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

Rhizobium Impacts on Seed Productivity, Quality, and Protection of Pisum sativum upon Disease Stress Caused by Didymella pinodes: Phenotypic, Proteomic, and Metabolomic Traits.

Wed, 06/12/2017 - 14:53
Related Articles Rhizobium Impacts on Seed Productivity, Quality, and Protection of Pisum sativum upon Disease Stress Caused by Didymella pinodes: Phenotypic, Proteomic, and Metabolomic Traits. Front Plant Sci. 2017;8:1961 Authors: Ranjbar Sistani N, Kaul HP, Desalegn G, Wienkoop S Abstract In field peas, ascochyta blight is one of the most common fungal diseases caused by Didymella pinodes. Despite the high diversity of pea cultivars, only little resistance has been developed until to date, still leading to significant losses in grain yield. Rhizobia as plant growth promoting endosymbionts are the main partners for establishment of symbiosis with pea plants. The key role of Rhizobium as an effective nitrogen source for legumes seed quality and quantity improvement is in line with sustainable agriculture and food security programs. Besides these growth promoting effects, Rhizobium symbiosis has been shown to have a priming impact on the plants immune system that enhances resistance against environmental perturbations. This is the first integrative study that investigates the effect of Rhizobium leguminosarum bv. viceae (Rlv) on phenotypic seed quality, quantity and fungal disease in pot grown pea (Pisum sativum) cultivars with two different resistance levels against D. pinodes through metabolomics and proteomics analyses. In addition, the pathogen effects on seed quantity components and quality are assessed at morphological and molecular level. Rhizobium inoculation decreased disease severity by significant reduction of seed infection level. Rhizobium symbiont enhanced yield through increased seed fresh and dry weights based on better seed filling. Rhizobium inoculation also induced changes in seed proteome and metabolome involved in enhanced P. sativum resistance level against D. pinodes. Besides increased redox and cell wall adjustments light is shed on the role of late embryogenesis abundant proteins and metabolites such as the seed triterpenoid Soyasapogenol. The results of this study open new insights into the significance of symbiotic Rhizobium interactions for crop yield, health and seed quality enhancement and reveal new metabolite candidates involved in pathogen resistance. PMID: 29204150 [PubMed]

Genomics of Metal Stress-Mediated Signalling and Plant Adaptive Responses in Reference to Phytohormones.

Wed, 06/12/2017 - 14:53
Related Articles Genomics of Metal Stress-Mediated Signalling and Plant Adaptive Responses in Reference to Phytohormones. Curr Genomics. 2017 Dec;18(6):512-522 Authors: Shukla A, Srivastava S, Suprasanna P Abstract Introduction: As a consequence of a sessile lifestyle, plants often have to face a number of life threatening abiotic and biotic stresses. Plants counteract the stresses through morphological and physiological adaptations, which are imparted through flexible and well-coordinated network of signalling and effector molecules, where phytohormones play important role. Hormone synthesis, signal transduction, perception and cross-talks create a complex network. Omics approaches, which include transcriptomics, genomics, proteomics and metabolomics, have opened new paths to understand such complex networks. Objective: This review concentrates on the importance of phytohormones and enzymatic expressions under metal stressed conditions. Conclusion: This review sheds light on gene expressions involved in plant adaptive and defence responses during metal stress. It gives an insight of genomic approaches leading to identification and functional annotation of genes involved in phytohormone signal transduction and perception. Moreover, it also emphasizes on perception, signalling and cross-talks among various phytohormones and other signalling components viz., Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS). PMID: 29204080 [PubMed]

Adipose tissue mitochondrial capacity associates with long-term weight loss success.

