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: 2 min 52 sec ago

metabolomics; +25 new citations

Tue, 22/01/2019 - 16:35
25 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/01/22PubMed 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.

Metabolome responses of the sea cucumber Apostichopus japonicus to multiple environmental stresses: Heat and hypoxia.

Mon, 21/01/2019 - 13:08
Related Articles Metabolome responses of the sea cucumber Apostichopus japonicus to multiple environmental stresses: Heat and hypoxia. Mar Pollut Bull. 2019 Jan;138:407-420 Authors: Huo D, Sun L, Zhang L, Ru X, Liu S, Yang H Abstract Economically important marine organisms face severe environmental challenges, such as high temperature and low dissolved oxygen, from global climate change. Adverse environmental factors impact the survival and growth of economically important marine organisms, thereby negatively influencing the aquaculture industry. However, little is known about the responses of sea cucumbers to combined environmental co-stressors till now. In this study, ultra-performance liquid chromatography (UPLC) was utilized to obtain metabolic profiles of sea cucumbers. Changes in the concentrations of 84, 68, and 417 metabolites related to the responses of sea cucumbers to heat (26 °C), hypoxia (2 mg/L) and the combined stress, respectively, were observed and analyzed. Representative biomarkers were discussed in detail, including deltaline, fusarin C, halichondrin B and rapanone. The concentration of metabolites involved in the regulation of energy metabolism, including amino acid, carbohydrate and lipid metabolism were significantly changed, and the tricarboxylic acid (TCA)-cycle was significantly altered under heat plus hypoxia. We interpreted these changes partly as an adaptation mechanism in response to environmental stress. Based on the decreased accumulation of glutamine, we hypothesized that heat stress is the main factor that interferes with the process of glutamic acid-glutamine metabolism. The present study showed that combined environmental stressors have a more extensive impact on the metabolites of the respiratory tree in sea cucumbers than single stress. These results would facilitate further development of the sea cucumber as an echinoderm model to study mechanisms of response to adverse environments, as well as to help advance knowledge of the adaptation of marine organisms to global climate change. PMID: 30660290 [PubMed - in process]

Sanitary pads and diapers contain higher phthalate contents than those in common commercial plastic products.

Sun, 20/01/2019 - 12:48
Sanitary pads and diapers contain higher phthalate contents than those in common commercial plastic products. Reprod Toxicol. 2019 Jan 16;: Authors: Jin Park C, Barakat R, Ulanov A, Li Z, Lin PC, Chiu K, Zhou S, Perez P, Lee J, Flaws J, Ko CJ Abstract Sanitary pads and diapers are made of synthetic plastic materials that can potentially be released while being used. This study measured the amounts of volatile organic compounds (VOCs) (methylene chloride, toluene, and xylene) and phthalates (DBP, DEHP, DEP, and BBP) contained in sanitary pads and diapers. In sanitary pads, 5,900- and 130-fold differences of VOC and phthalate concentrations were seen among the brands. In the diapers, 3- and 63-fold differences of VOC and phthalate concentrations were detected among the brands. VOC concentrations from the sanitary pads and diapers were similar to that of the residential air. However, phthalate concentrations of sanitary pads and diapers were significantly higher than those found in common commercial plastic products. As sanitary pads and diapers are in direct contact with external genitalia for an extended period, there is a probability that a considerable amount of VOCs or phthalates could be absorbed into the reproductive system. PMID: 30659930 [PubMed - as supplied by publisher]

A metabolomic investigation into the temperature-dependent virulence of Pseudomonas plecoglossicida from large yellow croaker (Pseudosciaena crocea).

