehensive lipidomics, we identify omega-3 (ω-3) fatty acid epoxides as new mast cell-derived lipid mediators and show that they are produced by PAF-AH2, an oxidized-phospholipid-selective phospholipase A2. Genetic or pharmacological deletion of PAF-AH2 reduced the steady-state production of ω-3 epoxides, leading to attenuated mast cell activation and anaphylaxis following FcɛRI cross-linking. Mechanistically, the ω-3 epoxides promote IgE-mediated activation of mast cells by downregulating Srcin1, a Src-inhibitory protein that counteracts FcɛRI signaling, through a pathway involving PPARg. Thus, the PAF-AH2-ω-3 epoxide-Srcin1 axis presents new potential drug targets for allergic diseases. PMID: 29035365 [PubMed - indexed for MEDLINE]

Discovery of synthesis and secretion of polyol esters of fatty acids by four basidiomycetous yeast species in the order Sporidiobolales.

Wed, 27/12/2017 - 12:46
Related Articles Discovery of synthesis and secretion of polyol esters of fatty acids by four basidiomycetous yeast species in the order Sporidiobolales. J Ind Microbiol Biotechnol. 2017 Jun;44(6):923-936 Authors: Garay LA, Sitepu IR, Cajka T, Fiehn O, Cathcart E, Fry RW, Kanti A, Joko Nugroho A, Faulina SA, Stephanandra S, German JB, Boundy-Mills KL Abstract Polyol esters of fatty acids (PEFA) are amphiphilic glycolipids produced by yeast that could play a role as natural, environmentally friendly biosurfactants. We recently reported discovery of a new PEFA-secreting yeast species, Rhodotorula babjevae, a basidiomycetous yeast to display this behavior, in addition to a few other Rhodotorula yeasts reported on the 1960s. Additional yeast species within the taxonomic order Sporidiobolales were screened for secreted glycolipid production. PEFA production equal or above 1 g L-1 were detected in 19 out of 65 strains of yeast screened, belonging to 6 out of 30 yeast species tested. Four of these species were not previously known to secrete glycolipids. These results significantly increase the number of yeast species known to secrete PEFA, holding promise for expanding knowledge of PEFA synthesis and secretion mechanisms, as well as setting the groundwork towards commercialization. PMID: 28289902 [PubMed - indexed for MEDLINE]

Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy.

Wed, 27/12/2017 - 12:46
Related Articles Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy. Ann Oncol. 2016 Aug;27(8):1482-92 Authors: Pitt JM, Marabelle A, Eggermont A, Soria JC, Kroemer G, Zitvogel L Abstract The tumor microenvironment (TME) is an integral part of cancer. Recognition of the essential nature of the TME in cancer evolution has led to a shift from a tumor cell-centered view of cancer development to the concept of a complex tumor ecosystem that supports tumor growth and metastatic dissemination. Accordingly, novel targets within the TME have been uncovered that can help direct and improve the actions of various cancer therapies, notably immunotherapies that work by potentiating host antitumor immune responses. Here, we review the composition of the TME, how this attenuates immunosurveillance, and discuss existing and potential strategies aimed at targeting cellular and molecular TME components. PMID: 27069014 [PubMed - indexed for MEDLINE]

High resolution metabolomics to determines the risk associated with bisphenol A exposure in humans.

Tue, 26/12/2017 - 12:35
High resolution metabolomics to determines the risk associated with bisphenol A exposure in humans. Environ Toxicol Pharmacol. 2017 Dec 16;58:1-10 Authors: Cho S, Khan A, Jee SH, Lee HS, Hwang MS, Koo YE, Park YH Abstract Although high BPA exposure has been correlated with several metabolic diseases, the underlying mechanisms are unclear. In the present study, a metabolomics approach was used to explore the metabolic variations caused by low or high BPA exposure in female (n = 96) and male (n = 98) urine. Fatty acid elongation and sphingolipid metabolism were affected by high BPA exposure in males and females. Fatty acid elongation and sphingolipid metabolism were further investigated among age groups consisted of 30-39 yrs old, 40-49 yrs old, and 50-59 yrs old males and females with high or low urinary BPA. High BPA-exposed males in 30 s and females in 40 s were found with significant disturbance in fatty acid elongation and sphingolipid metabolism, respectively. Additionally, females in 40 s showed elevated inflammatory metabolites: 6-ketoprostaglandin E1 and thromboxane. In the present study, we have demonstrated that environmental metabolomics is useful to elucidate the health effects of BPA exposure. PMID: 29276974 [PubMed - as supplied by publisher]

SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids.

