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

Thu, 23/08/2018 - 16:31
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 2018/08/23PubMed 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

Thu, 23/08/2018 - 13:30
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 2018/08/23PubMed 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.

Early mechanical leaf removal in Merlot (Vitis vinifera L.) enhances fruit technological maturity and alters the flavonoid metabolomic profile.

Wed, 22/08/2018 - 12:31
Early mechanical leaf removal in Merlot (Vitis vinifera L.) enhances fruit technological maturity and alters the flavonoid metabolomic profile. J Agric Food Chem. 2018 Aug 21;: Authors: VanderWeide J, Medina-Meza IG, Frioni T, Sivilotti P, Falchi R, Sabbatini P Abstract Removal of basal leaves near bloom inevitably affects grapevine balance and cluster microclimate conditions, improving fruit quality. Mechanization of this practice allows growers to save time and resources, but, to our knowledge, has not yet been compared with manual application in a cool climate region where seasonal temperature accumulation frequently limits fruit technological maturity and phenolic ripening in red Vitis vinifera cultivars. In our research, berry sugar concentration was highest in the pre-bloom mechanical treatment (PB-ME). Furthermore, metabolomics analysis revealed that PB-ME favored the accumulation of significantly more di-substituted anthocyanins and flavonols and OH-substituted anthocyanins compared to the manual application. Given that vine balance was similar between treatments, increased ripening in PB-ME is likely due to enhanced microclimate conditions, and higher carbon partitioning through a younger canopy containing basal leaf fragments proximal to fruit. This information provides an important strategy to consistently ripen red Vitis vinifera cultivars in cool climates. PMID: 30130400 [PubMed - as supplied by publisher]

HR-MAS NMR-based metabolomics reveals metabolic changes in lung of mice infected with P. aeruginosa consistent with the degree of disease severity, and is a powerful evaluation tool for new treatment.

Wed, 22/08/2018 - 12:31
HR-MAS NMR-based metabolomics reveals metabolic changes in lung of mice infected with P. aeruginosa consistent with the degree of disease severity, and is a powerful evaluation tool for new treatment. J Proteome Res. 2018 Aug 21;: Authors: Le Gouellec A, Moyne O, Meynet E, Toussaint B, Fauvelle F Abstract Pseudomonas aeruginosa is a critical pathogen for human health, due to increased resistances to antibiotics and to nosocomial infections. There is an urgent need for tools allowing to better understand mechanisms underlying the disease processes and to evaluate new therapeutic strategies with animal models. Here, we used a novel approach, applying high resolution magic angle spinning nuclear magnetic resonance spectroscopy (HRMAS NMR) directly to lung biopsies of mice to better understand the impact of infection on the tissue at a molecular level. Mice were infected with two P. aeruginosa strains of different virulence levels. Statistical analysis applied to HRMAS NMR data allowed us to build a multivariate discriminant model to distinguish the lungs' metabolic profiles of mice infected or not. Moreover, a second model was built to appreciate the degree of severity of infection, demonstrating sufficient sensitivity of HRMAS NMR based metabolomics to investigate this type of infection. The metabolic features that discriminate infection statuses are dominated by some key differentially expressed metabolites which are related respectively to bacterial carbon metabolism (glycerophosphocholine) and to septic hypoxic stress response of host (succinate). Finally, in order to get closer to clinical and diagnosis issues, we proposed to build simple logistic regression models to predict the infection status on the basis of only one metabolite intensity. Thus, we have demonstrated that Succinate intensity could discriminate the infected/non-infected status infection with a sensibility of 89% and a specificity of 95%, and leucine/isoleucine intensity could predict the severe/not severe status of infection with a sensibility of 100% and a specificity of 95%. We also looked for the interest of this model in order to predict the efficacy of anti-P. aeruginosa treatment. By HRMAS metabolomics analysis of lungs infected with P. aeruginosa after vaccination, we demonstrated that this model could be an useful tool to predict the efficacy of new anti-P. aeruginosa drugs. This metabolomics approach could therefore be useful both for the definition of biomarkers of severity of infection and for an earlier characterization of therapeutic efficacy. PMID: 30129763 [PubMed - as supplied by publisher]

Trends in herbgenomics.

