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

metabolomics; +16 new citations

Tue, 18/10/2016 - 13:43
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 2016/10/18PubMed 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.

A metabolomics investigation of the function of the ESX-1 gene cluster in mycobacteria.

Mon, 17/10/2016 - 13:08
A metabolomics investigation of the function of the ESX-1 gene cluster in mycobacteria. Microb Pathog. 2016 Oct 12;: Authors: Loots DT, Swanepoel CC, Newton-Foot M, van Pittius NC Abstract The ESX-1 gene cluster, encoding the Type-VII secretion (T7S) system and its virulence associated proteins, ESAT-6 and CFP-10, is thought to be responsible for the transport of extracellular proteins across the hydrophobic and highly impermeable, cell envelope of Mycobacterium, and is involved in virulence in Mycobacterium tuberculosis, the causative agent of tuberculosis. Using a GCxGC-TOFMS metabolomics approach, a M. smegmatis ESX-1 knock-out strain (ΔESX-1ms) was compared to that of the M. smegmatis wild-type parent strain, and the metabolite markers due to the presence or absence of the ESX-1 gene cluster were identified. A general increase in specific metabolites in the ΔESX-1ms, confirmed the roles previously described for ESX-1 in mycolic acid biosynthesis and cell wall integrity. However, a number of other metabolite markers identified indicates ESX-1 has an additional role the in cell envelope structure, altering the levels of antioxidants and energy metabolism. Furthermore, the metabolome profiles correlated with the metabolomic variation observed when comparing a hyper- and hypo-virulent Beijing strain of M. tuberculosis, suggesting that the pathways which modulate virulence in M. tuberculosis are also influenced by ESX-1, reaffirming the previously described association of ESX-1 with virulence and cell envelope biogenesis. PMID: 27744102 [PubMed - as supplied by publisher]

metabolomics; +19 new citations

Sun, 16/10/2016 - 14:55
19 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 2016/10/16PubMed 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.

metabolomics; +24 new citations

Fri, 14/10/2016 - 12:45
24 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 2016/10/14PubMed 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.

metabolomics; +19 new citations

Thu, 13/10/2016 - 14:53
19 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 2016/10/13PubMed 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.

Pesticides in human milk of Western Australian women and their influence on infant growth outcomes: A cross-sectional study.

Wed, 12/10/2016 - 20:14
Pesticides in human milk of Western Australian women and their influence on infant growth outcomes: A cross-sectional study. Chemosphere. 2016 Oct 8;167:247-254 Authors: Du J, Gridneva Z, Gay MC, Trengove RD, Hartmann PE, Geddes DT Abstract Persistent organic pollutants in human milk (HM) at high levels are considered to be detrimental to the breastfed infant. To determine the pesticide concentration in HM, a pilot cross-sectional study of 40 Western Australian (WA) women was carried out. Gas chromatography-tandem mass spectrometry (GC-MS/MS) with a validated QuEChERS was used for the analysis of 88 pesticides in HM. p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) with a mean concentration of 62.8 ± 54.5 ng/g fat was found, whereas other organochlorines, organophosphates, carbamates and pyrethroids were not detected in HM. Overall, no association was observed between HM p,p'-DDE concentrations and maternal age, parity, body mass index and percentage fat mass. Furthermore, for the first time no significant association was found between p,p'-DDE concentrations in HM and infant growth outcomes such as weight, length, head circumference and percentage fat mass. The calculated daily intake was significantly different to the estimated daily intake of total DDTs and was well below the guideline proposed by WHO. The DDTs levels in WA have also significantly decreased by 42 - fold since the 1970s and are currently the lowest in Australia. PMID: 27728883 [PubMed - as supplied by publisher]

Examination of Endogenous Peptides in Medicago truncatula Using Mass Spectrometry Imaging.

