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

Commentary: Epidemiology-Then and Now.

Sat, 24/10/2015 - 14:23
Related Articles Commentary: Epidemiology-Then and Now. Am J Epidemiol. 2015 Oct 21; Authors: Kuller LH Abstract Twenty-five years ago, on the 75th anniversary of the Johns Hopkins Bloomberg School of Public Health, I noted that epidemiologic research was moving away from the traditional approaches used to investigate "epidemics" and their close relationship with preventive medicine. Twenty-five years later, the role of epidemiology as an important contribution to human population research, preventive medicine, and public health is under substantial pressure because of the emphasis on "big data," phenomenology, and personalized medical therapies. Epidemiology is the study of epidemics. The primary role of epidemiology is to identify the epidemics and parameters of interest of host, agent, and environment and to generate and test hypotheses in search of causal pathways. Almost all diseases have a specific distribution in relation to time, place, and person and specific "causes" with high effect sizes. Epidemiology then uses such information to develop interventions and test (through clinical trials and natural experiments) their efficacy and effectiveness. Epidemiology is dependent on new technologies to evaluate improved measurements of host (genomics), epigenetics, identification of agents (metabolomics, proteomics), new technology to evaluate both physical and social environment, and modern methods of data collection. Epidemiology does poorly in studying anything other than epidemics and collections of numerators and denominators without specific hypotheses even with improved statistical methodologies. PMID: 26493266 [PubMed - as supplied by publisher]

Combining Mass Spectrometric Metabolic Profiling with Genomic Analysis: A Powerful Approach for Discovering Natural Products from Cyanobacteria.

Sat, 24/10/2015 - 14:23
Related Articles Combining Mass Spectrometric Metabolic Profiling with Genomic Analysis: A Powerful Approach for Discovering Natural Products from Cyanobacteria. J Nat Prod. 2015 Jul 24;78(7):1671-82 Authors: Kleigrewe K, Almaliti J, Tian IY, Kinnel RB, Korobeynikov A, Monroe EA, Duggan BM, Di Marzo V, Sherman DH, Dorrestein PC, Gerwick L, Gerwick WH Abstract An innovative approach was developed for the discovery of new natural products by combining mass spectrometric metabolic profiling with genomic analysis and resulted in the discovery of the columbamides, a new class of di- and trichlorinated acyl amides with cannabinomimetic activity. Three species of cultured marine cyanobacteria, Moorea producens 3L, Moorea producens JHB, and Moorea bouillonii PNG, were subjected to genome sequencing and analysis for their recognizable biosynthetic pathways, and this information was then compared with their respective metabolomes as detected by MS profiling. By genome analysis, a presumed regulatory domain was identified upstream of several previously described biosynthetic gene clusters in two of these cyanobacteria, M. producens 3L and M. producens JHB. A similar regulatory domain was identified in the M. bouillonii PNG genome, and a corresponding downstream biosynthetic gene cluster was located and carefully analyzed. Subsequently, MS-based molecular networking identified a series of candidate products, and these were isolated and their structures rigorously established. On the basis of their distinctive acyl amide structure, the most prevalent metabolite was evaluated for cannabinomimetic properties and found to be moderate affinity ligands for CB1. PMID: 26149623 [PubMed - indexed for MEDLINE]

A chemometric-assisted method based on gas chromatography-mass spectrometry for metabolic profiling analysis.