Wed, 06/12/2017 - 14:53
Related Articles Adipose tissue mitochondrial capacity associates with long-term weight loss success. Int J Obes (Lond). 2017 Dec 05;: Authors: Jokinen R, Rinnankoski-Tuikka R, Kaye S, Saarinen L, Heinonen S, Myöhänen M, Rappou E, Jukarainen S, Rissanen A, Pessia A, Velagapudi V, Virtanen KA, Pirinen E, Pietiläinen KH Abstract OBJECTIVES: We investigated whether (1) subcutaneous adipose tissue (SAT) mitochondrial capacity predicts weight loss success and (2) weight loss ameliorates obesity-related SAT mitochondrial abnormalities. METHODS: SAT biopsies were obtained from 19 clinically healthy obese subjects (BMI 34.6±2.7 kg/m2) during a weight-loss intervention (0, 5, and 12 months) and from 19 lean reference subjects (BMI 22.7±1.1 kg/m2) at baseline. Based on one-year weight loss outcome, the subjects were divided into two groups: continuous weight losers (WL, n=6) and weight regainers (WR, n=13). Main outcome measures included SAT mitochondrial pathways from transcriptomics, mitochondrial amount (mitochondrial DNA (mtDNA), Porin protein levels), mtDNA-encoded transcripts, oxidative phosphorylation (OXPHOS) proteins, and plasma metabolites of the mitochondrial branched-chain amino acid catabolism (BCAA) pathway. SAT and visceral adipose tissue (VAT) glucose uptake was measured with positron emission tomography. RESULTS: Despite similar baseline clinical characteristics, SAT in the WL group exhibited higher gene expression level of nuclear-encoded mitochondrial pathways (P=0.0224 OXPHOS, P=0.0086 tricarboxylic acid cycle, P=0.0074 fatty acid beta-oxidation and P=0.0122 BCAA), mtDNA transcript COX1 (P=0.0229) and protein level of Porin (P=0.0462) than the WR group. Many baseline mitochondrial parameters correlated with weight loss success, and with SAT and VAT glucose uptake. During weight loss, the nuclear-encoded mitochondrial pathways were downregulated, together with increased plasma metabolite levels of BCAAs in both groups. MtDNA copy number increased in the WR group at 5 months (P=0.012), but decreased to baseline level between 5 to 12 months (P=0.015). The only significant change in the WL group for mtDNA was a reduction between 5 and 12 months (P=0.004). The levels of Porin did not change in either group upon weight loss. CONCLUSIONS: Higher mitochondrial capacity in SAT predicts good long-term weight loss success. Weight loss does not ameliorate SAT mitochondrial downregulation and based on pathway expression, may paradoxically further reduce it. DATA AVAILABILITY: The transcriptomics data generated in this study have been deposited to the Gene Expression Omnibus public repository, accession number GSE103769.International Journal of Obesity accepted article preview online, 05 December 2017. doi:10.1038/ijo.2017.299. PMID: 29203860 [PubMed - as supplied by publisher]

Pitfalls in the detection of citrullination and carbamylation.

Wed, 06/12/2017 - 14:53
Related Articles Pitfalls in the detection of citrullination and carbamylation. Autoimmun Rev. 2017 Dec 01;: Authors: Verheul MK, van Veelen PA, van Delft MAM, de Ru A, Janssen GMC, Rispens T, Toes REM, Trouw LA Abstract Carbamylation and citrullination are both post-translational modifications against which (auto)antibodies can be detected in sera of rheumatoid arthritis (RA) patients. Carbamylation is the chemical modification of a lysine into a homocitrulline, whereas citrullination is an enzymatic conversion of an arginine into a citrulline. It is difficult to distinguish between the two resulting amino acids due to similarities in structure. However, differentiation between citrulline and homocitrulline is important to understand the antigens that induce antibody production and to determine which modified antigens are present in target tissues. We have observed in literature that conclusions are frequently drawn regarding the citrullination or carbamylation of proteins based on reagents that are not able to distinguish between these two modifications. Therefore, we have analyzed a wide spectrum of methods and describe here which method we consider most optimal to distinguish between citrulline and homocitrulline. We have produced several carbamylated and citrullinated proteins and investigated the specificity of (commercial) antibodies by both ELISA and western blot. Furthermore, detection methods based on chemical modifications, such as the anti-modified citrulline-"Senshu" method and also mass spectrometry were investigated for their capacity to distinguish between carbamylation and citrullination. We observed that some antibodies are able to distinguish between carbamylation and citrullination, but an overlap in reactivity is often present in the commercially available anti-citrulline antibodies. Finally, we conclude that the use of mass spectrometry is currently essential to differentiate between citrullinated and carbamylated proteins present in complex biological samples. PMID: 29203292 [PubMed - as supplied by publisher]

Transcriptomic and metabolic responses of Calotropis procera to salt and drought stress.