Tue, 26/12/2017 - 12:35
Related Articles SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids. Clin Mass Spectrom. 2016 Dec;2:1-10 Authors: Zhang X, Romm M, Zheng X, Zink EM, Kim YM, Burnum-Johnson KE, Orton DJ, Apffel A, Ibrahim YM, Monroe ME, Moore RJ, Smith JN, Ma J, Renslow RS, Thomas DG, Blackwell AE, Swinford G, Sausen J, Kurulugama RT, Eno N, Darland E, Stafford G, Fjeldsted J, Metz TO, Teeguarden JG, Smith RD, Baker ES Abstract Characterization of endogenous metabolites and xenobiotics is essential to deconvoluting the genetic and environmental causes of disease. However, surveillance of chemical exposure and disease-related changes in large cohorts requires an analytical platform that offers rapid measurement, high sensitivity, efficient separation, broad dynamic range, and application to an expansive chemical space. Here, we present a novel platform for small molecule analyses that addresses these requirements by combining solid-phase extraction with ion mobility spectrometry and mass spectrometry (SPE-IMS-MS). This platform is capable of performing both targeted and global measurements of endogenous metabolites and xenobiotics in human biofluids with high reproducibility (CV 6 3%), sensitivity (LODs in the pM range in biofluids) and throughput (10-s sample-to-sample duty cycle). We report application of this platform to the analysis of human urine from patients with and without type 1 diabetes, where we observed statistically significant variations in the concentration of disaccharides and previously unreported chemical isomers. This SPE-IMS-MS platform overcomes many of the current challenges of large-scale metabolomic and exposomic analyses and offers a viable option for population and patient cohort screening in an effort to gain insights into disease processes and human environmental chemical exposure. PMID: 29276770 [PubMed]

In Silico Analysis of the Small Molecule Content of Outer Membrane Vesicles Produced by Bacteroides thetaiotaomicron Indicates an Extensive Metabolic Link between Microbe and Host.

Tue, 26/12/2017 - 12:35
Related Articles In Silico Analysis of the Small Molecule Content of Outer Membrane Vesicles Produced by Bacteroides thetaiotaomicron Indicates an Extensive Metabolic Link between Microbe and Host. Front Microbiol. 2017;8:2440 Authors: Bryant WA, Stentz R, Le Gall G, Sternberg MJE, Carding SR, Wilhelm T Abstract The interactions between the gut microbiota and its host are of central importance to the health of the host. Outer membrane vesicles (OMVs) are produced ubiquitously by Gram-negative bacteria including the gut commensal Bacteroides thetaiotaomicron. These vesicles can interact with the host in various ways but until now their complement of small molecules has not been investigated in this context. Using an untargeted high-coverage metabolomic approach we have measured the small molecule content of these vesicles in contrasting in vitro conditions to establish what role these metabolites could perform when packed into these vesicles. B. thetaiotaomicron packs OMVs with a highly conserved core set of small molecules which are strikingly enriched with mouse-digestible metabolites and with metabolites previously shown to be associated with colonization of the murine GIT. By use of an expanded genome-scale metabolic model of B. thetaiotaomicron and a potential host (the mouse) we have established many possible metabolic pathways between the two organisms that were previously unknown, and have found several putative novel metabolic functions for mouse that are supported by gene annotations, but that do not currently appear in existing mouse metabolic networks. The lipidome of these OMVs bears no relation to the mouse lipidome, so the purpose of this particular composition of lipids remains unclear. We conclude from this analysis that through intimate symbiotic evolution OMVs produced by B. thetaiotaomicron are likely to have been adopted as a conduit for small molecules bound for the mammalian host in vivo. PMID: 29276507 [PubMed]

Development of the necrotizing enterocolitis society registry and biorepository.