Sat, 24/10/2015 - 14:23
Related Articles A chemometric-assisted method based on gas chromatography-mass spectrometry for metabolic profiling analysis. J Chromatogr A. 2015 Jun 19;1399:65-73 Authors: Yu YJ, Fu HY, Zhang L, Wang XY, Sun PJ, Zhang XB, Xie FW Abstract An automatic and efficient data analysis method for comprehensive metabolic profiling analysis is urgently required. In this study, a new chemometric-assisted method for metabolic profiling analysis (CAMMPA) was developed to discover potentially valuable metabolites automatically and efficiently. The proposed method mainly consists of three stages. First, automatic chromatographic peak detection is performed based on the total ion chromatograms of samples to extract chromatographic peaks that can be accurately quantified. Second, a novel peak-shift alignment technique based on peak detection results is implemented to resolve time-shift problems across samples. Consequently, aligned results, including aligned chromatograms, and peak area tables, among others, can be successfully obtained. Third, statistical analysis using results from unsupervised and supervised classification results, together with ANOVA and partial least square-discriminate analysis, is performed to extract potential metabolites. To demonstrate the proposed technique, a complex GC-MS metabolic profiling dataset was measured to identify potential metabolites in tobacco plants of different growth stages as well as different plant tissues after maturation. Results indicated that the efficiency of the routine metabolic profiling analysis procedure can be significantly improved and potential metabolites can be accurately identified with the aid of CAMMPA. PMID: 25943833 [PubMed - indexed for MEDLINE]

Immunoglobulin G (IgG) Fab glycosylation analysis using a new mass spectrometric high-throughput profiling method reveals pregnancy-associated changes.

Sat, 24/10/2015 - 14:23
Related Articles Immunoglobulin G (IgG) Fab glycosylation analysis using a new mass spectrometric high-throughput profiling method reveals pregnancy-associated changes. Mol Cell Proteomics. 2014 Nov;13(11):3029-39 Authors: Bondt A, Rombouts Y, Selman MH, Hensbergen PJ, Reiding KR, Hazes JM, Dolhain RJ, Wuhrer M Abstract The N-linked glycosylation of the constant fragment (Fc) of immunoglobulin G has been shown to change during pathological and physiological events and to strongly influence antibody inflammatory properties. In contrast, little is known about Fab-linked N-glycosylation, carried by ∼ 20% of IgG. Here we present a high-throughput workflow to analyze Fab and Fc glycosylation of polyclonal IgG purified from 5 μl of serum. We were able to detect and quantify 37 different N-glycans by means of MALDI-TOF-MS analysis in reflectron positive mode using a novel linkage-specific derivatization of sialic acid. This method was applied to 174 samples of a pregnancy cohort to reveal Fab glycosylation features and their change with pregnancy. Data analysis revealed marked differences between Fab and Fc glycosylation, especially in the levels of galactosylation and sialylation, incidence of bisecting GlcNAc, and presence of high mannose structures, which were all higher in the Fab portion than the Fc, whereas Fc showed higher levels of fucosylation. Additionally, we observed several changes during pregnancy and after delivery. Fab N-glycan sialylation was increased and bisection was decreased relative to postpartum time points, and nearly complete galactosylation of Fab glycans was observed throughout. Fc glycosylation changes were similar to results described before, with increased galactosylation and sialylation and decreased bisection during pregnancy. We expect that the parallel analysis of IgG Fab and Fc, as set up in this paper, will be important for unraveling roles of these glycans in (auto)immunity, which may be mediated via recognition by human lectins or modulation of antigen binding. PMID: 25004930 [PubMed - indexed for MEDLINE]

metabolomics; +21 new citations

Fri, 23/10/2015 - 13:17
21 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 2015/10/23PubMed comprises more than 24 million 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.

Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine.

Thu, 22/10/2015 - 14:56
Related Articles Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine. Immunity. 2015 Oct 20;43(4):817-829 Authors: Haghikia A, Jörg S, Duscha A, Berg J, Manzel A, Waschbisch A, Hammer A, Lee DH, May C, Wilck N, Balogh A, Ostermann AI, Schebb NH, Akkad DA, Grohme DA, Kleinewietfeld M, Kempa S, Thöne J, Demir S, Müller DN, Gold R, Linker RA Abstract Growing empirical evidence suggests that nutrition and bacterial metabolites might impact the systemic immune response in the context of disease and autoimmunity. We report that long-chain fatty acids (LCFAs) enhanced differentiation and proliferation of T helper 1 (Th1) and/or Th17 cells and impaired their intestinal sequestration via p38-MAPK pathway. Alternatively, dietary short-chain FAs (SCFAs) expanded gut T regulatory (Treg) cells by suppression of the JNK1 and p38 pathway. We used experimental autoimmune encephalomyelitis (EAE) as a model of T cell-mediated autoimmunity to show that LCFAs consistently decreased SCFAs in the gut and exacerbated disease by expanding pathogenic Th1 and/or Th17 cell populations in the small intestine. Treatment with SCFAs ameliorated EAE and reduced axonal damage via long-lasting imprinting on lamina-propria-derived Treg cells. These data demonstrate a direct dietary impact on intestinal-specific, and subsequently central nervous system-specific, Th cell responses in autoimmunity, and thus might have therapeutic implications for autoimmune diseases such as multiple sclerosis. PMID: 26488817 [PubMed - as supplied by publisher]