Wed, 22/08/2018 - 12:31
Related Articles Trends in herbgenomics. Sci China Life Sci. 2018 Aug 14;: Authors: Xin T, Zhang Y, Pu X, Gao R, Xu Z, Song J Abstract From Shen Nong's Herbal Classic (Shennong Bencao Jing) to the Compendium of Materia Medica (Bencao Gangmu) and the first scientific Nobel Prize for the mainland of China, each milestone in the historical process of the development of traditional Chinese medicine (TCM) involves screening, testing and integrating. After thousands of years of inheritance and development, herbgenomics (bencaogenomics) has bridged the gap between TCM and international advanced omics studies, promoting the application of frontier technologies in TCM. It is a discipline that uncovers the genetic information and regulatory networks of herbs to clarify their molecular mechanism in the prevention and treatment of human diseases. The main theoretical system includes genomics, functional genomics, proteomics, transcriptomics, metabolomics, epigenomics, metagenomics, synthetic biology, pharmacogenomics of TCM, and bioinformatics, among other fields. Herbgenomics is mainly applicable to the study of medicinal model plants, genomic-assisted breeding, herbal synthetic biology, protection and utilization of gene resources, TCM quality evaluation and control, and TCM drug development. Such studies will accelerate the application of cutting-edge technologies, revitalize herbal research, and strongly promote the development and modernization of TCM. PMID: 30128965 [PubMed - as supplied by publisher]

Metabolomics analysis of Pseudomonas chlororaphis JK12 algicidal activity under aerobic and micro-aerobic culture condition.

Wed, 22/08/2018 - 12:31
Related Articles Metabolomics analysis of Pseudomonas chlororaphis JK12 algicidal activity under aerobic and micro-aerobic culture condition. AMB Express. 2018 Aug 20;8(1):131 Authors: Kim J, Lyu XM, Lee JJL, Zhao G, Chin SF, Yang L, Chen WN Abstract Utilization of algicidal bacteria as a biological agent have been receiving significant interest for controlling harmful algal blooms. While various algicidal bacterial strains have been identified, limited studies have explored the influence of bacterial culture conditions on its algicidal activity. Here, the effect of oxygen on the algicidal activity of a novel bacterium JK12, against a model diatom, Phaeodactylum tricornutum (P. tricornutum) was studied. Strain JK12 showed high algicidal activity against P. tricornutum and was identified as Pseudomonas chlororaphis (P. chlororaphis) by 16S ribosomal RNA gene analysis. JK12 culture supernatant exhibited strong algicidal activity while washed JK12 cells showed no obvious activity, indicating that JK12 indirectly attacks algae by secreting extracellular algicidal metabolites. Micro-aerobic culture condition dramatically enhanced the algicidal activity of JK12 by 50%, compared to that cultured under aerobic condition in 24 h. Extracellular metabolomic profiling of JK12 using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry analysis revealed significantly higher amounts of allantoic acid, urocanic acid, cytidine 2',3'-cyclic phosphate, uridine 2',3'-cyclic phosphate, and chlorinated tryptophan in the micro-aerobic culture. This is the first report to demonstrate the important role of oxygen on the algicidal activity of a non-pathogenic strain P. chlororaphis. In addition, the metabolomics analysis provided insights into the algicidal mechanism of P. chlororaphis. PMID: 30128639 [PubMed]

De novo NAD+ biosynthetic impairment in acute kidney injury in humans.

Wed, 22/08/2018 - 12:31
Related Articles De novo NAD+ biosynthetic impairment in acute kidney injury in humans. Nat Med. 2018 Aug 20;: Authors: Poyan Mehr A, Tran MT, Ralto KM, Leaf DE, Washco V, Messmer J, Lerner A, Kher A, Kim SH, Khoury CC, Herzig SJ, Trovato ME, Simon-Tillaux N, Lynch MR, Thadhani RI, Clish CB, Khabbaz KR, Rhee EP, Waikar SS, Berg AH, Parikh SM Abstract Nicotinamide adenine dinucleotide (NAD+) extends longevity in experimental organisms, raising interest in its impact on human health. De novo NAD+ biosynthesis from tryptophan is evolutionarily conserved yet considered supplanted among higher species by biosynthesis from nicotinamide (NAM). Here we show that a bottleneck enzyme in de novo biosynthesis, quinolinate phosphoribosyltransferase (QPRT), defends renal NAD+ and mediates resistance to acute kidney injury (AKI). Following murine AKI, renal NAD+ fell, quinolinate rose, and QPRT declined. QPRT+/- mice exhibited higher quinolinate, lower NAD+, and higher AKI susceptibility. Metabolomics suggested an elevated urinary quinolinate/tryptophan ratio (uQ/T) as an indicator of reduced QPRT. Elevated uQ/T predicted AKI and other adverse outcomes in critically ill patients. A phase 1 placebo-controlled study of oral NAM demonstrated a dose-related increase in circulating NAD+ metabolites. NAM was well tolerated and was associated with less AKI. Therefore, impaired NAD+ biosynthesis may be a feature of high-risk hospitalizations for which NAD+ augmentation could be beneficial. PMID: 30127395 [PubMed - as supplied by publisher]

