PubMed

Related Articles Different classes of anti-modified protein antibodies are induced on exposure to antigens expressing only one type of modification. Ann Rheum Dis. 2019 07;78(7):908-916 Authors: Kampstra ASB, Dekkers JS, Volkov M, Dorjée AL, Hafkenscheid L, Kempers AC, van Delft M, Kissel T, Reijm S, Janssen GMC, van Veelen PA, Bang H, Huizinga TWJ, Trouw LA, van der Woude D, Toes REM Abstract OBJECTIVES: Autoantibodies against post-translationally modified proteins (anti-modified protein antibodies or AMPAs) are a hallmark of rheumatoid arthritis (RA). A variety of classes of AMPAs against different modifications on proteins, such as citrullination, carbamylation and acetylation, have now been described in RA. At present, there is no conceptual framework explaining the concurrent presence or mutual relationship of different AMPA responses in RA. Here, we aimed to gain understanding of the co-occurrence of AMPA by postulating that the AMPA response shares a common 'background' that can evolve into different classes of AMPAs. METHODS: Mice were immunised with modified antigens and analysed for AMPA responses. In addition, reactivity of AMPA purified from patients with RA towards differently modified antigens was determined. RESULTS: Immunisation with carbamylated proteins induced AMPAs recognising carbamylated proteins and also acetylated proteins. Similarly, acetylated proteins generated (autoreactive) AMPAs against other modifications as well. Analysis of anti-citrullinated protein antibodies from patients with RA revealed that these also display reactivity to acetylated and carbamylated antigens. Similarly, anti-carbamylated protein antibodies showed cross-reactivity against all three post-translational modifications. CONCLUSIONS: Different AMPA responses can emerge from exposure to only a single type of modified protein. These findings indicate that different AMPA responses can originate from a common B-cell response that diversifies into multiple distinct AMPA responses and explain the presence of multiple AMPAs in RA, one of the hallmarks of the disease. PMID: 31151934 [PubMed - indexed for MEDLINE]

36 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 2020/03/04PubMed 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.

36 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 2020/03/04PubMed 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.

35 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 2020/03/03PubMed 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.

35 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 2020/03/03PubMed 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.

Retinal disease: How to use proteomics to speed up diagnosis and metabolomics to slow down degeneration. EBioMedicine. 2020 Feb 26;53:102687 Authors: Hurley JB, Chao JR PMID: 32113163 [PubMed - as supplied by publisher]

The phenolic profile extracted from the desiccation-tolerant medicinal shrub Myrothamnus flabellifolia using Natural Deep Eutectic Solvents varies according to the solvation conditions. Phytochemistry. 2020 Feb 26;173:112323 Authors: Bentley J, Olsen EK, Moore JP, Farrant JM Abstract Natural Deep Eutectic Solvents (NaDES) have been proposed as designer solvents for the green extraction of bioactive products from plants. Myrothamnus flabellifolia is a desiccation-tolerant medicinal shrub that has been widely studied for its phenolic properties; however, a NaDES-based approach for the extraction of phenolics has not been tested in this species. Our aim was thus to evaluate the extraction of phenolics from M. flabellifolia using four different NaDES with differing acidities using a non-targeted liquid chromatography-quantitative time-of-flight-tandem mass spectrometry (LC-QTOF-MS/MS) metabolomics approach. Anthocyanin pigments were quantified using targeted high-performance LC. Leaf material from M. flabellifolia was extracted in four different NaDES solutions (sucrose-fructose-glucose; proline-malic acid; sucrose-citric acid; and glucose-choline chloride), and the results were subjected to multivariate statistical analysis to evaluate the phenolic profiles of the different NaDES extracts. The NaDES were effective at extracting phenolic compounds from M. flabellifolia and also exhibited specificity in the suites of phenolics that they extracted, as indicated by principal component analysis. Using partial least squares-discriminant analysis, we were able to identify the phenolics that were most differentially abundant between the extracts, and a heatmap provided an indication of the types of phenolics that were extracted by the different NaDES. Furthermore, the NaDES also extracted several compounds not previously detected in M. flabellifolia using conventional organic solvents, demonstrating their use in compound discovery. The NaDES also differentially targeted anthocyanins, with the more acidic NaDES extracting higher quantities of anthocyanins and polymeric pigments. A green chemistry-based extraction technique using NaDES can thus effectively target phenolics in M. flabellifolia and offers a promising solution for future phytochemical investigations in medicinal plants using a highly efficient non-toxic solvent system that can be tailored to target particular compounds. PMID: 32113067 [PubMed - as supplied by publisher]