Wed, 12/10/2016 - 20:14
Examination of Endogenous Peptides in Medicago truncatula Using Mass Spectrometry Imaging. J Proteome Res. 2016 Oct 11;: Authors: Gemperline E, Keller C, Jayaraman D, Maeda J, Sussman MR, Ané JM, Li L Abstract Plant science is an important, rapidly developing area of study. Within plant science, one area of study that has grown tremendously with recent technological advances, such as mass spectrometry, is the field of plant-omics; however, plant peptidomics is relatively underdeveloped in comparison with proteomics and metabolomics. Endogenous plant peptides can act as signaling molecules and have been shown to affect cell division, development, nodulation, reproduction, symbiotic associations, and defense reactions. There is a growing need to uncover the role of endogenous peptides on a molecular level. Mass spectrometric imaging (MSI) is a valuable tool for biological analyses as it allows for the detection of thousands of analytes in a single experiment and also displays spatial information for the detected analytes. Despite the prediction of a large number of plant peptides, their detection and imaging with spatial localization and chemical specificity is currently lacking. Here we analyzed the endogenous peptides and proteins in Medicago truncatula using matrix-assisted laser desorption/ionization (MALDI)-MSI. Hundreds of endogenous peptides and protein fragments were imaged, with interesting peptide spatial distribution changes observed between plants in different developmental stages. PMID: 27726374 [PubMed - as supplied by publisher]

Systems analysis of metabolism and the transcriptome in Arabidopsis thaliana roots reveals differential co-regulation upon iron, sulfur and potassium deficiency.

Wed, 12/10/2016 - 20:14
Systems analysis of metabolism and the transcriptome in Arabidopsis thaliana roots reveals differential co-regulation upon iron, sulfur and potassium deficiency. Plant Cell Environ. 2016 Oct 10;: Authors: Forieri I, Sticht C, Reichelt M, Gretz N, Hawkesford MJ, Malagoli M, Wirtz M, Hell R Abstract Deprivation of mineral nutrients causes significant retardation of plant growth. This retardation is associated with nutrient specific and general stress-induced transcriptional responses. In this study we adjusted the external supply of iron, potassium and sulfur to cause the same retardation of shoot growth. Nevertheless, limitation by individual nutrients resulted in specific morphological adaptations and distinct shifts within the root metabolite fingerprint. The metabolic shifts affected key metabolites of primary metabolism and the stress-related phytohormones, jasmonic-, salicylic- and abscisic acid. These phytohormone signatures contributed to specific nutrient deficiency-induced transcriptional regulation. Limitation by the micronutrient iron caused the strongest regulation and affected 18 % of the root transcriptome. Only 130 genes were regulated by all nutrients. Specific co-regulation between the iron and sulfur metabolic routes upon iron or sulfur deficiency was observed. Interestingly, iron deficiency caused regulation of a different set of genes of the sulfur assimilation pathway compared to sulfur deficiency itself, which demonstrates the presence of specific signal-transduction systems for the cross-regulation of the pathways. Combined iron and sulfur starvation experiments demonstrated that a requirement for a specific nutrient can overrule this cross-regulation. The comparative metabolomics and transcriptomics approach used dissected general-stress from nutrient-specific regulation in roots of Arabidopsis. This article is protected by copyright. All rights reserved. PMID: 27726154 [PubMed - as supplied by publisher]

Reduced Triacylglycerol Mobilization during Seed Germination and Early Seedling Growth in Arabidopsis Containing Nutritionally Important Polyunsaturated Fatty Acids.

Wed, 12/10/2016 - 20:14
Reduced Triacylglycerol Mobilization during Seed Germination and Early Seedling Growth in Arabidopsis Containing Nutritionally Important Polyunsaturated Fatty Acids. Front Plant Sci. 2016;7:1402 Authors: Shrestha P, Callahan DL, Singh SP, Petrie JR, Zhou XR Abstract There are now several examples of plant species engineered to synthesize and accumulate nutritionally important polyunsaturated fatty acids in their seed triacylglycerols (TAG). The utilization of TAG in germinating seeds of such transgenic plants was unknown. In this study, we examined the TAG utilization efficiency during seed germination in transgenic Arabidopsis seeds containing several examples of these fatty acids. Seed TAG species with native fatty acids had higher utilization rate than the TAG species containing transgenically produced polyunsaturated fatty acids. Conversely, quantification of the fatty acid components remaining in the total TAG after early stages of seed germination revealed that the undigested TAGs tended to contain elevated levels of the engineered polyunsaturated fatty acids (PUFA). LC-MS analysis further revealed asymmetrical mobilization rates for the individual TAG species. TAGs which contained multiple PUFA fatty acids were mobilized slower than the species containing single PUFA. The mobilized engineered fatty acids were used in de novo membrane lipid synthesis during seedling development. PMID: 27725822 [PubMed - in process]

Transcriptomic and Metabolomic Analysis Revealed Multifaceted Effects of Phage Protein Gp70.1 on Pseudomonas aeruginosa.