Sun, 20/01/2019 - 12:48
A metabolomic investigation into the temperature-dependent virulence of Pseudomonas plecoglossicida from large yellow croaker (Pseudosciaena crocea). J Fish Dis. 2019 Jan 18;: Authors: Huang L, Zuo Y, Jiang Q, Su Y, Qin Y, Xu X, Zhao L, Yan Q Abstract Pseudomonas plecoglossicida is associated with multiple fish diseases, and temperature is one of the most important environmental factors related to its outbreak. To elucidate the influence of temperature variation on the pathogen, the global metabolomics of P. plecoglossicida (NZBD9) were analysed at the virulent (18°C) and avirulent (12°C and 28°C) temperatures. The result showed that the levels of Phosphoric acid, Tyrosine, Spermidine and Sucrose were significantly reduced,while Itaconic acid, Glucaric acid and Isomaltose were increased in P. plecoglossicida at 18°C. These metabolic adjustments assist P. plecoglossicida to survive in adverse environments, proliferate in the host, colonize and resist host immune clearance during the initial steps of infection. The results suggested that L321_03626 and L321_18122 genes played a key role in the regulation of these metabolic adaptions and thus regulated P. plecoglossicida virulence at virulent temperature, which was proved by further gene silencing and artificial infection. The present study, for the first time, determines the P. plecoglossicida metabolomic responses to temperature variation, which is helpful to explore its pathogenic mechanism and provides reference for disease control. PMID: 30659613 [PubMed - as supplied by publisher]

Dissecting Heterosis During the Ear Inflorescence Development Stage in Maize via a Metabolomics-based Analysis.

Sun, 20/01/2019 - 12:48
Related Articles Dissecting Heterosis During the Ear Inflorescence Development Stage in Maize via a Metabolomics-based Analysis. Sci Rep. 2019 Jan 18;9(1):212 Authors: Shi X, Zhang X, Shi D, Zhang X, Li W, Tang J Abstract Heterosis can increase the yield of many crops and has been extensively applied in agriculture. In maize, female inflorescence architecture directly determines grain yield. Thus, exploring the relationship between early maize ear inflorescence development and heterosis regarding yield-related traits may be helpful for characterizing the molecular mechanisms underlying heterotic performance. In this study, we fine mapped the overdominant heterotic locus (hlEW2b), associated with ear width, in an approximately 1.98-Mb region based on analyses of chromosome segment substitution lines and the corresponding testcross population. Maize ear inflorescences at the floral meristem stage were collected from two inbred lines, one chromosome segment substitution line that carried hlEW2b (sub-CSSL16), the receptor parent lx9801, and the Zheng58 × sub-CSSL16 and Zheng58 × lx9801 hybrid lines. A total of 256 metabolites were identified, including 31 and 24 metabolites that were differentially accumulated between the two hybrid lines and between the two inbred lines, respectively. Most of these metabolites are involved in complex regulatory mechanisms important for maize ear development. For example, nucleotides are basic metabolites affecting cell composition and carbohydrate synthesis. Additionally, nicotinate and nicotinamide metabolism is important for photosynthesis, plant stress responses, and cell expansion. Moreover, flavonoid and phenolic metabolites regulate auxin transport and cell apoptosis. Meanwhile, phytohormone biosynthesis and distribution influence the cell cycle and cell proliferation. Our results revealed that changes in metabolite contents may affect the heterotic performance related to ear width and yield in maize hybrid lines. This study provides new clues in heterosis at the metabolomics level and implies that differentially accumulated metabolites made distinct contributions to the heterosis at an early stage of ear inflorescences development. PMID: 30659214 [PubMed - in process]

Analytical Methods for Detection of Plant Metabolomes Changes in Response to Biotic and Abiotic Stresses.

Sun, 20/01/2019 - 12:48
Related Articles Analytical Methods for Detection of Plant Metabolomes Changes in Response to Biotic and Abiotic Stresses. Int J Mol Sci. 2019 Jan 17;20(2): Authors: Piasecka A, Kachlicki P, Stobiecki M Abstract Abiotic and biotic stresses are the main reasons of substantial crop yield losses worldwide. Research devoted to reveal mechanisms of plant reactions during their interactions with the environment are conducted on the level of genome, transcriptome, proteome, and metabolome. Data obtained during these studies would permit to define biochemical and physiological mechanisms of plant resistance or susceptibility to affecting factors/stresses. Metabolomics based on mass spectrometric techniques is an important part of research conducted in the direction of breeding new varieties of crop plants tolerant to the affecting stresses and possessing good agronomical features. Studies of this kind are carried out on model, crop and resurrection plants. Metabolites profiling yields large sets of data and due to this fact numerous advanced statistical and bioinformatic methods permitting to obtain qualitative and quantitative evaluation of the results have been developed. Moreover, advanced integration of metabolomics data with these obtained on other omics levels: genome, transcriptome and proteome should be carried out. Such a holistic approach would bring us closer to understanding biochemical and physiological processes of the cell and whole plant interacting with the environment and further apply these observations in successful breeding of stress tolerant or resistant crop plants. PMID: 30658398 [PubMed - in process]