Baicalein protects PC12 cells from Aβ25-35-induced cytotoxicity via inhibition of apoptosis and metabolic disorders. Life Sci. 2020 Feb 26;:117471 Authors: Gao L, Zhou F, Wang KX, Zhou YZ, Du GH, Qin XM Abstract AIMS: This study aimed to explore the protective effects and possible mechanisms of baicalein on Aβ25-35-induced toxicity. MAIN METHODS: Thioflavin-T (Th-T) dye was used to determine the effects of baicalein on Aβ25-35 aggregation in vitro. PC12 cells were stimulated with Aβ25-35, then the effects of baicalein on apoptosis, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP), mitochondrial respiratory complex I, reactive oxygen species (ROS) and nitric oxide (NO) levels were determined. Moreover, LC-MS metabolomics approach was used to detect metabolic changes induced by baicalein in Aβ25-35-injured PC12 cells. KEY FINDINGS: The results showed that baicalein could inhibit the aggregation of Aβ25-35 in vitro. Furthermore, pretreatment with baicalein significantly prevented Aβ25-35-induced cell apoptosis, as manifested by increasing the levels of MMP, ATP and mitochondrial respiratory complex I, decreasing the contents of ROS and NO. LC-MS metabolomics revealed that baicalein can regulate 5 metabolites, mainly involving two metabolic pathways, arginine and proline metabolism, nicotinate and nicotinamide metabolism. SIGNIFICANCE: Our study revealed that baicalein has a protective effect on Aβ25-35-induced neurotoxicity in PC12 cells, which may be related to inhibition of apoptosis and metabolic disorders. PMID: 32112868 [PubMed - as supplied by publisher]

Related Articles A UV-B-responsive glycosyltransferase, OsUGT706C2, modulates flavonoid metabolism in rice. Sci China Life Sci. 2020 Feb 25;: Authors: Zhang F, Guo H, Huang J, Yang C, Li Y, Wang X, Qu L, Liu X, Luo J Abstract Although natural variations in rice flavonoids exist, and biochemical characterization of a few flavonoid glycosyltransferases has been reported, few studies focused on natural variations in tricin-lignan-glycosides and their underlying genetic basis. In this study, we carried out metabolic profiling of tricin-lignan-glycosides and identified a major quantitative gene annotated as a UDP-dependent glycosyltransferase OsUGT706C2 by metabolite-based genome-wide association analysis. The putative flavonoid glycosyltransferase OsUGT706C2 was characterized as a flavonoid 7-O-glycosyltransferas in vitro and in vivo. Although the in vitro enzyme activity of OsUGT706C2 was similar to that of OsUGT706D1, the expression pattern and induced expression profile of OsUGT706C2 were very different from those of OsUGT706D1. Besides, OsUGT706C2 was specifically induced by UV-B. Constitutive expression of OsUGT706C2 in rice may modulate phenylpropanoid metabolism at both the transcript and metabolite levels. Furthermore, overexpressing OsUGT706C2 can enhance UV-B tolerance by promoting ROS scavenging in rice. Our findings might make it possible to use the glycosyltransferase OsUGT706C2 for crop improvement with respect to UV-B adaptation and/or flavonoid accumulation, which may contribute to stable yield. PMID: 32112268 [PubMed - as supplied by publisher]