Pulsed Direct Current Electrospray: Enabling Systematic Analysis of Small Volume Sample by Boosting Sample Economy.

Thu, 22/10/2015 - 14:56
Related Articles Pulsed Direct Current Electrospray: Enabling Systematic Analysis of Small Volume Sample by Boosting Sample Economy. Anal Chem. 2015 Oct 21; Authors: Wei Z, Xiong X, Guo C, Si X, Zhao Y, He M, Yang C, Xu W, Tang F, Fang X, Zhang S, Zhang X Abstract We had developed pulsed direct current electrospray ionization mass spectrometry (Pulsed-DC-ESI-MS) for systematically profiling and de-termining components in small volume sample. Pulsed-DC-ESI utilized constant high voltage to induce the generation of single polarity pulsed elec-trospray remotely. This method had significantly boosted the sample economy, so as to obtain several minutes MS signal duration from merely picoliter volume sample. The elongated MS signal duration enable us to collect abundant MS2 information of interested components in a small volume sample for systematical analysis. This method had been successfully applied for single cell metabolomics analysis. We had obtained 2-D profile of metabolites (including exact mass and MS2 data) from single plant and mammalian cell, concerning 1034 components and 656 com-ponents for Allium cepa and HeLa cell, respectively. Further identification had found 162 compounds and 28 different modification groups of 141 saccharides in single Allium cepa Cell, indicating Pulsed-DC-ESI a powerful tool for small volume sample systematical analysis. PMID: 26488206 [PubMed - as supplied by publisher]

The application of multi-omics and systems biology to identify therapeutic targets in chronic kidney disease.

Thu, 22/10/2015 - 14:56
Related Articles The application of multi-omics and systems biology to identify therapeutic targets in chronic kidney disease. Nephrol Dial Transplant. 2015 Oct 20; Authors: Cisek K, Krochmal M, Klein J, Mischak H Abstract The quest for the ideal therapeutic target in chronic kidney disease (CKD) has been riddled with many obstacles stemming from the molecular complexity of the disease and its co-morbidities. Recent advances in omics technologies and the resulting amount of available data encompassing genomics, proteomics, peptidomics, transcriptomics and metabolomics has created an opportunity for integrating omics datasets to build a comprehensive and dynamic model of the molecular changes in CKD for the purpose of biomarker and drug discovery. This article reviews relevant concepts in omics data integration using systems biology, a mathematical modelling method that globally describes a biological system on the basis of its modules and the functional connections that govern their behaviour. The review describes key databases and bioinformatics tools, as well as the challenges and limitations of the current state of the art, along with practical application to CKD therapeutic target discovery. Moreover, it describes how systems biology and visualization tools can be used to generate clinically relevant molecular models with the capability to identify specific disease pathways, recognize key events in disease development and track disease progression. PMID: 26487673 [PubMed - as supplied by publisher]

Integrative metabonomics as potential method for diagnosis of thyroid malignancy.