Isolation of anticancer and anti-trypanosome secondary metabolites from the endophytic fungus Aspergillus flocculus via bioactivity guided isolation and MS based metabolomics.

Sat, 19/01/2019 - 12:26
Isolation of anticancer and anti-trypanosome secondary metabolites from the endophytic fungus Aspergillus flocculus via bioactivity guided isolation and MS based metabolomics. J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Jan 06;1106-1107:71-83 Authors: Tawfike AF, Romli M, Clements C, Abbott G, Young L, Schumacher M, Diederich M, Farag M, Edrada-Ebel R Abstract This study aims to identify bioactive anticancer and anti-trypanosome secondary metabolites from the fermentation culture of Aspergillus flocculus endophyte assisted by modern metabolomics technologies. The endophyte was isolated from the stem of the medicinal plant Markhamia platycalyx and identified using phylogenetics. Principle component analysis was employed to screen for the optimum growth endophyte culturing conditions and revealing that the 30-days rice culture (RC-30d) provided the highest levels of the bioactive agents. To pinpoint for active chemicals in endophyte crude extracts and successive fractions, a new application of molecular interaction network is implemented to correlate the chemical and biological profiles of the anti-trypanosome active fractions to highlight the metabolites mediating for bioactivity prior to purification trials. Multivariate data analysis (MVDA), with the aid of dereplication studies, efficiently annotated the putatively active anticancer molecules. The small-scale RC-30d fungal culture was purified using high-throughput chromatographic techniques to yield compound 1, a novel polyketide molecule though inactive. Whereas, active fractions revealed from the bioactivity guided fractionation of medium scale RC-30d culture were further purified to yield 7 metabolites, 5 of which namely cis-4-hydroxymellein, 5-hydroxymellein, diorcinol, botryoisocoumarin A and mellein, inhibited the growth of chronic myelogenous leukemia cell line K562 at 30 μM. 3-Hydroxymellein and diorcinol exhibited a respective inhibition of 56% and 97% to the sleeping sickness causing parasite Trypanosoma brucei brucei. More interestingly, the anti-trypanosomal activity of A. flocculus extract appeared to be mediated by the synergistic effect of the active steroidal compounds i.e. ergosterol peroxide, ergosterol and campesterol. The isolated structures were elucidated by using 1D, 2D NMR and HR-ESIMS. PMID: 30658264 [PubMed - as supplied by publisher]

C60 Fullerols Enhance Copper Toxicity and Alter the Leaf Metabolite and Protein Profile in Cucumber.