Metabolic profiles of cysteine, methionine, glutamate, glutamine, arginine, aspartate, asparagine, alanine and glutathione in Streptococcus thermophilus during pH-controlled batch fermentations.

Wed, 22/08/2018 - 12:31
Related Articles Metabolic profiles of cysteine, methionine, glutamate, glutamine, arginine, aspartate, asparagine, alanine and glutathione in Streptococcus thermophilus during pH-controlled batch fermentations. Sci Rep. 2018 Aug 20;8(1):12441 Authors: Qiao Y, Liu G, Leng C, Zhang Y, Lv X, Chen H, Sun J, Feng Z Abstract Elucidating the amino acid (AA) metabolism patterns of Streptococcus thermophilus has important effects on the precise design of nitrogen sources for high-cell-density culture. Transcriptomics and metabolomics were combined to reveal the cysteine, methionine, glutamate, glutamine, arginine, aspartate, asparagine and alanine metabolic pathways in S. thermophilus MN-ZLW-002, including glutathione. The changes in the synthesis, consumption and concentration of AAs and their metabolites, as well as regulatory genes with time were revealed. The metabolism of L-cysteine, L-glutamate, L-aspartate and L-alanine generated some potential functional metabolites. The metabolism of methionine and glutamate generated potential harmful metabolites. S. thermophilus MN-ZLW-002 can synthesize glutathione. Some potential functional metabolites have similar biological functions, indicating that S. thermophilus can resist environmental stresses through multiple mechanisms. The expression of some key genes in synthesis pathway of AA indicated that cysteine, methionine, asparagine, aspartate, arginine and lysine were insufficient or imbalance between nutrient components. The accumulation of large amounts of AA metabolites might be the primary cause of the overconsumption of AAs and influence the growth of S. thermophilus. The present study revealed the metabolic profiles of abovementioned AAs as well as those of regulatory genes and metabolites. These results were beneficial to the precise design of nitrogen sources and regulation of functional metabolites for the high-cell-density culture of S. thermophilus. PMID: 30127376 [PubMed - in process]

One Way to Achieve Germination: Common Molecular Mechanism Induced by Ethylene and After-Ripening in Sunflower Seeds.

Wed, 22/08/2018 - 12:31
Related Articles One Way to Achieve Germination: Common Molecular Mechanism Induced by Ethylene and After-Ripening in Sunflower Seeds. Int J Mol Sci. 2018 Aug 20;19(8): Authors: Xia Q, Saux M, Ponnaiah M, Gilard F, Perreau F, Huguet S, Balzergue S, Langlade N, Bailly C, Meimoun P, Corbineau F, El-Maarouf-Bouteau H Abstract Dormancy is an adaptive trait that blocks seed germination until the environmental conditions become favorable for subsequent vegetative plant growth. Seed dormancy is defined as the inability to germinate in favorable conditions. Dormancy is alleviated during after-ripening, a dry storage period, during which dormant (D) seeds unable to germinate become non-dormant (ND), able to germinate in a wide range of environmental conditions. The treatment of dormant seeds with ethylene (D/ET) promotes seed germination, and abscisic acid (ABA) treatment reduces non-dormant (ND/ABA) seed germination in sunflowers (Helianthus annuus). Metabolomic and transcriptomic studies have been performed during imbibition to compare germinating seeds (ND and D/ET) and low-germinating seeds (D and ND/ABA). A PCA analysis of the metabolites content showed that imbibition did not trigger a significant change during the first hours (3 and 15 h). The metabolic changes associated with germination capacity occurred at 24 h and were related to hexoses, as their content was higher in ND and D/ET and was reduced by ABA treatment. At the transcriptional level, a large number of genes were altered oppositely in germinating, compared to the low-germinating seeds. The metabolomic and transcriptomic results were integrated in the interpretation of the processes involved in germination. Our results show that ethylene treatment triggers molecular changes comparable to that of after-ripening treatment, concerning sugar metabolism and ABA signaling inhibition. PMID: 30127315 [PubMed - in process]

A Comparative Metabolomics Analysis Reveals the Tissue-Specific Phenolic Profiling in Two Acanthopanax Species.