Wed, 06/12/2017 - 14:53
Related Articles Transcriptomic and metabolic responses of Calotropis procera to salt and drought stress. BMC Plant Biol. 2017 Dec 04;17(1):231 Authors: Mutwakil MZ, Hajrah NH, Atef A, Edris S, Sabir MJ, Al-Ghamdi AK, Sabir MJSM, Nelson C, Makki RM, Ali HM, El-Domyati FM, Al-Hajar ASM, Gloaguen Y, Al-Zahrani HS, Sabir JSM, Jansen RK, Bahieldin A, Hall N Abstract BACKGROUND: Calotropis procera is a wild plant species in the family Apocynaceae that is able to grow in harsh, arid and heat stressed conditions. Understanding how this highly adapted plant persists in harsh environments should inform future efforts to improve the hardiness of crop and forage plant species. To study the plant response to droμght and osmotic stress, we treated plants with polyethylene glycol and NaCl and carried out transcriptomic and metabolomics measurements across a time-course of five days. RESULTS: We identified a highly dynamic transcriptional response across the time-course including dramatic changes in inositol signaling, stress response genes and cytokinins. The resulting metabolome changes also involved sharp increases of myo-inositol, a key signaling molecule and elevated amino acid metabolites at later times. CONCLUSIONS: The data generated here provide a first glimpse at the expressed genome of C. procera, a plant that is exceptionally well adapted to arid environments. We demonstrate, through transcriptome and metabolome analysis that myo-inositol signaling is strongly induced in response to drought and salt stress and that there is elevation of amino acid concentrations after prolonged osmotic stress. This work should lay the foundations of future studies in adaptation to arid environments. PMID: 29202709 [PubMed - in process]

Intestinal epithelial cell caveolin 1 regulates fatty acid and lipoprotein cholesterol plasma levels.

Wed, 06/12/2017 - 14:53
Related Articles Intestinal epithelial cell caveolin 1 regulates fatty acid and lipoprotein cholesterol plasma levels. Dis Model Mech. 2017 Mar 01;10(3):283-295 Authors: Otis JP, Shen MC, Quinlivan V, Anderson JL, Farber SA Abstract Caveolae and their structural protein caveolin 1 (CAV1) have roles in cellular lipid processing and systemic lipid metabolism. Global deletion of CAV1 in mice results in insulin resistance and increases in atherogenic plasma lipids and cholesterol, but protects from diet-induced obesity and atherosclerosis. Despite the fundamental role of the intestinal epithelia in the regulation of dietary lipid processing and metabolism, the contributions of CAV1 to lipid metabolism in this tissue have never been directly investigated. In this study the cellular dynamics of intestinal Cav1 were visualized in zebrafish and the metabolic contributions of CAV1 were determined with mice lacking CAV1 in intestinal epithelial cells (CAV1IEC-KO). Live imaging of Cav1-GFP and fluorescently labeled caveolae cargos shows localization to the basolateral and lateral enterocyte plasma membrane (PM), suggesting Cav1 mediates transport between enterocytes and the submucosa. CAV1IEC-KO mice are protected from the elevation in circulating fasted low-density lipoprotein (LDL) cholesterol associated with a high-fat diet (HFD), but have increased postprandial LDL cholesterol, total free fatty acids (FFAs), palmitoleic acid, and palmitic acid. The increase in circulating FAs in HFD CAV1IEC-KO mice is mirrored by decreased hepatic FAs, suggesting a non-cell-autonomous role for intestinal epithelial cell CAV1 in promoting hepatic FA storage. In conclusion, CAV1 regulates circulating LDL cholesterol and several FA species via the basolateral PM of enterocytes. These results point to intestinal epithelial cell CAV1 as a potential therapeutic target to lower circulating FFAs and LDL cholesterol, as high levels are associated with development of type II diabetes and cardiovascular disease. PMID: 28130355 [PubMed - indexed for MEDLINE]

metabolomics; +24 new citations

Tue, 05/12/2017 - 14:33
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 2017/12/05PubMed 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.

Postnatal Subacute Benzo(a)Pyrene Exposure Caused Neurobehavioral Impairment and Metabolomic Changes of Cerebellum in the Early Adulthood Period of Sprague-Dawley Rats.