Sat, 19/01/2019 - 12:26
C60 Fullerols Enhance Copper Toxicity and Alter the Leaf Metabolite and Protein Profile in Cucumber. Environ Sci Technol. 2019 Jan 18;: Authors: Zhao L, Zhang H, Wang J, Tian L, Li FF, Liu S, Peralta-Videa JR, Gardea-Torresdey JL, White JC, Huang Y, Keller AA, Ji R Abstract Abiotic and biotic stress induce the production of reactive oxygen species (ROS), which limit crop production. Little is known about ROS reduction through the application of exogenous scavengers. In this study, C60 fullerols, a free radical scavenger, was foliar applied to three-week-old cucumber plants (1 or 2 mg/plant) before exposure to copper ions (5 mg/plant). Results showed that C60 fullerols augmented Cu toxicity by increasing the influx of Cu ions into cells (170% and 511%, respectively, for 1 and 2 mg C60 fullerols/plant). We further use metabolomics and proteomics to investigate the mechanism of plant response to C60 fullerols. Metabolomics revealed that C60 fullerols up-regulated antioxidant metabolites including 3-hydroxyflavone, 1,2,4-benzenetriol, and methyl trans-cinnamate, among others, while down-regulated cell membrane metabolites (linolenic and palmitoleic acid). Proteomics analysis revealed that C60 fullerols up-regulated chloroplast proteins involved in water photolysis (PSII protein), light-harvesting (CAB), ATP production (ATP synthase), pigment fixation (Mg-PPIX), and electron transport (Cyt b6f). Chlorophyll fluorescence measurement showed that C60 fullerols significantly accelerated the electron transport rate in leaves (13.3% and 9.4 %, respectively, for 1 and 2 mg C60 fullerols/plant). The global view of the metabolic pathway network suggests that C60 fullerols accelerated electron transport rate, which induced ROS overproduction in chloroplast thylakoids. Plant activated antioxidant and defense pathways to protect the cell from ROS damaging. The revealed benefit (enhance electron transport) and risk (alter membrane composition) suggest a cautious use of C60 fullerols for agricultural application. PMID: 30657311 [PubMed - as supplied by publisher]

Implementing a new variant load model to investigate the role of mtDNA in oxidative stress and inflammation in a bi-ethnic cohort: the SABPA study.

Sat, 19/01/2019 - 12:26
Implementing a new variant load model to investigate the role of mtDNA in oxidative stress and inflammation in a bi-ethnic cohort: the SABPA study. Mitochondrial DNA A DNA Mapp Seq Anal. 2019 Jan 18;:1-8 Authors: Venter M, Malan L, Elson JL, van der Westhuizen FH Abstract Mitochondrial DNA (mtDNA) variation has been implicated in several common complex and degenerative diseases, including cardiovascular disease. Inflammation is seen as part of many of these conditions. Mitochondria feature in inflammatory pathways and it has been suggested that mtDNA variation or released mtDNA might be important in this phenomenon. To determine if mtDNA is involved in the mechanisms leading up to cardiovascular disease, we investigated the role of these variants in seven indicators of oxidative stress and inflammation. This study was done in participants of the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) cohort, a South African bi-ethnic cohort (N = 363). We applied a variant load hypothesis, which is an alternative approach to, and moves away from the classic haplogroup association approaches, to evaluate the cumulative effect of non-synonymous mtDNA variants on measurements of serum peroxides, nitric oxide metabolites, 8-hydroxy-deoxyguanosine, thiobarbituric acid reactive substances, whole blood reduced glutathione, C-reactive protein, and tumor necrosis factor alpha. We found no significant relationships between non-synonymous mtDNA variants and the seven biochemical parameters investigated here. Non-synonymous mtDNA variants are unlikely to impact on disease in this cohort, to an appreciable or measurable extent. PMID: 30657012 [PubMed - as supplied by publisher]

Lugdunomycin, an angucycline-derived molecule with unprecedented chemical architecture.

Sat, 19/01/2019 - 12:26
Related Articles Lugdunomycin, an angucycline-derived molecule with unprecedented chemical architecture. Angew Chem Int Ed Engl. 2019 Jan 18;: Authors: Wu C, van der Heul HU, Melnik AV, Luebben J, Dorrestein PC, Minnaard AJ, Choi YH, van Wezel GP Abstract The angucyclines form the largest family of polycyclic aromatic polyketides, and have been studied extensively. Here we report the discovery of lugdunomycin, a type II polyketide produced by Streptomyces species QL37, which has an unprecedented carbon skeleton synthesized from the angucycline backbone. Lugdunomycin has unique structural characteristics, including a heptacyclic ring system, a spiroatom, two all-carbon stereocenters, and a benzaza[4,3,3]propellane motif. Considering the structural novelty, we propose that lugdunomycin represents a novel subclass of type II polyketides. Metabolomics combined with MS-based molecular networking of Streptomyces sp. QL37 identified 24 other rearranged and non-rearranged angucyclines, whereby 11 of them are previously undescribed. We also propose a biosynthetic route for the limamycins, in addition to that of lugdunomycin. Our work demonstrates that revisiting well-known compound families and their producer strains still is a promising approach for drug discovery. PMID: 30656821 [PubMed - as supplied by publisher]

Dimethyl fumarate treatment induces lipid metabolism alterations that are linked to immunological changes.