Wed, 22/08/2018 - 12:31
Related Articles A Comparative Metabolomics Analysis Reveals the Tissue-Specific Phenolic Profiling in Two Acanthopanax Species. Molecules. 2018 Aug 20;23(8): Authors: Wu KX, Liu J, Liu Y, Guo XR, Mu LQ, Hu XH, Tang ZH Abstract Acanthopanax senticosus (Rupr. Maxim.) Harms (ASH) and Acanthopanax sessiliflorus (Rupr. Maxim.) Seem (ASS), are members of the Araliaceae family, and both are used in Asian countries. These herbals have drawn much attention in recent years due to their strong biological activity, with innocuity and little side effects. However, the common and distinct mode of compound profiles between ASH and ASS is still unclear. In this study, a high performance liquid chromatograph-mass spectrometry (HPLC-MS) method was developed to simultaneously quantify the seven major active compounds, including protocatechuate, eleutheroside B, eleutheroside E, isofraxidin, hyperoside, kaempferol and oleanolic acid. Then the targeted metabolomics were conducted to identify 19 phenolic compounds, with tight relation to the above mentioned active compounds, including nine C6C3C6-type, six C6C3-type and four C6C1-type in the two Acanthopanax species studied here. The results showed that the seven active compounds presented a similar trend of changes in different tissues, with more abundant accumulation in roots and stems for both plants. From the view of plant species, the ASH plants possess higher abundance of compounds, especially in the tissues of roots and stems. For phenolics, the 19 phenols detected here could be clearly grouped into five main clusters based on their tissue-specific accumulation patterns. Roots are the tissue for the most abundance of their accumulations. C6C3C6-type compounds are the most widely existing type in both plants. In conclusion, the tissue- and species-specificity in accumulation of seven active compounds and phenolics were revealed in two Acanthopanax species. PMID: 30127238 [PubMed - in process]

Assessment of high fat diet-induced fatty liver in medaka.

Wed, 22/08/2018 - 12:31
Related Articles Assessment of high fat diet-induced fatty liver in medaka. Biol Open. 2018 Aug 20;: Authors: Fujisawa K, Takami T, Fukui Y, Nagatomo T, Saeki I, Matsumoto T, Hidaka I, Yamamoto N, Okamoto T, Furutani-Seiki M, Sakaida I Abstract Fatty liver, which has been continuously growing in the number of patients, is the most common liver disease. For detailed analysis, a useful model of fatty liver is desired and fish is considered as a candidate of the models. We assessed direct observation of the liver, which is the most conventional method for the non-invasive analysis of the progression in fatty liver. By using transparent medaka, changes in fat deposition in the liver were able to be observed. An analysis of the assessment of the progression in fatty liver using Ultrasound showed a significant increase in echo intensity, which indicates that this is a useful examination method. In addition, we clarified a metabolite profile of the liver in medaka fed a high fat diet (HFD), which had not been shown in detail. This medaka model allowing non-invasive and repetitive assessment is a useful model for the analysis of diseases causing fatty liver in which changes in detailed metabolites are identified. PMID: 30127096 [PubMed - as supplied by publisher]

Molecular biological methods in environmental engineering.

Wed, 22/08/2018 - 12:31
Related Articles Molecular biological methods in environmental engineering. Water Environ Res. 2018 Oct 01;90(10):1371-1391 Authors: Li C, Pulin Z, Wei L, Wei D, Jia O, Chang CC Abstract Environmental bioremediation technologies are undoubtedly more economical and environmental friendly, and present a good application prospect. Microorganisms can be used to monitor environmental changes for their quickly respond to environmental changes. Microbiological molecular biology methods have attracted more and more attention from human beings, and their applications in the environment is also expanding. Genomics, transcriptomics, proteomics, and metabolomics are four major molecular biology techniques. This review summarizes application of molecular biological methods in environmental engineering in 2017. The summary includes methods for DNA, RNA, and protein extraction, the application of four major technologies in the environmental field, and commonly used methods for in situ monitoring in the environment, including fluorescence in situ hybridization, real-time quantitative PCR, and amplicons sequencing technology. PMID: 30126487 [PubMed - in process]

UPLC-QTOF/MS-Based Metabolomics Applied for the Quality Evaluation of Four Processed Panax ginseng Products.