Wed, 12/10/2016 - 20:14
Transcriptomic and Metabolomic Analysis Revealed Multifaceted Effects of Phage Protein Gp70.1 on Pseudomonas aeruginosa. Front Microbiol. 2016;7:1519 Authors: Zhao X, Chen C, Jiang X, Shen W, Huang G, Le S, Lu S, Zou L, Ni Q, Li M, Zhao Y, Wang J, Rao X, Hu F, Tan Y Abstract The impact of phage infection on the host cell is severe. In order to take over the cellular machinery, some phage proteins were produced to shut off the host biosynthesis early in the phage infection. The discovery and identification of these phage-derived inhibitors have a significant prospect of application in antibacterial treatment. This work presented a phage protein, gp70.1, with non-specific inhibitory effects on Pseudomonas aeruginosa and Escherichia coli. Gp70.1 was encoded by early gene - orf 70.1 from P. aeruginosa phage PaP3. The P. aeruginosa with a plasmid encoding gp70.1 showed with delayed growth and had the appearance of a small colony. The combination of multifaceted analysis including microarray-based transcriptomic analysis, RT-qPCR, nuclear magnetic resonance (NMR) spectroscopy-based metabolomics and phenotype experiments were performed to investigate the effects of gp70.1 on P. aeruginosa. A total of 178 genes of P. aeruginosa mainly involved in extracellular function and metabolism were differentially expressed in the presence of gp70.1 at three examined time points. Furthermore, our results indicated that gp70.1 had an extensive impact on the extracellular phenotype of P. aeruginosa, such as motility, pyocyanin, extracellular protease, polysaccharide, and cellulase. For the metabolism of P. aeruginosa, the main effect of gp70.1 was the reduction of amino acid consumption. Finally, the RNA polymerase sigma factor RpoS was identified as a potential cellular target of gp70.1. Gp70.1 was the first bacterial inhibitor identified from Pseudomonas aeruginosa phage PaP3. It was also the first phage protein that interacted with the global regulator RpoS of bacteria. Our results indicated the potential value of gp70.1 in antibacterial applications. This study preliminarily revealed the biological function of gp70.1 and provided a reference for the study of other phage genes sharing similarities with orf70.1. PMID: 27725812 [PubMed - in process]

Global metabolomics reveals potential urinary biomarkers of esophageal squamous cell carcinoma for diagnosis and staging.

Wed, 12/10/2016 - 20:14
Global metabolomics reveals potential urinary biomarkers of esophageal squamous cell carcinoma for diagnosis and staging. Sci Rep. 2016 Oct 11;6:35010 Authors: Xu J, Chen Y, Zhang R, He J, Song Y, Wang J, Wang H, Wang L, Zhan Q, Abliz Z Abstract We performed a metabolomics study using liquid chromatography-mass spectrometry (LC-MS) combined with multivariate data analysis (MVDA) to discriminate global urine profiles in urine samples from esophageal squamous cell carcinoma (ESCC) patients and healthy controls (NC). Our work evaluated the feasibility of employing urine metabolomics for the diagnosis and staging of ESCC. The satisfactory classification between the healthy controls and ESCC patients was obtained using the MVDA model, and obvious classification of early-stage and advanced-stage patients was also observed. The results suggest that the combination of LC-MS analysis and MVDA may have potential applications for ESCC diagnosis and staging. We then conducted LC-MS/MS experiments to identify the potential biomarkers with large contributions to the discrimination. A total of 83 potential diagnostic biomarkers for ESCC were screened out, and 19 potential biomarkers were identified; the variations between the differences in staging using these potential biomarkers were further analyzed. These biomarkers may not be unique to ESCCs, but instead result from any malignant disease. To further elucidate the pathophysiology of ESCC, we studied related metabolic pathways and found that ESCC is associated with perturbations of fatty acid β-oxidation and the metabolism of amino acids, purines, and pyrimidines. PMID: 27725730 [PubMed - in process]

An Experimental Guideline for the Analysis of Histologically Heterogeneous Tumors by MALDI-TOF Mass Spectrometry Imaging.