Sat, 19/01/2019 - 12:26
Related Articles Dimethyl fumarate treatment induces lipid metabolism alterations that are linked to immunological changes. Ann Clin Transl Neurol. 2019 Jan;6(1):33-45 Authors: Bhargava P, Fitzgerald KC, Venkata SLV, Smith MD, Kornberg MD, Mowry EM, Haughey NJ, Calabresi PA Abstract Objective: Identify metabolic changes produced by dimethyl fumarate (DMF) treatment and link them to immunological effects. Methods: We enrolled 18 MS patients and obtained blood prior to DMF and 6 months postinitiation. We also enrolled 18 healthy controls for comparison. We performed global metabolomics on plasma and used weighted correlation network analysis (WGCNA) to identify modules of correlated metabolites. We identified modules that changed with treatment, followed by targeted metabolomics to corroborate changes identified in global analyses. We correlated changes in metabolite modules and individual metabolites with changes in immunological parameters. Results: We identified alterations in lipid metabolism after DMF treatment - increases in two modules (phospholipids, lysophospholipids and plasmalogens) and reduction in one module (saturated and poly-unsaturated fatty acids) eigen-metabolite values (all P < 0.05). Change in the fatty acid module was greater in participants who developed lymphopenia and was strongly associated with both reduction in absolute lymphocyte counts (r = 0.65; P = 0.005) and change in CD8+ T cell subsets. We also noted significant correlation of change in lymphocyte counts with multiple fatty acid levels (measured by targeted or untargeted methods). Interpretation: This study demonstrates that DMF treatment alters lipid metabolism and that changes in fatty acid levels are related to DMF-induced immunological changes. PMID: 30656182 [PubMed]

Serum level of octanoic acid predicts the efficacy of chemotherapy for colorectal cancer.

Sat, 19/01/2019 - 12:26
Related Articles Serum level of octanoic acid predicts the efficacy of chemotherapy for colorectal cancer. Oncol Lett. 2019 Jan;17(1):831-842 Authors: Iemoto T, Nishiumi S, Kobayashi T, Fujigaki S, Hamaguchi T, Kato K, Shoji H, Matsumura Y, Honda K, Yoshida M Abstract The survival times of patients with advanced colorectal cancer (CRC) have increased due to the introduction of chemotherapy involving irinotecan and cetuximab. However, further studies are required on the effective pretreatment methods for identifying patients with CRC who would respond to particular treatments. The aim of the present study was to identify biomarkers for predicting the efficacy of chemotherapy for CRC. A total of 123 serum samples were collected from 31 patients with CRC just prior to each of the first four rounds of chemotherapy. Serum metabolome analysis was performed using a multiplatform metabolomics system, and univariate Cox regression hazards analysis of the time to disease progression was conducted. Octanoic acid and 1,5-anhydro-D-glucitol were identified as biomarker candidates. In addition, the serum level of octanoic acid was indicated to be significantly associated with the time to disease progression (hazard ratio, 3.3; 95% confidence interval, 1.099-11.840; P=0.033). The serum levels of fatty acids, in particular polyunsaturated fatty acids, tended to be downregulated in the partial response group. The findings of the present study suggest that the serum level of octanoic acid may serve as a useful predictor for the prognosis of CRC. PMID: 30655836 [PubMed]

The Microbiome and Genitourinary Cancer: A Collaborative Review.

