134 results on '"Schauer, N."'
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2. Porcine intestinal yeast species, Kazachstania slooffiae, a new potential protein source with favourable amino acid composition for animals
- Author
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Urubschurov, V., Büsing, K., Souffrant, W.‐B., Schauer, N., and Zeyner, A.
- Published
- 2018
- Full Text
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3. Systems Biology: A Renaissance of the Top-down Approach for Plant Analysis
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Carrari, F., Schauer, N., Willmitzer, L., Fernie, A. R., Nagata, Toshiyuki, editor, Lörz, Horst, editor, Widholm, Jack M., editor, Saito, Kazuki, editor, Dixon, Richard A., editor, and Willmitzer, Lothar, editor
- Published
- 2006
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4. The influence of pressure during solidification of high pressure die cast aluminium telecommunications components
- Author
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Dargusch, Matthew S., Dour, G., Schauer, N., Dinnis, C.M., and Savage, G.
- Published
- 2006
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5. Reactive astrocytes and activated microglial cells express EAAT1, but not EAAT2, reflecting a neuroprotective potential following ischaemia
- Author
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Beschorner, R, Simon, P, Schauer, N, Mittelbronn, M, Schluesener, H J, Trautmann, K, Dietz, K, and Meyermann, R
- Published
- 2007
6. The outer membrane Omp85‐like protein P39 influences metabolic homeostasis in mature Arabidopsis thaliana
- Author
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Hsueh, Y.‐C., primary, Nicolaisen, K., additional, Gross, L. E., additional, Nöthen, J., additional, Schauer, N., additional, Vojta, L., additional, Ertel, F., additional, Koch, I., additional, Ladig, R., additional, Fulgosi, H., additional, Fernie, A. R., additional, and Schleiff, E., additional
- Published
- 2018
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7. Porcine intestinal yeast species,Kazachstania slooffiae, a new potential protein source with favourable amino acid composition for animals
- Author
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Urubschurov, V., primary, Büsing, K., additional, Souffrant, W.-B., additional, Schauer, N., additional, and Zeyner, A., additional
- Published
- 2017
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8. The mitochondrial eletron transfer flavoprotein complex is essential for survival of Arabidopsis in extended darkness
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Ishizaki, K, Schauer, N, Larson, T, Graham, I, Fernie, A, Leaver, C, and Biology, Society for Experimental
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Plant Sciences ,Biology - Abstract
In mammals, the electron transfer flavoprotein (ETF) is a heterodimeric protein composed of two subunits, α and β, that is responsible for the oxidation of at least nine mitochondrial matrix flavoprotein dehydrogenases. Electrons accepted by ETF are further transferred to the main respiratory chain via the ETF ubiquinone oxide reductase (ETFQO). Sequence analysis of the unique Arabidopsis homologues of two subunits of ETF revealed their high similarity to both subunits of the mammalian ETF. Yeast two-hybrid experiments showed that the Arabidopsis ETFα and ETFβ can form a heteromeric protein. Isolation and characterization of two independent T-DNA insertional Arabidopsis mutants of the ETFβ gene revealed accelerated senescence and early death compared to wild-type during extended darkness. Futhermore in contrast to wild-type, the etfb mutants demonstrated a significant accumulation of several amino acids, isovaleryl CoA and phytanoyl CoA during dark-induced carbohydrate deprivation. These phenotypic characteristics of etfb mutants are broadly similar to those that we observed previously in Arabidopsis etfqo mutants, suggesting functional association between ETF and ETFQO in Arabidopsis, and confirming the essential roles of the ETF/ETFQO electron transfer complex in the catabolism of leucine and involvement in the chlorophyll degradation pathway activated during dark-induced carbohydrate deprivation.
- Published
- 2016
9. Porcine intestinal yeast species, <italic>Kazachstania slooffiae</italic>, a new potential protein source with favourable amino acid composition for animals.
- Author
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Urubschurov, V., Büsing, K., Souffrant, W.‐B., Schauer, N., and Zeyner, A.
- Subjects
SWINE nutrition ,YEAST as feed ,AMINO acids in animal nutrition ,GUT microbiome ,GAS chromatography - Abstract
Summary: There is little information about
Kazachstania slooffiae which dominates among other yeasts in the pigs’ intestine. Therefore, the aims of this study were to characterise the yeast cell contents and to investigate which nitrogen sources, organic acids and alcohols may be utilised or produced by this species. The results showed that,K. slooffiae could use urea, ammonium sulphate, peptides and single amino acids and produce thereby ethanol and formic acid. However, this yeast did not metabolise amino acids, lactic, butyric, propionic and acetic acids as sole carbon source. Using a global metabolite profiling approach employing gas chromatography and high‐resolution liquid chromatography mass spectrometry, was found that the amount of peptides and dehydroascorbic acid considerably increased in the fermentation residues after yeast cultivation. It is noteworthy that the cells ofK. slooffiae had higher contents of nitrogen and total amino acids (especially lysine) than the cells of nutritional yeast (Saccharomyces cerevisiae ). This study indicates that due to potential production of peptides and formic acid in the intestinal tract,K. slooffiae might have an impact on the gut health. Moreover, from a nutritional standpoint, the cells of this yeast can be a good source of protein with useful amino acid composition for animal. [ABSTRACT FROM AUTHOR]- Published
- 2018
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10. Bilan à deux ans de l’équipe mobile du Réseau Santé Géronto 4 du Val-de-Marne
- Author
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Schauer, N., Cottin, D., and Lesfargues, E.