Wed, 12/10/2016 - 20:14
An Experimental Guideline for the Analysis of Histologically Heterogeneous Tumors by MALDI-TOF Mass Spectrometry Imaging. Biochim Biophys Acta. 2016 Oct 7;: Authors: Lou S, Balluff B, Cleven AH, Bovée JV, McDonnell LA Abstract Mass spectrometry imaging (MSI) has been widely used for the direct molecular assessment of tissue samples and has demonstrated great potential to complement current histopathological methods in cancer research. It is now well established that tissue preparation is key to a successful MSI experiment; for histologically heterogeneous tumor tissues, other parts of the workflow are equally important to the experiment's success. To demonstrate these facets here we describe a matrix-assisted laser desorption/ionization MSI biomarker discovery investigation of high-grade, complex karyotype sarcomas, which often have histological overlap and moderate response to chemo-/radio-therapy. Multiple aspects of the workflow had to be optimized, ranging from the tissue preparation and data acquisition protocols, to the post-MSI histological staining method, data quality control, histology-defined data selection, data processing and statistical analysis. Only as a result of developing every step of the biomarker discovery workflow was it possible to identify a panel of protein signatures that could distinguish between different subtypes of sarcomas or could predict patient survival outcome. PMID: 27725306 [PubMed - as supplied by publisher]

Biochemical studies of Piper betle L Leaf Extract on Obese Treated Animal using 1H-NMR-Based Metabolomic Approach of Blood Serum Samples.

Wed, 12/10/2016 - 20:14
Biochemical studies of Piper betle L Leaf Extract on Obese Treated Animal using 1H-NMR-Based Metabolomic Approach of Blood Serum Samples. J Ethnopharmacol. 2016 Oct 7;: Authors: Abdul Ghani ZD, Husin JM, Rashid AH, Shaari K, Chik Z Abstract Piper Betle L. (PB) belongs to the Piperaceae family. The presence of a fairly large quantity of diastase in the betel leaf is deemed to play an important role in starch digestion and calls for the study of weight loss activities and metabolite profile from PB leaf extracts using metabolomics approach to be performed. PB dried leaves were extracted with 70% ethanol and the extracts were subjected to five groups of rats fed with high fat (HF) and standard diet (SD). They were then fed with the extracts in two doses and compared with a negative control group given water only according to the study protocol. The body weights and food intakes were monitored every week. At the end of the study, blood serum of the experimental animal was analysed to determine the biochemical and metabolite changes. PB treated group demonstrated inhibition of body weight gain without showing an effect on the food intake. In serum bioassay, the PB treated group (HF/PB (100mg/kg and 500mg/kg) showed an increased in glucose and cholesterol levels compared to the Standard Diet (SD/WTR) group, a decrease in LDL level and increase in HDL level when compared with High Fat Diet (HF/WTR) group. For metabolite analysis, two separation models were made to determine the metabolite changes via group activities. The best separation of PCA serum in Model 1 and 2 was achieved in principle component 1 and principle component 2. SUS-Plot model showed that HF group was characterized by high-level of glucose, glycine and alanine. Increase in the β-hydroxybutyrate level similar with SD group animals was evident in the HF/PB(500mg/kg) group. This finding suggested that the administration of 500mg/kg PB extracts leads to increase in oxidation process in the body thus maintaining the body weight and without giving an effect on the appetite even though HF was continuously consumed by the animals until the end of the studies and also a reduction in food intake, thus maintaining their body weight although they were continuously consumed HF. PMID: 27725236 [PubMed - as supplied by publisher]

Circulating angiopoietin-like protein 8 (ANGPTL8) and ANGPTL3 concentrations in relation to anthropometric and metabolic profiles in Korean children: a prospective cohort study.