Related Articles Haploid genetic screens identify SPRING/C12ORF49 as a determinant of SREBP signaling and cholesterol metabolism. Nat Commun. 2020 Feb 28;11(1):1128 Authors: Loregger A, Raaben M, Nieuwenhuis J, Tan JME, Jae LT, van den Hengel LG, Hendrix S, van den Berg M, Scheij S, Song JY, Huijbers IJ, Kroese LJ, Ottenhoff R, van Weeghel M, van de Sluis B, Brummelkamp T, Zelcer N Abstract The sterol-regulatory element binding proteins (SREBP) are central transcriptional regulators of lipid metabolism. Using haploid genetic screens we identify the SREBP Regulating Gene (SPRING/C12ORF49) as a determinant of the SREBP pathway. SPRING is a glycosylated Golgi-resident membrane protein and its ablation in Hap1 cells, Hepa1-6 hepatoma cells, and primary murine hepatocytes reduces SREBP signaling. In mice, Spring deletion is embryonic lethal yet silencing of hepatic Spring expression also attenuates the SREBP response. Mechanistically, attenuated SREBP signaling in SPRINGKO cells results from reduced SREBP cleavage-activating protein (SCAP) and its mislocalization to the Golgi irrespective of the cellular sterol status. Consistent with limited functional SCAP in SPRINGKO cells, reintroducing SCAP restores SREBP-dependent signaling and function. Moreover, in line with the role of SREBP in tumor growth, a wide range of tumor cell lines display dependency on SPRING expression. In conclusion, we identify SPRING as a previously unrecognized modulator of SREBP signaling. PMID: 32111832 [PubMed - as supplied by publisher]

Related Articles Bacterial glycogen provides short-term benefits in changing environments. Appl Environ Microbiol. 2020 Feb 28;: Authors: Sekar K, Linker SM, Nguyen J, Grünhagen A, Stocker R, Sauer U Abstract Changing nutritional conditions challenge microbes and shape their evolutionary optimization. Here we investigated the role of glycogen in dynamic physiological adaptation of Escherichia coli to fluctuating nutrients following carbon starvation using real-time metabolomics. We found significant metabolic activity remaining after the depletion of environmental glucose that was linked to a rapid utilization of intracellular glycogen. Glycogen was depleted by 80% within minutes of glucose starvation and similarly replenished within minutes of glucose availability. These fast timescales of glycogen utilization correspond to the short-term benefits that glycogen provided to cells undergoing various physiological transitions. Cells capable of utilizing glycogen exhibited shorter lag times than glycogen mutants when starved between different carbon sources. The ability to utilize glycogen was also important for the transition between planktonic and biofilm lifestyles and enabled increased glucose uptake during pulses of limited glucose availability. While wild-type and mutant strains exhibited comparable growth rates in steady environments, mutants deficient in glycogen utilization grew more poorly in environments that fluctuated on minute-scales between carbon availability and starvation. Altogether, these results highlight an underappreciated role of glycogen to rapidly provide carbon and energy in changing environments, thereby increasing survival and competition capabilities in fluctuating and nutrient poor conditions.ImportanceNothing is constant in life and microbes in particular have to adapt to frequent and rapid environmental changes. Here we demonstrate that the internal storage polymer glycogen plays a crucial role for such dynamic adaptations by using real-time metabolomics and single cell imaging. Glycogen depletes within minutes of glucose starvation and similarly replenishes within minutes of glucose availability. Cells capable of utilizing glycogen exhibited shorter lag times than glycogen mutants when starved between different carbon sources. While wild- type and mutant strains exhibited comparable growth rates in steady environments, mutants deficient in glycogen utilization grew more poorly in environments that fluctuated on minute- scales between carbon availability and starvation. These results highlight an underappreciated role of glycogen to rapidly provide carbon and energy in changing environments, thereby increasing survival and competition capabilities in fluctuating and nutrient poor conditions. PMID: 32111592 [PubMed - as supplied by publisher]