Mon, 04/12/2017 - 23:07
Postnatal Subacute Benzo(a)Pyrene Exposure Caused Neurobehavioral Impairment and Metabolomic Changes of Cerebellum in the Early Adulthood Period of Sprague-Dawley Rats. Neurotox Res. 2017 Dec 01;: Authors: Li C, Wang J, Su Q, Yang K, Chen C, Jiang X, Han T, Cheng S, Mo T, Zhang R, Peng B, Guo Y, Baker PN, Tu B, Xia Y Abstract Benzo(a)pyrene (BaP) is a widespread environmental contaminant that has been associated with neurotoxicity in mammals. It has strong toxic effects on the developing central nervous system. Cerebellum is associated with locomotor activity and anxiety behavior, but there is very little research about the toxic effects of BaP in cerebellum. The present study aims to investigate the global influence of BaP subacute exposure on the metabolome of rat cerebellum. Male neonatal rats (postnatal day 5) were divided into two groups: control group and BaP-treated group (2 mg/kg/day for 7 weeks). Open field test and transmission electron microscopy were performed to analyze neurobehavior and ultramicrostructure alteration. Gas chromatography-mass spectrometry (GC-MS) was used to analyze metabolites of the cerebellum in both groups. The results revealed that postnatal exposure to BaP promoted pathological changes in the cerebellum and increased locomotor and anxiety activities in early adulthood. Twenty differential significant metabolites were identified by multivariate statistical analysis. Further metabolic pathway impact analysis and network analysis suggested that the primary metabolic pathways affected included pathway involved in energy metabolism, methionine and cysteine metabolism, and glutathione metabolism. These findings suggest that BaP-induced cerebellum injury may be correlated with metabolic changes and provide an area to target to reduce the negative effects of BaP. PMID: 29197064 [PubMed - as supplied by publisher]

Metabolomic prediction of treatment outcome in pancreatic ductal adenocarcinoma patients receiving gemcitabine.

Mon, 04/12/2017 - 23:07
Metabolomic prediction of treatment outcome in pancreatic ductal adenocarcinoma patients receiving gemcitabine. Cancer Chemother Pharmacol. 2017 Dec 01;: Authors: Phua LC, Goh S, Tai DWM, Leow WQ, Alkaff SMF, Chan CY, Kam JH, Lim TKH, Chan ECY Abstract PURPOSE: Resistance to gemcitabine remains a key challenge in the treatment of pancreatic ductal adenocarcinoma (PDAC), necessitating the constant search for effective strategies for a priori prediction of clinical outcome. While the existing studies focused on aberration of drug disposition genes and proteins as molecular predictors of gemcitabine treatment outcomes, the metabolic aberration associated with chemoresistance in clinical PDAC has been neglected. This exploratory study investigated the potential role of tissue metabolomics in characterizing the clinical treatment outcome of gemcitabine therapy. METHODS: Surgically resected tumors from PDAC patients who underwent gemcitabine-based adjuvant chemotherapy (n = 25) were subjected to metabotyping using gas chromatography/time-of-flight mass spectrometry (GC/TOFMS). RESULTS: A partial least-squares discriminant analysis (PLS-DA) model clearly distinguished patients who had favorable survival [overall survival (OS) > 24 months] from those who exhibited poorer survival (OS < 16 months) (Q 2 = 0.302). Receiver-operating characteristic analysis demonstrated the robustness of the PLS-DA model with an area under the curve of 1. PLS-DA revealed 19 marker metabolites (e.g., lactic acid, proline, and pyroglutamate) that shed insights into the chemoresistance of gemcitabine in PDAC. Particularly, tissue levels of lactic acid complemented transcript expression levels of human equilibrative nucleoside transporter 1 in distinguishing patients according to their overall survival. CONCLUSION: This work established proof-of-principle for GC/TOFMS-based global metabotyping of PDAC and laid the foundation for future discovery of metabolic biomarkers predictive of gemcitabine resistance in PDAC chemotherapy. PMID: 29196965 [PubMed - as supplied by publisher]

Proteomics and metabolomics identify molecular mechanisms of aging potentially predisposing for chronic lymphocytic leukemia.