Thu, 22/10/2015 - 14:56
Related Articles Integrative metabonomics as potential method for diagnosis of thyroid malignancy. Sci Rep. 2015;5:14869 Authors: Tian Y, Nie X, Xu S, Li Y, Huang T, Tang H, Wang Y Abstract Thyroid nodules can be classified into benign and malignant tumors. However, distinguishing between these two types of tumors can be challenging in clinics. Since malignant nodules require surgical intervention whereas asymptomatic benign tumors do not, there is an urgent need for new techniques that enable accurate diagnosis of malignant thyroid nodules. Here, we used (1)H NMR spectroscopy coupled with pattern recognition techniques to analyze the metabonomes of thyroid tissues and their extracts from thyroid lesion patients (n = 53) and their adjacent healthy thyroid tissues (n = 46). We also measured fatty acid compositions using GC-FID/MS techniques as complementary information. We demonstrate that thyroid lesion tissues can be clearly distinguishable from healthy tissues, and malignant tumors can also be distinguished from the benign tumors based on the metabolic profiles, both with high sensitivity and specificity. In addition, we show that thyroid lesions are accompanied with disturbances of multiple metabolic pathways, including alterations in energy metabolism (glycolysis, lipid and TCA cycle), promotions in protein turnover, nucleotide biosynthesis as well as phosphatidylcholine biosynthesis. These findings provide essential information on the metabolic features of thyroid lesions and demonstrate that metabonomics technology can be potentially useful in the rapid and accurate preoperative diagnosis of malignant thyroid nodules. PMID: 26486570 [PubMed - in process]

Symphonia globulifera, a widespread source of complex metabolites with potent biological activities.

Thu, 22/10/2015 - 14:56
Related Articles Symphonia globulifera, a widespread source of complex metabolites with potent biological activities. Planta Med. 2015 Jan;81(2):95-107 Authors: Fromentin Y, Cottet K, Kritsanida M, Michel S, Gaboriaud-Kolar N, Lallemand MC Abstract Symphonia globulifera has been widely used in traditional medicine and has therefore been subjected to several phytochemical studies in the American and African continents. Interestingly, some disparities have been observed concerning its metabolic profile. Several phytochemical studies of S. globulifera have led to the identification of more than 40 compounds, including several polycyclic polyprenylated acylphloroglucinols. Biological evaluations have pointed out the promising biological activities of these secondary metabolites, mostly as antiparasitic or antimicrobial, confirming the traditional use of this plant. The purpose of this review is to describe the natural occurrence, botanical aspects, ethnomedicinal use, structure, and biogenesis, as well as biological activities of compounds isolated from this species according to their provenance. PMID: 25590372 [PubMed - indexed for MEDLINE]

The toxicity of acute exposure to T-2 toxin evaluated by the metabonomics technique.

Thu, 22/10/2015 - 14:56
Related Articles The toxicity of acute exposure to T-2 toxin evaluated by the metabonomics technique. Mol Biosyst. 2015 Mar;11(3):882-91 Authors: Wan Q, Wu G, He Q, Tang H, Wang Y Abstract T-2 toxin is a common contaminant in grains and animal feedstuff, which becomes an increasing threat to human and animal health due to its high toxicity. Investigating the systemic effects of T-2 toxin is important to evaluate the toxicity and facilitate the assessment of food safety. In our investigation, rats were treated with a single dose of T-2 toxin at dosage levels of 0, 0.5, 2.0 and 4.0 mg kg(-1) body weight via gavage. The metabolic profiles of body fluids and multiple organs were obtained by NMR spectroscopy and analyzed by multivariate data analysis methods. The results showed that low and moderate doses of T-2 toxin only influenced the urinary metabonomes, while a high dose of T-2 toxin induced metabolic alterations in urine and multiple organs. These changes included alterations in the levels of membrane metabolites, TCA cycle intermediates, a range of amino acids, nucleosides and nucleotides. T-2 toxin exposure impaired spleen function, causing immunotoxicity, and inhibited protein and DNA biosynthesis. In addition, T-2 toxin also caused oxidative stress and disturbance in energy metabolism and gut microbiome. Our work provided a comprehensive insight into T-2 toxicity and revealed the great potential of metabonomics in assessing the impact of a toxic compound. PMID: 25588579 [PubMed - indexed for MEDLINE]

Metabolomic analysis reveals functional overlapping of three signal transduction proteins in regulating ethanol tolerance in cyanobacterium Synechocystis sp. PCC 6803.