Wed, 22/08/2018 - 12:31
Related Articles UPLC-QTOF/MS-Based Metabolomics Applied for the Quality Evaluation of Four Processed Panax ginseng Products. Molecules. 2018 Aug 17;23(8): Authors: Lee JW, Ji SH, Choi BR, Choi DJ, Lee YG, Kim HG, Kim GS, Kim K, Lee YH, Baek NI, Lee DY Abstract In the food industry and herbal markets, it is critical to control the quality of processed Panax ginseng products. In this study, ultra-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UPLC-QTOF/MS)-based metabolomics was applied for the quality evaluation of white ginseng (WG), tae-geuk ginseng (TG), red ginseng (RG), and black ginseng (BG). Diverse metabolites including ginsenosides were profiled by UPLC-QTOF/MS, and the datasets of WG, TG, RG, and BG were then subjected to multivariate analyses. In principal component analysis (PCA), four processed ginseng products were well-differentiated, and several ginsenosides were identified as major components of each product. S-plot also characterized the metabolic changes between two processed ginseng products, and the major ginsenosides of each product were found as follows: WG (M-Rb1, M-Rb2, M-Rc, Re, Rg1), TG (Rb2, Rc, Rd, Re, Rg1), RG (Rb1, Rb2, Rc, Rd, Re, Rg1), and BG (Rd, Rk1, Rg5, Rg3). Furthermore, the quantitative contents of ginsenosides were evaluated from the four processed ginseng products. Finally, it was indicated that the proposed metabolomics approach was useful for the quality evaluation and control of processed ginseng products. PMID: 30126124 [PubMed - in process]

Application of LC-MS-Based Global Metabolomic Profiling Methods to Human Mental Fatigue.

Wed, 22/08/2018 - 12:31
Related Articles Application of LC-MS-Based Global Metabolomic Profiling Methods to Human Mental Fatigue. Anal Chem. 2016 12 06;88(23):11293-11296 Authors: Chen Z, Xu X, Zhang J, Liu Y, Xu X, Li L, Wang W, Xu H, Jiang W, Wang Y Abstract Mental fatigue is characterized by a reduced capacity for work and a loss of capacity to respond to stimulation and is usually accompanied by a feeling of tiredness and drowsiness. Mental fatigue at work is a serious problem and can raise safety concerns especially in the transportation system. It is believed that mental fatigue is a direct or contributing cause of road and air related accidents and incidents. Psychological studies indicate that fatigue results in reduced work efficiency, alertness, and impaired mental performance. However, its underlying biochemical mechanisms are poorly understood. We hypothesized that the human body is an integrated system, and mental fatigue results in changes not only in psychology but also in biochemistry of the human body. These biochemical changes are detectable in metabolites. We employed global metabolomic profiling methods to screen biochemical changes that occur with mental fatigue in air traffic controllers (ATCs) in civil aviation. A total of 45, all male, ATCs (two batches) were recruited as two mental fatigue groups and 23 executive staff acted as a control group for this study. The volunteers' urine samples were collected before and after their work. The samples were analyzed with liquid chromatography/mass spectrometry equipped with a polar, a weak polar, and a nonpolar column, respectively. Three candidate biomarkers were selected on the basis of statistical significance, coefficient of variance, and compared with data of the three groups. The results suggest that urine metabolites may provide a complete new clue from biochemistry to understand, monitor, and manage human mental fatigue. PMID: 27934122 [PubMed - indexed for MEDLINE]

metabolomics; +16 new citations

Tue, 21/08/2018 - 15:03
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 2018/08/21PubMed 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

Tue, 21/08/2018 - 12:02
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 2018/08/21PubMed 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.

Follicular Dynamics of Glycerophospholipid and Sphingolipid Metabolisms in Polycystic Ovary Syndrome Patients.