Mon, 04/12/2017 - 23:07
Proteomics and metabolomics identify molecular mechanisms of aging potentially predisposing for chronic lymphocytic leukemia. Mol Cell Proteomics. 2017 Dec 01;: Authors: Mayer RL, Schwarzmeier JD, Gerner MC, Bileck A, Mader JC, Meier-Menches SM, Gerner SM, Schmetterer KG, Pukrop T, Reichle A, Slany A, Gerner C Abstract B cell chronic lymphocytic leukemia (B-CLL), the most common type of leukemia in adults, is still essentially incurable despite the development of novel therapeutic strategies. This reflects the incomplete understanding of the pathophysiology of this disease. A comprehensive proteome analysis of primary human B-CLL cells and B cells from younger as well as elderly healthy donors was performed. For comparison, also the chronic B cell leukemia cell line JVM-13 was included. A principal component analysis comprising 6945 proteins separated these four groups, placing B cells of aged-matched controls between those of young donors and B-CLL patients, while identifying JVM-13 as poorly related cells. Mass spectrometric proteomics data have been made fully accessible via ProteomeXchange with identifier PXD006570-PXD006572, PXD006576, PXD006578 and PXD006589-PXD006591. Remarkably, B cells from aged controls displayed significant regulation of proteins related to stress management in mitochondria and ROS stress such as DLAT, FIS1 and NDUFAB1, and DNA repair including RAD9A, MGMT and XPA. ROS levels were indeed found significantly increased in B cells but not in T cells or monocytes from aged individuals. These alterations may be relevant for tumorigenesis and were observed similarly in B-CLL cells. In B-CLL cells, some remarkable unique features like the loss of tumor suppressor molecules PNN and JARID2, the stress-related serotonin transporter SLC6A4, and high expression of ZNF207, CCDC88A, PIGR and ID3, otherwise associated with stem cell phenotype, were determined. Alterations of metabolic enzymes were another outstanding feature in comparison to normal B cells, indicating increased beta-oxidation of fatty acids and increased consumption of glutamine. Targeted metabolomics assays corroborated these results. The present findings identify a potential proteome signature for immune senescence in addition to previously unrecognized features of B-CLL cells and suggest that aging may be accompanied by cellular reprogramming functionally relevant for predisposing B cells to transform to B-CLL cells. PMID: 29196338 [PubMed - as supplied by publisher]

Shotgun metagenomics and volatilome profile of the microbiota of fermented sausages.

Mon, 04/12/2017 - 23:07
Shotgun metagenomics and volatilome profile of the microbiota of fermented sausages. Appl Environ Microbiol. 2017 Dec 01;: Authors: Ferrocino I, Bellio A, Giordano M, Macori G, Romano A, Rantsiou K, Decastelli L, Cocolin L Abstract Changes in the microbial gene content and abundance can be analyzed to detect shifts in the microbiota composition due to the use of a starter culture in food fermentation process with the consequent shift of key metabolic pathways directly connected with product acceptance. Meat fermentation is a complex process involving microbes that metabolize the main components in meat. The breakdown of carbohydrates, proteins and lipids can lead to the formation of volatile organic compounds (VOCs) that can drastically affect the organoleptic characteristics of the final products. The present meta-analysis, performed with the shotgun DNA metagenomic approach, focuses on studying the microbiota and its gene content development in an Italian fermented sausage by using a commercial starter culture (a mix of Lactobacillus sakei and Staphylococcus xylosus), with the aim to discover the connection between microbiota and microbiome with the release of volatile metabolites during ripening.The inoculated fermentation with the starter culture limited the development of Enterobacteriaceae and reduced the microbial diversity compared to spontaneous fermentation.KEGG genes associated to the reduction of acetaldehyde to ethanol (EC:1.1.1.1), acetyl-P to acetate (EC:2.7.2.1), 2,3 butanediol to acetoin (EC:1.1.14) were found most abundant in inoculated samples (I) compared to spontaneous (S). The volatilome profiles were highly consistent with the genes abundance, elevated acetic acid (1173.85 μg/kg) ethyl acetate (251.58 μg/kg) and acetoin (1100.19 μg/kg) were observed in the presence of the starters at end of fermentation.Significant differences were found in liking among samples based on flavor and odor suggesting a higher preference by consumers for the spontaneous samples. Inoculated samples exhibited the lowest scores for the liking data, clearly associated to the highest concentration of acetic acid.IMPORTANCE We present an advance in the understanding of meat fermentation by coupling the DNA-seq metagenomics and metabolomics approaches to describe the microbial function during this process. Very few studies with this global approach have been dedicated to food but none in sausage fermentation underlying the originality of the study. The starter culture drastically affected the organoleptic properties of the products. This finding underlines the importance of starter culture selection that takes into consideration functional characteristics of the microorganism, in order to optimize production efficiency and product quality. PMID: 29196291 [PubMed - as supplied by publisher]