Thu, 22/10/2015 - 14:56
Related Articles Metabolomic analysis reveals functional overlapping of three signal transduction proteins in regulating ethanol tolerance in cyanobacterium Synechocystis sp. PCC 6803. Mol Biosyst. 2015 Mar;11(3):770-82 Authors: Zhu Y, Pei G, Niu X, Shi M, Zhang M, Chen L, Zhang W Abstract Low ethanol tolerance is a crucial factor that restricts the feasibility of bioethanol production in renewable cyanobacterial systems. Our previous studies showed that several transcriptional regulators were differentially regulated by exogenous ethanol in Synechocystis. In this study, by constructing knockout mutants of 34 Synechocystis putative transcriptional regulator-encoding genes and analyzing their phenotypes under ethanol stress, we found that three mutants of regulatory gene sll1392, sll1712 and slr1860 grew poorly in the BG11 medium supplemented with ethanol when compared with the wild type in the same medium, suggesting that the genes may be involved in the regulation of ethanol tolerance. To decipher the regulatory mechanism, targeted LC-MS and untargeted GC-MS approaches were employed to determine metabolic profiles of the three mutants and the wild type under both normal and ethanol stress conditions. The results were then subjected to PCA and WGCNA analyses to determine the responsive metabolites and metabolic modules related to ethanol tolerance. Interestingly, the results showed that there was a significant overlapping of the responsive metabolites and metabolic modules between three regulatory proteins, suggesting that a possible crosstalk between various regulatory proteins may be involved in combating against ethanol toxicity in Synechocystis. The study provided new insights into ethanol-tolerance regulation and knowledge important to rational tolerance engineering in Synechocystis. PMID: 25502571 [PubMed - indexed for MEDLINE]

Upregulation of colonic luminal polyamines produced by intestinal microbiota delays senescence in mice.

Thu, 22/10/2015 - 14:56
Related Articles Upregulation of colonic luminal polyamines produced by intestinal microbiota delays senescence in mice. Sci Rep. 2014;4:4548 Authors: Kibe R, Kurihara S, Sakai Y, Suzuki H, Ooga T, Sawaki E, Muramatsu K, Nakamura A, Yamashita A, Kitada Y, Kakeyama M, Benno Y, Matsumoto M Abstract Prevention of quality of life (QOL) deterioration is associated with the inhibition of geriatric diseases and the regulation of brain function. However, no substance is known that prevents the aging of both body and brain. It is known that polyamine concentrations in somatic tissues (including the brain) decrease with increasing age, and polyamine-rich foods enhance longevity in yeast, worms, flies, and mice, and protect flies from age-induced memory impairment. A main source of exogenous polyamines is the intestinal lumen, where they are produced by intestinal bacteria. We found that arginine intake increased the concentration of putrescine in the colon and increased levels of spermidine and spermine in the blood. Mice orally administered with arginine in combination with the probiotic bifidobacteria LKM512 long-term showed suppressed inflammation, improved longevity, and protection from age-induced memory impairment. This study shows that intake of arginine and LKM512 may prevent aging-dependent declines in QOL via the upregulation of polyamines. PMID: 24686447 [PubMed - indexed for MEDLINE]

Preparation of Mitochondrial Enriched Fractions for Metabolic Analysis in Drosophila.

Wed, 21/10/2015 - 14:03
Preparation of Mitochondrial Enriched Fractions for Metabolic Analysis in Drosophila. J Vis Exp. 2015;(103) Authors: Villa-Cuesta E, Rand DM Abstract Since mitochondria play roles in amino acid metabolism, carbohydrate metabolism and fatty acid oxidation, defects in mitochondrial function often compromise the lives of those who suffer from these complex diseases. Detecting mitochondrial metabolic changes is vital to the understanding of mitochondrial disorders and mitochondrial responses to pharmacological agents. Although mitochondrial metabolism is at the core of metabolic regulation, the detection of subtle changes in mitochondrial metabolism may be hindered by the overrepresentation of other cytosolic metabolites obtained using whole organism or whole tissue extractions. Here we describe an isolation method that detected pronounced mitochondrial metabolic changes in Drosophila that were distinct between whole-fly and mitochondrial enriched preparations. To illustrate the sensitivity of this method, we used a set of Drosophila harboring genetically diverse mitochondrial DNAs (mtDNA) and exposed them to the drug rapamycin. Using this method we showed that rapamycin modifies mitochondrial metabolism in a mitochondrial-genotype-dependent manner. However, these changes are much more distinct in metabolomics studies when metabolites were extracted from mitochondrial enriched fractions. In contrast, whole tissue extracts only detected metabolic changes mediated by the drug rapamycin independently of mtDNAs. PMID: 26485391 [PubMed - as supplied by publisher]