Mon, 20/08/2018 - 14:30
Related Articles Follicular Dynamics of Glycerophospholipid and Sphingolipid Metabolisms in Polycystic Ovary Syndrome Patients. J Steroid Biochem Mol Biol. 2018 Aug 16;: Authors: Liu L, Yin TL, Chen Y, Li Y, Yin L, Ding J, Yang J, Feng HL Abstract Polycystic ovary syndrome (PCOS) is a common heterogeneous disease, affecting up to 5-10% women at reproductive age. Although PCOS patients could produce morphologically normal metaphase II oocytes undergoing assisted reproductive techniques (ART), oocyte developmental competence and embryo development have been impaired in following in-vitro fertilization (IVF) steps. Follicular fluid (FF) provides a variety of information in oocyte environment when oocytes grow. In the present work, based on ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS), the metabolic signatures of PCOS FF have been compared with healthy women using untargeted metabolomics approach. Significant abundance differences of a series of glycerolipid, glycerophospholipids, sphingolipids, and carboxylic acids have been discovered. Among them, reduced levels of phosphatidylglycerolphosphate (PGP) and a triglyceride (TG) were highly related to the lower fertilization rate in PCOS; increased abundance of lysoPE and decreased amount of PC were significantly correlated with LH/FSH (ratio of luteinizing hormone to follicle stimulating hormone). Some metabolites, including decreased sphingolipids, glycerophospholipids, and fluctuated fatty acyls, also performed close relationship with other ART and clinical results. We concluded that dysfunctions in the metabolism of glycerolipid, glycerophospholipid, sphingolipid, and glycosphingolipid biosynthesis in PCOS patients' follicles play a non-ignorable role in declining the 2 pronuclei (PN) fertilization rate during IVF procedure. PMID: 30121347 [PubMed - as supplied by publisher]

Effect of deletion of a trichothecene toxin regulatory gene on the secondary metabolism transcriptome of the saprotrophic fungus Trichoderma arundinaceum.

Mon, 20/08/2018 - 14:30
Related Articles Effect of deletion of a trichothecene toxin regulatory gene on the secondary metabolism transcriptome of the saprotrophic fungus Trichoderma arundinaceum. Fungal Genet Biol. 2018 Aug 16;: Authors: Lindo L, McCormick SP, Cardoza RE, Brown DW, Kim HS, Alexander NJ, Proctor RH, Gutiérrez S Abstract Trichothecenes are terpenoid toxins produced by multiple fungal species with diverse lifestyles. In these fungi, the trichothecene biosynthetic gene cluster (tri) includes a gene encoding a Cys2His2 Zn-finger protein (TRI6). Analyses of plant pathogenic Fusarium species indicate that tri6 regulates tri gene expression. Here, we analyzed TRI6 function in the saprotrophic fungus Trichoderma arundinaceum, which produces the antimicrobial trichothecene harzianum A (HA). Deletion of the TRI6-encodinggene, tri6, blocked HA production and reduced expression of tri genes, and mevalonate biosynthetic genes required for synthesis of farnesyl diphosphate (FPP), the primary metabolite that feeds into trichothecene biosynthesis. In contrast, tri6 deletion did not affect expression of ergosterol biosynthetic genes required for synthesis of ergosterol from FPP, but did increase ergosterol production, perhaps because increased levels of FPP were available for ergosterol synthesis in the absence of trichothecene production. RNA-seq analyses indicated that genes in 10 of 49 secondary metabolite (SM) biosynthetic gene clusters in T. arundinaceum exhibited increased expression and five exhibited reduced expression in a tri6 deletion mutant (Δtri6). Despite the metabolic and transcriptional changes, Δtri6 mutants were not reduced in their ability to inhibit growth of fungal plant pathogens. Our results indicate that T. arundinaceum TRI6 regulates expression of both tri and mevalonate pathway genes. It remains to be determined whether the effects of tri6 deletion on expression of other SM clusters resulted because TRI6 can bind to promoter regions in the clusters or because trichothecene production affects other SM pathways. PMID: 30121242 [PubMed - as supplied by publisher]

Bile acid metabolites in early pregnancy and risk of gestational diabetes in Chinese women: A nested case-control study.