Differentiation of commercial ground beef products and correlation between metabolites and sensory attributes: A metabolomic approach.

Mon, 04/12/2017 - 23:07
Differentiation of commercial ground beef products and correlation between metabolites and sensory attributes: A metabolomic approach. Food Res Int. 2016 Dec;90:298-306 Authors: Jiang T, Bratcher CL Abstract Three traditional grinds (commodity products) and 7 non-traditional grinds (branded products) were obtained to investigate the metabolites in ground beef associated with beef flavor or off-flavor. Three packaging methods were used: traditional overwrap, modified atmosphere package, and clear plastic retail chub. Samples were collected for sensory evaluation and metabolic profiling utilizing LC/MS. Principal component analysis was conducted for classification of grind source or packaging method. Partial least squares regression was applied to investigate the relationship between metabolic data and sensory data. Grass-fed beef and natural beef products were clearly separated from the other grinds. A total of 576 metabolites were registered. Thirty-three compounds were selected as the most important ones differentiating beef grinds. Twenty-two compounds were selected as the most important ones associated with beef flavor and off-flavor. In conclusion, metabolomic approach was effective to determine the most important compounds associated with certain quality characteristics of beef. PMID: 29195885 [PubMed - in process]

metabolomics; +16 new citations

Sat, 02/12/2017 - 19:18
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 2017/12/02PubMed 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

Sat, 02/12/2017 - 13:08
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 2017/12/02PubMed 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; +24 new citations

Fri, 01/12/2017 - 15:31
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 2017/12/01PubMed 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; +60 new citations

Wed, 29/11/2017 - 14:17
60 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 2017/11/29PubMed 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.

The Target of Rapamycin kinase affects biomass accumulation and cell cycle progression by altering carbon/nitrogen balance in synchronized Chlamydomonas reinhardtii cells.

Sun, 26/11/2017 - 03:38
The Target of Rapamycin kinase affects biomass accumulation and cell cycle progression by altering carbon/nitrogen balance in synchronized Chlamydomonas reinhardtii cells. Plant J. 2017 Nov 24;: Authors: Jüppner J, Mubeen U, Leisse A, Caldana C, Wiszniewski A, Steinhauser D, Giavalisco P Abstract Several metabolic processes tightly regulate growth and biomass accumulation. A highly conserved protein complex containing the Target of Rapamycin (TOR) kinase is known to integrate intra- and extra-cellular stimuli controlling nutrient allocation and hence cellular growth. Although, several functions of TOR have been described in various heterotrophic eukaryotes, our understanding lags far behind in photosynthetic organisms. In the present investigation, we used the model alga Chlamydomonas reinhardtii to conduct a time-resolved analysis of molecular and physiological features throughout the diurnal cycle after TOR inhibition. Detailed examination of the cell cycle phases revealed that growth is not only repressed by 50% but also that significant, nonlinear delays in the progression can be observed. By using metabolomics analysis, we elucidated that the growth repression was mainly driven by differential carbon partitioning between anabolic and catabolic processes. Accordingly, the time-resolved analysis illustrated that metabolic processes including amino acid-, starch- and triacylglycerol synthesis, as well RNA degradation, were redirected within minutes of TOR inhibition. Here especially the high accumulation of nitrogen containing compounds indicated that an active TOR kinase controls the carbon to nitrogen balance of the cell, which is responsible for biomass accumulation, growth and cell cycle progression. This article is protected by copyright. All rights reserved. PMID: 29172247 [PubMed - as supplied by publisher]

Microdosing, isotopic labeling, radiotracers and metabolomics: relevance in drug discovery, development and safety.