Metabolomics: Budgeting on a diet.

Wed, 21/10/2015 - 14:03
Metabolomics: Budgeting on a diet. Nat Chem Biol. 2015 Oct 20;11(11):828 Authors: Miura G PMID: 26485072 [PubMed - as supplied by publisher]

Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats.

Wed, 21/10/2015 - 14:03
Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats. PLoS One. 2015;10(10):e0140884 Authors: Katakura M, Hashimoto M, Inoue T, Mamun AA, Tanabe Y, Arita M, Shido O Abstract Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography-tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney. PMID: 26485038 [PubMed - as supplied by publisher]

The Use of p-Aminobenzoic Acid as a Probe Substance for the Targeted Profiling of Glycine Conjugation.

Wed, 21/10/2015 - 14:03
The Use of p-Aminobenzoic Acid as a Probe Substance for the Targeted Profiling of Glycine Conjugation. J Biochem Mol Toxicol. 2015 Oct 20; Authors: Nortje C, van der Sluis R, van Dijk AA, Erasmus E Abstract Glycine conjugation facilitates the metabolism of toxic aromatic acids, capable of disrupting mitochondrial integrity. Owing to the high exposure to toxic substrates, characterization of individual glycine conjugation capacity, and its regulatory factors has become increasingly important. Aspirin and benzoate have been employed for this purpose; however, adverse reactions, aspirin intolerance, and Reye's syndrome in children are substantial drawbacks. The goal of this study was to investigate p-aminobenzoic acid (PABA) as an alternative glycine conjugation probe. Ten human volunteers participated in a PABA challenge test, and p-aminohippuric acid (PAHA), p-acetamidobenzoic acid, and p-acetamidohippuric acid were quantified in urine. The glycine N-acyltransferase gene of the volunteers was also screened for two polymorphisms associated with normal and increased enzyme activity. All of the individuals were homozygous for increased enzyme activity, but excretion of PAHA varied significantly (16-56%, hippurate ratio). The intricacies of PABA metabolism revealed possible limiting factors and the potential of PABA as an indicator of Phase 0 biotransformation. PMID: 26484797 [PubMed - as supplied by publisher]

Pathogenesis of endothelial cell dysfunction in chronic kidney disease: a retrospective and what the future may hold.

Wed, 21/10/2015 - 14:03
Pathogenesis of endothelial cell dysfunction in chronic kidney disease: a retrospective and what the future may hold. Kidney Res Clin Pract. 2015 Jun;34(2):76-82 Authors: Goligorsky MS Abstract Cardiovascular complications dominate the landscape of chronic kidney diseases (CKD). Endothelial cell dysfunction (ECD) is a well-known culprit of cardiovascular morbidity and it develops in CKD with remarkable frequency. This brief overview of ECD in CKD scans two decades of studies performed in my laboratory, from genetic analyses to proteomic and metabolomics screens. I provide a detailed description of findings related to the premature senescence of endothelial cells, cell transition from the endothelial to mesenchymal phenotype, and stages of development of ECD. Clinical utility of some of these findings is illustrated with data on laser-Doppler flowmetry and imaging in patients with CKD. Some currently available and emerging therapeutic options for the management of ECD are briefly presented. PMID: 26484026 [PubMed]

Improvement in Long-Term Memory following Chronic Administration of Eryngium planum Root Extract in Scopolamine Model: Behavioral and Molecular Study.