Sat, 19/01/2019 - 12:26
Related Articles The Microbiome and Genitourinary Cancer: A Collaborative Review. Eur Urol. 2019 Jan 14;: Authors: Markowski MC, Boorjian SA, Burton JP, Hahn NM, Ingersoll MA, Vareki SM, Pal SK, Sfanos KS Abstract CONTEXT: The recent discovery of the existence of a human genitourinary microbiome has led to the investigation of its role in mediating the pathogenesis of genitourinary malignancies, including bladder, kidney, and prostate cancers. Furthermore, although it is largely recognized that members of the gastrointestinal microbiota are actively involved in drug metabolism, new studies demonstrate additional roles and the potential necessity of the gastrointestinal microbiota in dictating cancer treatment response. OBJECTIVE: To summarize the current evidence of a mechanistic role for the genitourinary and gastrointestinal microbiome in genitourinary cancer initiation and treatment response. EVIDENCE ACQUISITION: We conducted a literature search up to October 2018. Search terms included microbiome, microbiota, urinary microbiome, bladder cancer, urothelial carcinoma, renal cell carcinoma, kidney cancer, testicular cancer, and prostate cancer. EVIDENCE SYNTHESIS: There is preliminary evidence to implicate the members of the genitourinary microbiota as causative factors or cofactors in genitourinary malignancy. Likewise, the current evidence for gastrointestinal microbes in dictating cancer treatment response is mainly correlative; however, we provide examples where therapeutic agents used for the treatment of genitourinary cancers are affected by the human-associated microbiota, or vice versa. Clinical trials, such as fecal microbiota transplant to increase the efficacy of immunotherapy, are currently underway. CONCLUSIONS: The role of the microbiome in genitourinary cancer is an emerging field that merits further studies. Translating microbiome research into clinical action will require incorporation of microbiome surveillance into ongoing and future clinical trials as well as expansion of studies to include metagenomic sequencing and metabolomics. PATIENT SUMMARY: This review covers recent evidence that microbial populations that reside in the genitourinary tract-and were previously not known to exist-may influence the development of genitourinary malignancies including bladder, kidney, and prostate cancers. Furthermore, microbial populations that exist at sites outside of the genitourinary tract, such as those that reside in our gut, may influence cancer development and/or treatment response. PMID: 30655087 [PubMed - as supplied by publisher]

From Omics Technologies to Personalized Transfusion Medicine.

Sat, 19/01/2019 - 12:26
Related Articles From Omics Technologies to Personalized Transfusion Medicine. Expert Rev Proteomics. 2019 Jan 18;: Authors: D'Alessandro A Abstract INTRODUCTION: Blood transfusion is the single most frequent in-hospital medical procedure, a life-saving intervention for millions of recipients worldwide every year. Storage in the blood bank is an enabling strategy for this critical procedure, as it logistically solves the issue of making ~110 million units available for transfusion every year. Unfortunately, storage in the blood bank promotes a series of biochemical and morphological changes to the red blood cell that compromise the integrity and functionality of the erythrocyte in vitro and in animal models, and could negatively impact transfusion outcomes in the recipient. Areas covered: While commenting on the clinical relevance of the storage lesion is beyond the scope of this manuscript, here we will review recent advancements in our understanding of the storage lesion as gleaned through omics technologies. We will focus on how the omics-scale appreciation of the biological variability at the donor and recipient level is impacting our understanding of red blood cell storage biology. Expert commentary: Omics technologies are paving the way for personalized transfusion medicine, a discipline that promises to revolutionize a critical field in medical practice. The era of recipient-tailored additives, processing and storage strategies may not be too far distant in the future. PMID: 30654673 [PubMed - as supplied by publisher]

Combined Proteomic and Metabolomic Profiling of the Arabidopsis thaliana vps29 Mutant Reveals Pleiotropic Functions of the Retromer in Seed Development.