Wed, 12/10/2016 - 20:14
Related Articles Circulating angiopoietin-like protein 8 (ANGPTL8) and ANGPTL3 concentrations in relation to anthropometric and metabolic profiles in Korean children: a prospective cohort study. Cardiovasc Diabetol. 2016 Jan 06;15:1 Authors: Chung HS, Lee MJ, Hwang SY, Lee HJ, Yoo HJ, Seo JA, Kim SG, Kim NH, Baik SH, Choi DS, Kim SM, Choi KM Abstract BACKGROUND: Previous studies have shown that angiopoietin-like protein 8 (ANGPTL8), also called as betatrophin, acts together with ANGPTL3 to regulate lipid metabolism, glucose metabolism, and energy homeostasis. Moreover, ANGPTL8 promotes proliferation of pancreatic β-cells and induces insulin secretion. However, there are no previous longitudinal studies in humans. METHODS: We analyzed the age- and sex-matched data of 240 normal weight and overweight Korean children from the Korean Metabolic disorders and Obesity Study in Elementary School children (K-MOSES), a prospective observational cohort study. RESULTS: At baseline, ANGPTL8 concentrations were positively associated with triglycerides (TG) (r = 0.168, P = 0.010), whereas ANGPTL3 levels were associated with fasting insulin (r = 0.248, P < 0.001) and the homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.197, P = 0.002). Although both ANGPTL8 and ANGPTL3 levels did not differ between children with normal weight and children with overweight, ANGPTL8 levels were increased in males compared to females (341.2 [267.4-436.5] vs. 270.2 [213.9-378.8] pg/ml, P = 0.001). In particular, there was no significant inter-relationship between circulating ANGPTL8 and ANGPTL3 concentrations in Korean boys and girls (r = -0.073, P = 0.265). Multivariate analysis showed that baseline ANGPTL8 concentrations were independently associated with future changes of serum TG levels in Korean children after adjusting for confounding factors after a 3 year follow-up period (r = -0.165, P = 0.016). CONCLUSIONS: This longitudinal study demonstrated for the first time that baseline ANGPTL8 levels were associated with baseline and future changes in TG levels in Korean children. PMID: 26739706 [PubMed - indexed for MEDLINE]

Metabolic footprinting for investigation of antifungal properties of Lactobacillus paracasei.

Wed, 12/10/2016 - 20:14
Related Articles Metabolic footprinting for investigation of antifungal properties of Lactobacillus paracasei. Anal Bioanal Chem. 2016 Jan;408(1):83-96 Authors: Honoré AH, Aunsbjerg SD, Ebrahimi P, Thorsen M, Benfeldt C, Knøchel S, Skov T Abstract Lactic acid bacteria with antifungal properties are applied for biopreservation of food. In order to further our understanding of their antifungal mechanism, there is an ongoing search for bioactive molecules. With a focus on the metabolites formed, bioassay-guided fractionation and comprehensive screening have identified compounds as antifungal. Although these are active, the compounds have been found in concentrations that are too low to account for the observed antifungal effect. It has been hypothesized that the formation of metabolites and consumption of nutrients during bacterial fermentations form the basis for the antifungal effect, i.e., the composition of the exometabolome. To build a more comprehensive view of the chemical changes induced by bacterial fermentation and the effects on mold growth, a strategy for correlating the exometabolomic profiles with mold growth was applied. The antifungal properties were assessed by measuring mold growth of two Penicillium strains on cell-free ferments of three strains of Lactobacillus paracasei pre-fermented in a chemically defined medium. Exometabolomic profiling was performed by reversed-phase liquid chromatography in combination with mass spectrometry in electrospray positive and negative modes. By multivariate data analysis, the three strains of Lb. paracasei were readily distinguished by the relative difference of their exometabolomes. The relative differences correlated with the relative growth of the two Penicillium strains. Metabolic footprinting proved to be a supplement to bioassay-guided fractionation for investigation of antifungal properties of bacterial ferments. Additionally, three previously identified and three novel antifungal metabolites from Lb. paracasei and their potential precursors were detected and assigned using the strategy. PMID: 26573172 [PubMed - indexed for MEDLINE]

N-glycosylation Profiling of Colorectal Cancer Cell Lines Reveals Association of Fucosylation with Differentiation and Caudal Type Homebox 1 (CDX1)/Villin mRNA Expression.