Sun, 26/11/2017 - 03:38
Microdosing, isotopic labeling, radiotracers and metabolomics: relevance in drug discovery, development and safety. Bioanalysis. 2017 Nov 24;: Authors: Wotherspoon AT, Safavi-Naeini M, Banati RB Abstract This review discusses the use of stable ((13)C, (2)D) or radioactive isotopes ((14)C, (11)C, (18)F, (131)I, (64)Cu, (68)Ga) incorporated into the molecular structure of new drug entities for the purpose of pharmacokinetic or -dynamic studies. Metabolite in safety testing requires the administration of pharmacologically active doses. In such studies, radiotracers find application mainly in preclinical animal investigations, whereby LC-MS/MS is used to identify metabolite structure and drug-related effects. In contrast, first-in-human metabolite studies have to be carried out at nonpharmacological doses not exceeding 100 μg (microdose), which is generally too low for metabolite detection by LC-MS/MS. This short-coming can be overcome by specific radio- or isotopic labeling of the drug of interest and measurements using accelerator mass spectroscopy, single-photon emission computed tomography and positron emission tomography. Such combined radioisotope-based approaches permit Phase 0, first-in-human metabolite study. PMID: 29171759 [PubMed - as supplied by publisher]

[Analysis of influencing factors of secondary metabolites contents in cultivated Polygala tenuifolia].

Sun, 26/11/2017 - 03:38
[Analysis of influencing factors of secondary metabolites contents in cultivated Polygala tenuifolia]. Zhongguo Zhong Yao Za Zhi. 2017 Aug;42(16):3167-3177 Authors: Pu YJ, Wang DD, Yan Y, Tian HL, Peng B, Qin XM, Ma CG, Du CH, Hu BX, Zhang FS Abstract This work was launched to explore the effect of habitat and growth year on the secondary metabolites contents of cultivated Polygala tenuifolia. The samples of cultivated P. tenuifolia were analyzed by ultra-high performance liquid chromatography(UPLC)-quadrupole time-of-flight mass spectrometry(Q-TOF MS), and the obtained data were analyzed using multiple statistical analysis and cluster analysis. The results showed that compared with growth year, habitat is a main influencing factor which affected the secondary metabolites contents of P. tenuifolia. The contents of sucrose esters and oligosacchride multi-esters are greatly dependent on the habitat (the sample-AG with high levels of components of tenuifoliside B and tenuifoliside C, and the sample-FY with high levels of 3,6'-disinapoyl sucrose, tenuifoliose S, tenuifoliose L, and tenuifoliose V). There is no obvious effect of habitat and growth year on xanthone. The contents of triterpene saponins are greatly dependent on the growth year, and the content of parts of triterpene saponins increased as time goes on.The result indicated that the effect of habitat and growth year on different types of secondary metabolites is not completely equivalent. This study will contribute to the breeding of P. tenuifolia and amendment of current commodity criteria. PMID: 29171237 [PubMed - in process]

Joining the Dots between Omics and Environmental Management.

Sun, 26/11/2017 - 03:38
Joining the Dots between Omics and Environmental Management. Integr Environ Assess Manag. 2017 Nov 24;: Authors: Leung KMY Abstract With the rapid advancement of DNA sequencing technologies and substantial reduction of their running costs, environmental genomics and transcriptomics become more affordable and popular in environmental toxicology. In parallel, there are also speedy improvements of mass spectrometry and nuclear magnetic resonance spectrometry, enabling high-throughput analyses of proteins and metabolites in biological samples and promoting research studies in proteomics and metabolomics. By applying these high throughput omics technologies, researchers can quickly generate an unprecedentedly vast amount of biological data that may be useful to environmental management. However, the current pace of applying omics information in environmental management is still very slow, and lags well behind the rapid development of omics-based research. This commentary, therefore, timely calls for joint efforts to increase this pace and join the dots between omics and environmental management, turning omics into practical tools. Herein, I explore how omics can contribute to risk assessment and management of chemicals, and recommend what we can do to facilitate and promote the use of omics information in environmental management. This article is especially dedicated to my role model, mentor and friend, Dr. Peter M. Chapman (1951-2017) who sadly passed away on 26 September 2017. This article is protected by copyright. All rights reserved. PMID: 29171160 [PubMed - as supplied by publisher]

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