Related Articles Enterotype identification and its influence on regulating the duodenum metabolism in chickens. Poult Sci. 2020 Mar;99(3):1515-1527 Authors: Yuan Z, Yan W, Wen C, Zheng J, Yang N, Sun C Abstract Enterotypes are used to describe clusters of specific gut microbial community structures, but few reports exist on the identification of enterotypes in poultry. In addition, there is incomplete understanding on the role of the foregut microbiota in the digestion and absorption of nutrients in poultry. Thus, this study aimed to identify the duodenal enterotypes by examining microbial communities from 206 broilers using 16S rRNA high-throughput sequencing and explore the effects of enterotypes on phenotypic performance and nutrient metabolism with metabolomics. The duodenal microbial communities of the broiler population were partitioned into 3 enterotypes (ET1, ET2, and ET3), and significant differences were observed in α-diversity among the enterotypes (P < 0.01). At the genus level, the ET1 group was over-represented by Bacteroides (9.8%) and Escherichia-Shigella (8.9%), the ET2 group was over-represented by Ochrobactrum (19.4%) and Rhodococcus (14.7%), and the ET3 group was over-represented by Bacillus (23.4%) and Akkermansia (16.2%). The relative abundance of the dominant taxa of each enterotype was significantly higher than that in the other 2 enterotypes (P < 0.01). The results showed that Ochrobactrum and Rhodococcus were positively correlated with cellobiose, alpha-D-glucose, D-mannose, and D-allose (r = 0.429, 0.435, 0.482, and 0.562, respectively; all P < 0.05). Rhodococcus was also positively correlated with tridecanoic acid and glycerol 1-myristate (r = 0.655 and 0.489, respectively; all P < 0.01). In terms of phenotype, the triglyceride level in the ET2 group was significantly higher than that in the ET1 group (P < 0.05), and the subcutaneous fat thickness and abdominal fat weight in the ET2 group were the highest (P > 0.05). Taken together, these results confirmed the presence of enterotypes in broilers and found that the dominant microbes in broilers of the ET2 group might play a major role in the degradation and utilization of plant polysaccharides, which may have an impact on the serum triglyceride level and fat deposition in broilers. These findings lay a foundation for further studies on the gut microbial interactions with the metabolism in broilers and the regulation of the gut microbiota to promote growth and well-being in broilers. PMID: 32111319 [PubMed - as supplied by publisher]

Related Articles A snapshot of microbial diversity and function in an undisturbed sugarcane bagasse pile. BMC Biotechnol. 2020 Feb 28;20(1):12 Authors: Gebbie L, Dam TT, Ainscough R, Palfreyman R, Cao L, Harrison M, O'Hara I, Speight R Abstract BACKGROUND: Sugarcane bagasse is a major source of lignocellulosic biomass, yet its economic potential is not fully realised. To add value to bagasse, processing is needed to gain access to the embodied recalcitrant biomaterials. When bagasse is stored in piles in the open for long periods it is colonised by microbes originating from the sugarcane, the soil nearby or spores in the environment. For these microorganisms to proliferate they must digest the bagasse to access carbon for growth. The microbial community in bagasse piles is thus a potential resource for the discovery of useful and novel microbes and industrial enzymes. We used culturing and metabarcoding to understand the diversity of microorganisms found in a uniquely undisturbed bagasse storage pile and screened the cultured organisms for fibre-degrading enzymes. RESULTS: Samples collected from 60 to 80 cm deep in the bagasse pile showed hemicellulose and partial lignin degradation. One hundred and four microbes were cultured from different layers and included a high proportion of oleaginous yeast and biomass-degrading fungi. Overall, 70, 67, 70 and 57% of the microbes showed carboxy-methyl cellulase, xylanase, laccase and peroxidase activity, respectively. These percentages were higher in microbes selectively cultured from deep layers, with all four activities found for 44% of these organisms. Culturing and amplicon sequencing showed that there was less diversity and therefore more selection in the deeper layers, which were dominated by thermophiles and acid tolerant organisms, compared with the top of pile. Amplicon sequencing indicated that novel fungi were present in the pile. CONCLUSIONS: A combination of culture-dependent and independent methods was successful in exploring the diversity in the bagasse pile. The variety of species that was found and that are known for biomass degradation shows that the bagasse pile was a valuable selective environment for the identification of new microbes and enzymes with biotechnological potential. In particular, lignin-modifying activities have not been reported previously for many of the species that were identified, suggesting future studies are warranted. PMID: 32111201 [PubMed - as supplied by publisher]

Related Articles Untargetted Metabolomic Exploration of the Mycobacterium tuberculosis Stress Response to Cinnamon Essential Oil. Biomolecules. 2020 Feb 26;10(3): Authors: Sieniawska E, Sawicki R, Golus J, Georgiev MI Abstract The antimycobacterial activity of cinnamaldehyde has already been proven for laboratory strains and for clinical isolates. What is more, cinnamaldehyde was shown to threaten the mycobacterial plasma membrane integrity and to activate the stress response system. Following promising applications of metabolomics in drug discovery and development we aimed to explore the mycobacteria response to cinnamaldehyde within cinnamon essential oil treatment by untargeted liquid chromatography-mass spectrometry. The use of predictive metabolite pathway analysis and description of produced lipids enabled the evaluation of the stress symptoms shown by bacteria. This study suggests that bacteria exposed to cinnamaldehyde could reorganize their outer membrane as a physical barrier against stress factors. They probably lowered cell wall permeability and inner membrane fluidity, and possibly redirected carbon flow to store energy in triacylglycerols. Being a reactive compound, cinnamaldehyde may also contribute to disturbances in bacteria redox homeostasis and detoxification mechanisms. PMID: 32111061 [PubMed - as supplied by publisher]