Wed, 12/10/2016 - 20:14
Related Articles N-glycosylation Profiling of Colorectal Cancer Cell Lines Reveals Association of Fucosylation with Differentiation and Caudal Type Homebox 1 (CDX1)/Villin mRNA Expression. Mol Cell Proteomics. 2016 Jan;15(1):124-40 Authors: Holst S, Deuss AJ, van Pelt GW, van Vliet SJ, Garcia-Vallejo JJ, Koeleman CA, Deelder AM, Mesker WE, Tollenaar RA, Rombouts Y, Wuhrer M Abstract Various cancers such as colorectal cancer (CRC) are associated with alterations in protein glycosylation. CRC cell lines are frequently used to study these (glyco)biological changes and their mechanisms. However, differences between CRC cell lines with regard to their glycosylation have hitherto been largely neglected. Here, we comprehensively characterized the N-glycan profiles of 25 different CRC cell lines, derived from primary tumors and metastatic sites, in order to investigate their potential as glycobiological tumor model systems and to reveal glycans associated with cell line phenotypes. We applied an optimized, high-throughput membrane-based enzymatic glycan release for small sample amounts. Released glycans were derivatized to stabilize and differentiate between α2,3- and α2,6-linked N-acetylneuraminic acids, followed by N-glycosylation analysis by MALDI-TOF(/TOF)-MS. Our results showed pronounced differences between the N-glycosylation patterns of CRC cell lines. CRC cell line profiles differed from tissue-derived N-glycan profiles with regard to their high-mannose N-glycan content but showed a large overlap for complex type N-glycans, supporting their use as a glycobiological cancer model system. Importantly, we could show that the high-mannose N-glycans did not only occur as intracellular precursors but were also present at the cell surface. The obtained CRC cell line N-glycan features were not clearly correlated with mRNA expression levels of glycosyltransferases, demonstrating the usefulness of performing the structural analysis of glycans. Finally, correlation of CRC cell line glycosylation features with cancer cell markers and phenotypes revealed an association between highly fucosylated glycans and CDX1 and/or villin mRNA expression that both correlate with cell differentiation. Together, our findings provide new insights into CRC-associated glycan changes and setting the basis for more in-depth experiments on glycan function and regulation. PMID: 26537799 [PubMed - indexed for MEDLINE]

Proteomic analyses of the interaction between the plant-growth promoting rhizobacterium Paenibacillus polymyxa E681 and Arabidopsis thaliana.

Wed, 12/10/2016 - 20:14
Related Articles Proteomic analyses of the interaction between the plant-growth promoting rhizobacterium Paenibacillus polymyxa E681 and Arabidopsis thaliana. Proteomics. 2016 Jan;16(1):122-35 Authors: Kwon YS, Lee DY, Rakwal R, Baek SB, Lee JH, Kwak YS, Seo JS, Chung WS, Bae DW, Kim SG Abstract Plant growth-promoting rhizobacteria (PGPR) facilitate the plant growth and enhance their induced systemic resistance (ISR) against a variety of environmental stresses. In this study, we carried out integrative analyses on the proteome, transcriptome, and metabolome to investigate Arabidopsis root and shoot responses to the well-known PGPR strain Paenibacillus polymyxa (P. polymyxa) E681. Shoot fresh and root dry weights were increased, whereas root length was decreased by treatment with P. polymyxa E681. 2DE approach in conjunction with MALDI-TOF/TOF analysis revealed a total of 41 (17 spots in root, 24 spots in shoot) that were differentially expressed in response to P. polymyxa E681. Biological process- and molecular function-based bioinformatics analysis resulted in their classification into seven different protein groups. Of these, 36 proteins including amino acid metabolism, antioxidant, defense and stress response, photosynthesis, and plant hormone-related proteins were up-regulated, whereas five proteins including three carbohydrate metabolism- and one amino acid metabolism-related, and one unknown protein were down-regulated, respectively. A good correlation was observed between protein and transcript abundances for the 12 differentially expressed proteins during interactions as determined by qPCR analysis. Metabolite analysis using LC-MS/MS revealed highly increased levels of tryptophan, indole-3-acetonitrile (IAN), indole-3-acetic acid (IAA), and camalexin in the treated plants. Arabidopsis plant inoculated P. polymyxa E681 also showed resistance to Botrytis cinerea infection. Taken together these results suggest that P. polymyxa E681 may promote plant growth by induced metabolism and activation of defense-related proteins against fungal pathogen. PMID: 26460066 [PubMed - indexed for MEDLINE]

Epigenetics in Cancer: A Hematological Perspective.