Tue, 26/12/2017 - 12:35
Related Articles Development of the necrotizing enterocolitis society registry and biorepository. Semin Pediatr Surg. 2018 Feb;27(1):25-28 Authors: Ralls MW, Gadepalli SK, Sylvester KG, Good M Abstract Necrotizing enterocolitis (NEC) is a devastating disease affecting premature infants. New advances in diagnostic and treatment options are desperately needed. Accordingly, the NEC Society initiated a research collaborative with a group of investigators dedicated to advancing the state of NEC-associated knowledge. Recent advances in high-content molecular interrogation and bio-computation (e.g., genomics, transcriptomics, proteomics, and metabolomics) can provide new insights from afflicted infants with NEC, however, individual centers do not have sufficient cases to conduct these studies independently. The development of a NEC Society Biorepository (NSB) has emerged to advance collaboration among institutions through the shared use of biologic samples in the dedicated pursuit of molecular indicators of disease and to gain greater pathophysiologic insights through research. The NSB will provide key infrastructure across several centers to harness the potential for new discoveries, while ensuring specimens are processed consistently, appropriate clinical data is collected, and privacy is maintained. The NSB will provide a comprehensive framework for sharing biological samples and clinical data through a robust and secure system that supports the investigation of research studies on NEC. PMID: 29275812 [PubMed - in process]

Immunogenic and Non-immunogenic Cell Death in the Tumor Microenvironment.

Mon, 25/12/2017 - 12:20
Immunogenic and Non-immunogenic Cell Death in the Tumor Microenvironment. Adv Exp Med Biol. 2017;1036:65-79 Authors: Pitt JM, Kroemer G, Zitvogel L Abstract The host immune system is continuously exposed to dying cells and has evolved to distinguish between cell death events signaling potential threats and physiological apoptosis that should be tolerated. Tumors can use this distinction to their advantage, promoting apoptotic death of cancer cells to induce tolerance and evasion of immunosurveillance. On the other hand, stimuli that cause immunogenic death of cancer cells can induce an effective anti-tumor immune response. In this chapter we discuss different forms of cell death in the tumor microenvironment, and how these interact with host immune cells to impact tumor progression and cancer therapy. We focus on how cancer cells hijack aspects of cell death to promote tumor survival, and how anti-cancer treatments that activate immunogenic death modalities give strong and durable clinical efficacy. PMID: 29275465 [PubMed - in process]

Antitumor Benefits of Antiviral Immunity: An Underappreciated Aspect of Oncolytic Virotherapies.

Mon, 25/12/2017 - 12:20
Antitumor Benefits of Antiviral Immunity: An Underappreciated Aspect of Oncolytic Virotherapies. Trends Immunol. 2017 Dec 20;: Authors: Gujar S, Pol JG, Kim Y, Lee PW, Kroemer G Abstract Oncolytic viruses (OVs) represent a new class of cancer immunotherapeutics. Administration of OVs to cancer-bearing hosts induces two distinct immunities: antiviral and antitumor. While antitumor immunity is beneficial, antiviral immune responses are often considered detrimental for the efficacy of OV-based therapy. The existing dogma postulates that anti-OV immune responses restrict viral replication and spread, and thus reduce direct OV-mediated killing of cancer cells. Accordingly, a myriad of therapeutic strategies aimed at mitigating anti-OV immune responses is presently being tested. Here, we advocate that OV-induced antiviral immune responses hold intrinsic anticancer benefits and are essential for establishing clinically desired antitumor immunity. Thus, to achieve the optimal efficacy of OV-based cancer immunotherapies, strategic management of anti-OV immune responses is of critical importance. PMID: 29275092 [PubMed - as supplied by publisher]

Gas chromatography-mass spectrometry metabolomic study of lipopolysaccharides toxicity on rat basophilic leukemia cells.