Sun, 19/08/2018 - 14:00
Related Articles Bile acid metabolites in early pregnancy and risk of gestational diabetes in Chinese women: A nested case-control study. EBioMedicine. 2018 Aug 14;: Authors: Li J, Huo X, Cao YF, Li SN, Du Z, Shao P, Leng J, Zhang C, Sun XY, Ma RCW, Fang ZZ, XilinYang Abstract BACKGROUND: Bile acid metabolism plays an important role in metabolism but it is uncertain whether bile acid metabolites in early pregnancy are associated with risk of gestational diabetes mellitus (GDM). METHODS: We organized a 1:1 case-control study nested in a prospective cohort of 22,302 pregnant women recruited from 2010 to 2012 in China: 243 women with GDM were matched with 243 non-GDM controls on age (±1 year). Conditional logistic regression and restricted cubic spline were used to examine full-range associations of bile acid metabolites with GDM. FINDINGS: All the 9 detectable bile acids were inversely associated with the risk of GDM, among them, 8 in nonlinear and one in largely linear manners in multivariable analysis. Glycoursodeoxycholic acid (GUDCA) at ≤0.07 nmol/mL and deoxycholic acid (DCA) at ≤0.28 nmol/mL had threshold effects and their decreasing levels below the cutoff points were associated with rapid rises in the risk of GDM. In traditional risk factor model, the stepwise procedure identified that GUDCA ≤ 0.07 nmol/mL and DCA ≤ 0.280 nmol/mL were still significant (OR: 6.84, 95%CI: 1.10-42.48 & 2.06, 1.26-3.37), while other bile acids were not. Inclusion of the two bile acids in the model increased the area under operating characteristic's curve from 0.69 to 0.76 (95% CI: 0.71-0.80) (P < .05). INTERPRETATION: Serum GUDCA ≤ 0.07 nmol/mL and DCA ≤ 0.28 nmol/mL in early pregnancy were independently associated with increased risk of GDM in Chinese pregnant women. FUNDING: Talent Recruitment Scheme grant of Tianjin Medical University and National Key Research and Development Program, etc. PMID: 30120081 [PubMed - as supplied by publisher]

Intestinal bitter taste receptor activation alters hormone secretion and imparts metabolic benefits.

Sun, 19/08/2018 - 14:00
Related Articles Intestinal bitter taste receptor activation alters hormone secretion and imparts metabolic benefits. Mol Metab. 2018 Aug 04;: Authors: Kok BP, Galmozzi A, Littlejohn NK, Albert V, Godio C, Kim W, Kim SM, Bland JS, Grayson N, Fang M, Meyerhof W, Siuzdak G, Srinivasan S, Behrens M, Saez E Abstract OBJECTIVES: Extracts of the hops plant have been shown to reduce weight and insulin resistance in rodents and humans, but elucidation of the mechanisms responsible for these benefits has been hindered by the use of heterogeneous hops-derived mixtures. Because hop extracts are used as flavoring agents for their bitter properties, we hypothesized that bitter taste receptors (Tas2rs) could be mediating their beneficial effects in metabolic disease. Studies have shown that exposure of cultured enteroendocrine cells to bitter tastants can stimulate release of hormones, including glucagon-like peptide 1 (GLP-1). These findings have led to the suggestion that activation of Tas2rs may be of benefit in diabetes, but this tenet has not been tested. Here, we have assessed the ability of a pure derivative of a hops isohumulone with anti-diabetic properties, KDT501, to signal through Tas2rs. We have further used this compound as a tool to systematically assess the impact of bitter taste receptor activation in obesity-diabetes. METHODS: KDT501 was tested in a panel of bitter taste receptor signaling assays. Diet-induced obese mice (DIO) were dosed orally with KDT501 and acute effects on glucose homeostasis determined. A wide range of metabolic parameters were evaluated in DIO mice chronically treated with KDT501 to establish the full impact of activating gut bitter taste signaling. RESULTS: We show that KDT501 signals through Tas2r108, one of 35 mouse Tas2rs. In DIO mice, acute treatment stimulated GLP-1 secretion and enhanced glucose tolerance. Chronic treatment caused weight and fat mass loss, increased energy expenditure, enhanced glucose tolerance and insulin sensitivity, normalized plasma lipids, and induced broad suppression of inflammatory markers. Chronic KDT501 treatment altered enteroendocrine hormone levels and bile acid homeostasis and stimulated sustained GLP-1 release. Combined treatment with a dipeptidyl peptidase IV inhibitor amplified the incretin-based benefits of this pure isohumulone. CONCLUSIONS: Activation of Tas2r108 in the gut results in a remodeling of enteroendocrine hormone release and bile acid metabolism that ameliorates multiple features of metabolic syndrome. Targeting extraoral bitter taste receptors may be useful in metabolic disease. PMID: 30120064 [PubMed - as supplied by publisher]

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