Tue, 11/10/2016 - 13:10
Epigenetics in Cancer: A Hematological Perspective. PLoS Genet. 2016 Oct;12(10):e1006193 Authors: Stahl M, Kohrman N, Gore SD, Kim TK, Zeidan AM, Prebet T Abstract For several decades, we have known that epigenetic regulation is disrupted in cancer. Recently, an increasing body of data suggests epigenetics might be an intersection of current cancer research trends: next generation sequencing, immunology, metabolomics, and cell aging. The new emphasis on epigenetics is also related to the increasing production of drugs capable of interfering with epigenetic mechanisms and able to trigger clinical responses in even advanced phase patients. In this review, we will use myeloid malignancies as proof of concept examples of how epigenetic mechanisms can trigger or promote oncogenesis. We will also show how epigenetic mechanisms are related to genetic aberrations, and how they affect other systems, like immune response. Finally, we will show how we can try to influence the fate of cancer cells with epigenetic therapy. PMID: 27723796 [PubMed - in process]

Renal injury in neonates: use of 'omics' for developing precision medicine in neonatology.

Tue, 11/10/2016 - 13:10
Renal injury in neonates: use of 'omics' for developing precision medicine in neonatology. Pediatr Res. 2016 Oct 10;: Authors: Joshi MS, Montgomery KA, Giannone PJ, Bauer JA, Hanna MH Abstract Preterm birth is associated with increased risks of morbidity and mortality along with increased healthcare costs. Advances in medicine have enhanced survival for preterm infants but the overall incidences of major morbidities have changed very little. Abnormal renal development is an important consequence of premature birth. Acute kidney injury (AKI) in the neonatal period is multifactorial and may increase lifetime risk of chronic kidney disease.Traditional biomarkers in newborns suffer from considerable confounders, limiting their use for early identification of AKI. There is a need to develop novel biomarkers that can identify, in real time, the evolution of renal dysfunction in an early diagnostic, monitoring and prognostic fashion. Use of 'omics', particularly metabolomics, may provide valuable information regarding functional pathways underlying AKI and prediction of clinical outcomes.The emerging knowledge generated by the application of 'omics' (genomics, proteomics, metabolomics) in neonatology provides new insights that can help to identify markers of early diagnosis, disease progression, and identify new therapeutic targets. Additionally, omics will have major implications in the field of personalized healthcare in the future. Here we will review the current knowledge of different omics technologies in neonatal-perinatal medicine including biomarker discovery, defining as yet unrecognized biologic therapeutic targets, and linking of omics to relevant standard indices and long-term outcomes. PMID: 27723726 [PubMed - as supplied by publisher]

Perturbation of metabonome of embryo/larvae zebrafish after exposure to fipronil.

Tue, 11/10/2016 - 13:10
Perturbation of metabonome of embryo/larvae zebrafish after exposure to fipronil. Environ Toxicol Pharmacol. 2016 Oct 5;48:39-45 Authors: Yan L, Gong C, Zhang X, Zhang Q, Zhao M, Wang C Abstract The escalating demand for fipronil by the increasing insects' resistance to synthetic pyrethroids placed a burden on aquatic vertebrates. Although awareness regarding the toxicity of fipronil to fish is arising, the integral alteration caused by fipronil remains unexplored. Here, we investigated on the development toxicity of fipronil and the metabolic physiology perturbation at 120h post fertilization through GC-MS metabolomics on zebrafish embryo. We observed that fipronil dose-dependently induced malformations including uninflated swim bladder and bent spine. Further, the "omic" technique hit 26 differential metabolites after exposure to fipronil and five significant signaling pathways. We speculated that changes in primary bile acid synthesis pathway and the content of saturated fatty acid in the chemical-related group indicated the liver toxicity. Pathway of Aminoacyl-tRNA biosynthesis changed by fipronil may relate to the macromolecular synthesis. Concurrently, methane metabolism pathway was also identified while the role in zebrafish needs further determination. Overall, this study revealed several new signaling pathways in fipronil-treated zebrafish embryo/larval. PMID: 27723511 [PubMed - as supplied by publisher]

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