Related Articles Metabolomics Analysis Reveals the Alkali Tolerance Mechanism in Puccinellia tenuiflora Plants Inoculated with Arbuscular Mycorrhizal Fungi. Microorganisms. 2020 Feb 26;8(3): Authors: Yang C, Zhao W, Wang Y, Zhang L, Huang S, Lin J Abstract Soil alkalization is a major environmental threat that affects plant distribution and yield in northeastern China. Puccinellia tenuiflora is an alkali-tolerant grass species that is used for salt-alkali grassland restoration. However, little is known about the molecular mechanisms by which arbuscular mycorrhizal fungi (AMF) enhance P. tenuiflora responses to alkali stress. Here, metabolite profiling in P. tenuiflora seedlings with or without arbuscular mycorrhizal fungi (AMF) under alkali stress was conducted using liquid chromatography combined with time-of-flight mass spectrometry (LC/TOF-MS). The results showed that AMF colonization increased seedling biomass under alkali stress. In addition, principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) demonstrated that non-AM and AM seedlings showed different responses under alkali stress. A heat map analysis showed that the levels of 88 metabolites were significantly changed in non-AM seedlings, but those of only 31 metabolites were significantly changed in AM seedlings. Moreover, the levels of a total of 62 metabolites were significantly changed in P. tenuiflora seedlings after AMF inoculation. The results suggested that AMF inoculation significantly increased amino acid, organic acid, flavonoid and sterol contents to improve osmotic adjustment and maintain cell membrane stability under alkali stress. P. tenuiflora seedlings after AMF inoculation produced more plant hormones (salicylic acid and abscisic acid) than the non-AM seedlings, probably to enhance the antioxidant system and facilitate ion balance under stress conditions. In conclusion, these findings provide new insights into the metabolic mechanisms of P. tenuiflora seedlings with arbuscular mycorrhizal fungi under alkali conditions and clarify the role of AM in the molecular regulation of this species under alkali stress. PMID: 32110985 [PubMed - as supplied by publisher]

Related Articles Metabolic Profiling of Glucose-Fed Metabolically Active Resting Zymomonas mobilis Strains. Metabolites. 2020 Feb 26;10(3): Authors: Fuchino K, Kalnenieks U, Rutkis R, Grube M, Bruheim P Abstract Zymomonas mobilis is the most efficient bacterial ethanol producer and its physiology is potentially applicable to industrial-scale bioethanol production. However, compared to other industrially important microorganisms, the Z. mobilis metabolome and adaptation to various nutritional and genetic perturbations have been poorly characterized. For rational metabolic engineering, it is essential to understand how central metabolism and intracellular redox balance are maintained in Z. mobilis under various conditions. In this study, we applied quantitative mass spectrometry-based metabolomics to explore how glucose-fed non-growing Z. mobilis Zm6 cells metabolically adapt to change of oxygen availability. Mutants partially impaired in ethanol synthesis (Zm6 adhB) or oxidative stress response (Zm6 cat) were also examined. Distinct patterns of adaptation of central metabolite pools due to the change in cultivation condition and between the mutants and Zm6 reference strain were observed. Decreased NADH/NAD ratio under aerobic incubation corresponded to higher concentrations of the phosphorylated glycolytic intermediates, in accordance with predictions of the kinetic model of Entner-Doudoroff pathway. The effects on the metabolite pools of aerobic to anaerobic transition were similar in the mutants, yet less pronounced. The present data on metabolic plasticity of non-growing Z. mobilis cells will facilitate the further metabolic engineering of the respective strains and their application as biocatalysts. PMID: 32110884 [PubMed - as supplied by publisher]

20 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 2020/02/29PubMed 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.

27 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 2020/02/28PubMed 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.

23 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 2020/02/27PubMed 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.

33 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 2020/02/26PubMed 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.