Sat, 19/01/2019 - 12:26
Related Articles Combined Proteomic and Metabolomic Profiling of the Arabidopsis thaliana vps29 Mutant Reveals Pleiotropic Functions of the Retromer in Seed Development. Int J Mol Sci. 2019 Jan 16;20(2): Authors: Durand TC, Cueff G, Godin B, Valot B, Clément G, Gaude T, Rajjou L Abstract The retromer is a multiprotein complex conserved from yeast to humans, which is involved in intracellular protein trafficking and protein recycling. Selection of cargo proteins transported by the retromer depends on the core retromer subunit composed of the three vacuolar protein sorting (VPS) proteins, namely VPS26, VPS29, and VPS35. To gain a better knowledge of the importance of the plant retromer in protein sorting, we carried out a comparative proteomic and metabolomic analysis of Arabidopsis thaliana seeds from the wild-type and the null-retromer mutant vps29. Here, we report that the retromer mutant displays major alterations in the maturation of seed storage proteins and synthesis of lipid reserves, which are accompanied by severely impaired seed vigor and longevity. We also show that the lack of retromer components is counterbalanced by an increase in proteins involved in intracellular trafficking, notably members of the Ras-related proteins in brain (RAB) family proteins. Our study suggests that loss of the retromer stimulates energy metabolism, affects many metabolic pathways, including that of cell wall biogenesis, and triggers an osmotic stress response, underlining the importance of retromer function in seed biology. PMID: 30654520 [PubMed - in process]

1D "Spikelet" Projections from Heteronuclear 2D NMR Data-Permitting 1D Chemometrics While Preserving 2D Dispersion.

Sat, 19/01/2019 - 12:26
Related Articles 1D "Spikelet" Projections from Heteronuclear 2D NMR Data-Permitting 1D Chemometrics While Preserving 2D Dispersion. Metabolites. 2019 Jan 16;9(1): Authors: Tabatabaei Anaraki M, Bermel W, Dutta Majumdar R, Soong R, Simpson M, Monnette M, Simpson AJ Abstract Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for the non-targeted metabolomics of intact biofluids and even living organisms. However, spectral overlap can limit the information that can be obtained from 1D 1H NMR. For example, magnetic susceptibility broadening in living organisms prevents any metabolic information being extracted from solution-state 1D 1H NMR. Conversely, the additional spectral dispersion afforded by 2D 1H-13C NMR allows a wide range of metabolites to be assigned in-vivo in 13C enriched organisms, as well as a greater depth of information for biofluids in general. As such, 2D 1H-13C NMR is becoming more and more popular for routine metabolic screening of very complex samples. Despite this, there are only a very limited number of statistical software packages that can handle 2D NMR datasets for chemometric analysis. In comparison, a wide range of commercial and free tools are available for analysis of 1D NMR datasets. Overtime, it is likely more software solutions will evolve that can handle 2D NMR directly. In the meantime, this application note offers a simple alternative solution that converts 2D 1H-13C Heteronuclear Single Quantum Correlation (HSQC) data into a 1D "spikelet" format that preserves not only the 2D spectral information, but also the 2D dispersion. The approach allows 2D NMR data to be converted into a standard 1D Bruker format that can be read by software packages that can only handle 1D NMR data. This application note uses data from Daphnia magna (water fleas) in-vivo to demonstrate how to generate and interpret the converted 1D spikelet data from 2D datasets, including the code to perform the conversion on Bruker spectrometers. PMID: 30654443 [PubMed]

Layer-by-layer electrochemical biosensors configuring xanthine oxidase and carbon nanotubes/graphene complexes for hypoxanthine and uric acid in human serum solutions.