Mon, 25/12/2017 - 12:20
Gas chromatography-mass spectrometry metabolomic study of lipopolysaccharides toxicity on rat basophilic leukemia cells. Chem Biol Interact. 2017 Dec 21;: Authors: Cui F, Zhu P, Ji J, Blaženović I, Gholami M, Zhang Y, Sun X Abstract Lipopolysaccharide (LPS) can lead to uncontrollable cytokine production, fatal sepsis syndrome and depression/multiple organ failure, as pathophysiologic demonstration. Various toxic effects of LPS have been extensively reported, mainly on the toxicity of LPS in cellular level, macrophages or tumor cells, etc. This work aimed on the impact of LPS on mast cell metabolism, which focused on LPS-induced cellular metabolic profiles. Gas chromatography-mass spectrometry (GC-MS) based metabolomics strategy was implemented for the endo-metabolites detection in rat basophilic leukemia (RBL-2H3) cells, treated with 10 μg/mL LPS for 24 h, along with multiple time-dose tests of cells viability/apoptosis. Significantly changes metabolites were mainly involved the metabolism of glycine, serine, threonine and the biosynthesis of phenylalanine, tyrosine, tryptophan and pentose phosphate pathway. The endo-metabolism results illustrated that LPS treatment led to downregulation of glycine, serine and threonine metabolism besides pentose phosphate pathway in RBL-2H3 cells. This novel insight into LPS cellular metabolism, provides some heuristic guidance for elucidating the underlying mechanism of LPS-mediated disease. PMID: 29275087 [PubMed - as supplied by publisher]

Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders.

Mon, 25/12/2017 - 12:20
Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders. Anaerobe. 2017 Dec 21;: Authors: Kang DW, Ilhan ZE, Isern NG, Hoyt DW, Howsmon DP, Shaffer M, Lozupone CA, Hahn J, Adams JB, Krajmalnik-Brown R Abstract Evidence supporting that gut problems are linked to ASD symptoms has been accumulating both in humans and animal models of ASD. Gut microbes and their metabolites may be linked not only to GI problems but also to ASD behavior symptoms. Despite this high interest, most previous studies have looked mainly at microbial structure, and studies on fecal metabolites are rare in the context of ASD. Thus, we aimed to detect fecal metabolites that may be present at significantly different concentrations between 21 children with ASD and 23 neurotypical children and to investigate its possible link to human gut microbiome. Using NMR spectroscopy and 16S rRNA gene amplicon sequencing, we examined metabolite profiles and microbial compositions in fecal samples, respectively. Of the 59 metabolites detected, isopropanol concentrations were significantly higher in feces of children with ASD after multiple testing corrections. We also observed similar trends of fecal metabolites to previous studies; children with ASD have higher fecal p-cresol and possibly lower GABA concentrations. In addition, Fisher Discriminant Analysis (FDA) with leave-out-validation suggested that a group of metabolites-caprate, nicotinate, glutamine, thymine, and aspartate-may potentially function as a modest biomarker to separate ASD participants from the neurotypical group (78% sensitivity and 81% specificity). Consistent with our previous Arizona cohort study, we also confirmed lower gut microbial diversity and reduced relative abundances of Prevotella copri in children with ASD. After multiple testing corrections, we also learned that relative abundances of Feacalibacterium prausnitzii and Haemophilus parainfluenzae were lower in feces of children with ASD. Despite a relatively short list of fecal metabolites, the data in this study support that children with ASD have altered metabolite profiles in feces when compared with neurotypical children and warrant further investigation of metabolites in larger cohorts. PMID: 29274915 [PubMed - as supplied by publisher]

A phylogenomic analysis of lichen-feeding tiger moths uncovers evolutionary origins of host chemical sequestration.