Wed, 21/10/2015 - 14:03
Improvement in Long-Term Memory following Chronic Administration of Eryngium planum Root Extract in Scopolamine Model: Behavioral and Molecular Study. Evid Based Complement Alternat Med. 2015;2015:145140 Authors: Ozarowski M, Thiem B, Mikolajczak PL, Piasecka A, Kachlicki P, Szulc M, Kaminska E, Bogacz A, Kujawski R, Bartkowiak-Wieczorek J, Kujawska M, Jodynis-Liebert J, Budzianowski J, Kędziora I, Seremak-Mrozikiewicz A, Czerny B, Bobkiewicz-Kozłowska T Abstract Eryngium planum L. (EP) is as a rare medicinal plant with a lot of potentials as pharmaceutical crops. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 70% ethanol extract of EP roots (200 mg/kg, p.o.) on behavioral and cognitive responses in Wistar rats linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex. On the last day of experiment, 30 min after the last dose of EP or Huperzine A (HU), scopolamine (SC) was given at a dose of 0.5 mg/kg b.w. intraperitoneally. The results of a passive avoidance test showed an improvement in long-term memory produced by the EP extract in both scopolamine-induced rats and control group. EP caused an insignificant inhibition of AChE and BuChE activities in the frontal cortex and the hippocampus. EP decreased mRNA AChE, BuChE, and BACE-1 levels, especially in the cortex. Our results suggest that the EP extract led to the improvement of the long-term memory in rats coupled with total saponin content. The mechanism of EP action is probably complicated, since HPLC-MS analysis showed 64 chemical compounds (phenolics, saponins) in the extract of EP roots. PMID: 26483842 [PubMed]

Metabolomic and high-throughput sequencing analysis-modern approach for the assessment of biodeterioration of materials from historic buildings.

Wed, 21/10/2015 - 14:03
Metabolomic and high-throughput sequencing analysis-modern approach for the assessment of biodeterioration of materials from historic buildings. Front Microbiol. 2015;6:979 Authors: Gutarowska B, Celikkol-Aydin S, Bonifay V, Otlewska A, Aydin E, Oldham AL, Brauer JI, Duncan KE, Adamiak J, Sunner JA, Beech IB Abstract Preservation of cultural heritage is of paramount importance worldwide. Microbial colonization of construction materials, such as wood, brick, mortar, and stone in historic buildings can lead to severe deterioration. The aim of the present study was to give modern insight into the phylogenetic diversity and activated metabolic pathways of microbial communities colonized historic objects located in the former Auschwitz II-Birkenau concentration and extermination camp in Oświecim, Poland. For this purpose we combined molecular, microscopic and chemical methods. Selected specimens were examined using Field Emission Scanning Electron Microscopy (FESEM), metabolomic analysis and high-throughput Illumina sequencing. FESEM imaging revealed the presence of complex microbial communities comprising diatoms, fungi and bacteria, mainly cyanobacteria and actinobacteria, on sample surfaces. Microbial diversity of brick specimens appeared higher than that of the wood and was dominated by algae and cyanobacteria, while wood was mainly colonized by fungi. DNA sequences documented the presence of 15 bacterial phyla representing 99 genera including Halomonas, Halorhodospira, Salinisphaera, Salinibacterium, Rubrobacter, Streptomyces, Arthrobacter and nine fungal classes represented by 113 genera including Cladosporium, Acremonium, Alternaria, Engyodontium, Penicillium, Rhizopus, and Aureobasidium. Most of the identified sequences were characteristic of organisms implicated in deterioration of wood and brick. Metabolomic data indicated the activation of numerous metabolic pathways, including those regulating the production of primary and secondary metabolites, for example, metabolites associated with the production of antibiotics, organic acids and deterioration of organic compounds. The study demonstrated that a combination of electron microscopy imaging with metabolomic and genomic techniques allows to link the phylogenetic information and metabolic profiles of microbial communities and to shed new light on biodeterioration processes. PMID: 26483760 [PubMed]

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