Sat, 19/01/2019 - 12:26
Related Articles Layer-by-layer electrochemical biosensors configuring xanthine oxidase and carbon nanotubes/graphene complexes for hypoxanthine and uric acid in human serum solutions. Biosens Bioelectron. 2018 Dec 15;121:265-271 Authors: Si Y, Park JW, Jung S, Hwang GS, Goh E, Lee HJ Abstract A selective biosensing platform for the determination of hypoxanthine (Hx) and uric acid (UA) concentrations in both buffer and human serum sample solutions was developed. The biosensor features the layer-by-layer (LbL) self-assembly of negatively charged xanthine oxidase (XOD) and positively charged poly(diallyldimethyl ammonium chloride) (PDDA) wrapped oxidized multi-walled carbon nanotubes and graphene (CNTs-G) complexes (PDDA-CNTs-G) on screen printed carbon electrode (SPCE) surfaces. Catalytic responses of the XOD modified biosensor with the chosen optimum number of layers for LbL assembly on SPCE towards Hx in buffer solutions were first investigated using both cyclic and square wave voltammetries. The peak current at around 0.08 V (vs. Ag/AgCl) associated with the production of UA increased as a function of the Hx concentration due to the surface selective catalytic reaction of XOD and Hx. A linear dynamic range of 5-50 µM Hx with a detection limit of 4.40 µM was obtained and the sensor was further applied to the analysis of Hx in normal human serum solutions in addition to myocardial infarction (MI) patient serum sample solutions from a local hospital. Since untreated serum solutions contain a certain amount of UA, a XOD free SPCE biosensor consisted of only PDDA-CNTs-G was also employed to evaluate the native concentration of UA in the serum and further assist the determination of Hx concentration when using the developed LbL biosensor. Our sensing results for the real biological fluidic solutions were finally validated by comparing to those using liquid chromatography-mass spectrometry(LC-MS). PMID: 30223102 [PubMed - indexed for MEDLINE]

Effects of Qijian mixture on type 2 diabetes assessed by metabonomics, gut microbiota and network pharmacology.

Sat, 19/01/2019 - 12:26
Related Articles Effects of Qijian mixture on type 2 diabetes assessed by metabonomics, gut microbiota and network pharmacology. Pharmacol Res. 2018 04;130:93-109 Authors: Gao K, Yang R, Zhang J, Wang Z, Jia C, Zhang F, Li S, Wang J, Murtaza G, Xie H, Zhao H, Wang W, Chen J Abstract Qijian mixture, a new traditional Chinese medicine (TCM) formula comprising of Astragalus membranaceus, Ramulus euonymi, Coptis chinensis and Pueraria lobata, was designed to ameliorate the type 2 diabetes (T2D), and its safety and efficacy were evaluated in the research by metabonomics, gut microbiota and system pharmacology. To study the hypoglycemic effect of Qijian mixture, male KKay mice (28-30 g, 8-9 week) and C57/BL6 mice (18-19 g, 8-9 week) were used. Thirty KKay diabetic mice were randomly distributed into 5 groups, abbreviated as Model group (Model), Low Qijian Mixture group (QJM(L)), High Qijian Mixture group (QJM(H)), Chinese Medicine (Gegen Qinlian Decoction) Positive group (GGQL), and Western Medicine (Metformin hydrochloride) Positive group (Metformin). C57/BL6 was considered as the healthy control group (Control). Moreover, a system pharmacology approach was utilized to assess the physiological targets involved in the action of Qijian mixture. There was no adverse drug reaction of Qijian mixture in the acute toxicity study and HE result, and, compared with Model group, Qijian mixture could modulate blood glycemic level safely and effectively. Qijian Mixture was lesser effective than metformin hydrochloride; however, both showed similar hypoglycemic trend. Based on 1H NMR based metabonomics study, the profoundly altered metabolites in Qijian mixture treatment group were identified. Qijian mixture-related 55 proteins and 4 signaling pathways, including galactose metabolism, valine, leucine and isoleucine degradation metabolism, aminoacyl-tRNA biosynthesis metabolism and alanine, aspartate and glutamate metabolism pathways, were explored. The PCoA analysis of gut microbiota revealed that Qijian mixture treatment profoundly enriched bacteroidetes. In addition, the system pharmacology paradigm revealed that Qijian mixture acted through TP53, AKT1 and PPARA proteins. It was concluded that Qijian mixture effectively alleviated T2D, and this effect was linked with the altered features of the metabolite profiles and the gut microbiota. PMID: 29391233 [PubMed - indexed for MEDLINE]

metabolomics; +16 new citations

Fri, 18/01/2019 - 15:16
16 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 2019/01/18PubMed 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.

metabolomics; +16 new citations

Fri, 18/01/2019 - 12:16
16 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 2019/01/18PubMed 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.

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