Sun, 24/12/2017 - 14:43
Related Articles A phylogenomic analysis of lichen-feeding tiger moths uncovers evolutionary origins of host chemical sequestration. Mol Phylogenet Evol. 2017 Dec 20;: Authors: Scott Chialvo CH, Chialvo P, Holland JD, Anderson TJ, Breinholt JW, Kawahara AY, Zhou X, Liu S, Zaspel JM Abstract Host species utilize a variety of defenses to deter feeding, including secondary chemicals. Some phytophagous insects have evolved tolerance to these chemical defenses, and can sequester secondary defense compounds for use against their own predators and parasitoids. While numerous studies have examined plant-insect interactions, little is known about lichen-insect interactions. Our study focused on reconstructing the evolution of lichen phenolic sequestration in the tiger moth tribe Lithosiini (Lepidoptera: Erebidae: Arctiinae), the most diverse lineage of lichen-feeding moths, with 3,000 described species. We built an RNA-Seq dataset and examined the adult metabolome for the presence of phenolics. Using the transcriptomic dataset, we recover a well-resolved phylogeny of the Lithosiini, and determine that the metabolomes within species are more similar than those among species. Results from an initial ancestral state reconstruction suggest that the ability to sequester phenolics produced by a single chemical pathway preceded generalist sequestration of phenolics produced by multiple chemical pathways. We conclude that phenolics are consistently and selectively sequestered within Lithosiini. Furthermore, sequestration of compounds from a single chemical pathway may represent a synapomorphy of the tribe, and the ability to sequester phenolics produced by multiple pathways arose later. These findings expand on our understanding of the interactions between Lepidoptera and their lichen hosts. PMID: 29274497 [PubMed - as supplied by publisher]

Advanced LC-MS-based methods to study the co-occurrence and metabolization of multiple mycotoxins in cereals and cereal-based food.

Sun, 24/12/2017 - 14:43
Related Articles Advanced LC-MS-based methods to study the co-occurrence and metabolization of multiple mycotoxins in cereals and cereal-based food. Anal Bioanal Chem. 2017 Dec 22;: Authors: Malachová A, Stránská M, Václavíková M, Elliott CT, Black C, Meneely J, Hajšlová J, Ezekiel CN, Schuhmacher R, Krska R Abstract Liquid chromatography (LC) coupled with mass spectrometry (MS) is widely used for the determination of mycotoxins in cereals and cereal-based products. In addition to the regulated mycotoxins, for which official control is required, LC-MS is often used for the screening of a large range of mycotoxins and/or for the identification and characterization of novel metabolites. This review provides insight into the LC-MS methods used for the determination of co-occurring mycotoxins with special emphasis on multiple-analyte applications. The first part of the review is focused on targeted LC-MS approaches using cleanup methods such as solid-phase extraction and immunoaffinity chromatography, as well as on methods based on minimum cleanup (quick, easy, cheap, effective, rugged, and safe; QuEChERS) and dilute and shoot. The second part of the review deals with the untargeted determination of mycotoxins by LC coupled with high-resolution MS, which includes also metabolomics techniques to study the fate of mycotoxins in plants. PMID: 29273904 [PubMed - as supplied by publisher]

[Molecular characterisation defines several subtypes of pancreatic ductal adenocarcinoma].

Sun, 24/12/2017 - 14:43
Related Articles [Molecular characterisation defines several subtypes of pancreatic ductal adenocarcinoma]. Bull Cancer. 2017 Dec 19;: Authors: Raffenne J, Cros J Abstract Multi-omics high throughput analyses lead to the description of multiple molecular subtypes of pancreatic adenocarcinoma with major prognostic impact for most of them. There is no consensual multilevel integrative classification yet like in colon or breast cancers. Genomic classifications have identified a tumor subtype (15% of the patients) with deficient homologous DNA repair-system leading to increase sensitivity to platinum-based therapies and possibly to PARP inhibitors and immunotherapies. Transcriptomic classifications are still debated but all have identified an aggressive subtype with a very poor prognosis, presumably unfit for a surgical approach. Finally, approaches based on metabolomic or proteomic profiling have identified subtypes with a particular sensitivity to compounds targeting the hallmarks metabolomics or oncogenic pathways of each subtype. These classifications were mostly based on tumor cell but the micro-environment is also very heterogeneous and several types of stroma will be described soon. Subtype determination in daily practice remains a major challenge as most technologies used to build these classifications are very expensive, requires dedicated bio-informatics analysis pipelines and are not adapted to routine samples that are mostly formal in fixed paraffin embedded biopsies, in which tumor cells are highly contaminated by the cell from the microenvironment and the clot. PMID: 29273547 [PubMed - as supplied by publisher]

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