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- 2010
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11. Systems Biology: A Renaissance of the Top-down Approach for Plant Analysis
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Carrari, F., primary, Schauer, N., additional, Willmitzer, L., additional, and Fernie, A. R., additional
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12. Whole-cell response of the pennate diatom Phaeodactylum tricornutum to iron starvation
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Allen, A. E., LaRoche, Julie, Maheswari, U., Lommer, Markus, Schauer, N., Lopez, P. J., Finazzi, G., Fernie, A. R., Bowler, C., Allen, A. E., LaRoche, Julie, Maheswari, U., Lommer, Markus, Schauer, N., Lopez, P. J., Finazzi, G., Fernie, A. R., and Bowler, C.
- Abstract
Marine primary productivity is iron (Fe)-limited in vast regions of the contemporary oceans, most notably the high nutrient low chlorophyll (HNLC) regions. Diatoms often form large blooms upon the relief of Fe limitation in HNLC regions despite their prebloom low cell density. Although Fe plays an important role in controlling diatom distribution, the mechanisms of Fe uptake and adaptation to low iron availability are largely unknown. Through a combination of nontargeted transcriptomic and metabolomic approaches, we have explored the biochemical strategies preferred by Phaeodactylum tricornutum at growth-limiting levels of dissolved Fe. Processes carried out by components rich in Fe, such as photosynthesis, mitochondrial electron transport, and nitrate assimilation, were down-regulated. Our results show that this retrenchment is compensated by nitrogen (N) and carbon (C) reallocation from protein and carbohydrate degradation, adaptations to chlorophyll biosynthesis and pigment metabolism, removal of excess electrons by mitochondrial alternative oxidase (AOX) and non-photochemical quenching (NPQ), and augmented Fe-independent oxidative stress responses. Iron limitation leads to the elevated expression of at least three gene clusters absent from the Thalassiosira pseudonana genome that encode for components of iron capture and uptake mechanisms.
- Published
- 2008
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13. The metabolic response of heterotrophic Arabidopsis cells to oxidative stress.
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Baxter, C.J., Redestig, H., Schauer, N., Repsilber, D., Patil, Kiran Raosaheb, Nielsen, Jens, Selbig, J., Liu, J., Fernie, A.R, Sweetlove, L.J, Baxter, C.J., Redestig, H., Schauer, N., Repsilber, D., Patil, Kiran Raosaheb, Nielsen, Jens, Selbig, J., Liu, J., Fernie, A.R, and Sweetlove, L.J
- Published
- 2007
14. Clinical presentation of rupture of the left-ventricular free wall after myocardial infarction: report of five cases with successful surgical repair
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C. Schwarz, Pachinger O, Ng Ck, C Punzengruber, Schauer N, and Hartl P
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Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,Chest Pain ,medicine.medical_treatment ,Hemopericardium ,Myocardial rupture ,Pericardial effusion ,Severity of Illness Index ,Pericardial Effusion ,Syncope ,Pseudoaneurysm ,Cardiac tamponade ,Cause of Death ,medicine ,Humans ,Myocardial infarction ,Aged ,Heart Rupture, Post-Infarction ,Ultrasonography ,Heart Failure ,business.industry ,Suture Techniques ,Mitral valve replacement ,Electrocardiography in myocardial infarction ,Middle Aged ,medicine.disease ,Surgery ,Cardiac Tamponade ,Treatment Outcome ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Rupture of the left-ventricular free wall may not always result in immediate irreversible hemodynamic collapse. We report a series of five patients (4 male, 1 female; age 59-79 years) successfully operated for postinfarction free-wall rupture with good long-term results. Two patients presented with syncopy and acute tamponade three days after an acute myocardial infarction. In two patients with atypical chest pain and congestive heart failure, a large pericardial effusion and an extreme localized thinning of a myocardial scar region was seen several weeks after an uncomplicated myocardial infarct. In one patient a pseudoaneurysm was detected, which developed asymptomatically within three weeks after a posterior myocardial infarct. In all cases myocardial rupture was suspected after an echocardiographic examination. At surgery a hemopericardium and a localized rupture site were found. The surgical procedure included closure of the defect by direct suture or patch, CABG in 3 cases, and mitral valve replacement in one patient. The postoperative course was uneventful, only one patient needed IABP for 24 hours. Three patients returned to NYHA functional class I, one patient to class II, and one patient to class III. The latter patient died of heart failure 17 months postoperatively, and the other patients are still alive 4,18,24, and 26 months postoperatively. Thus clinical representation of left-ventricular free-wall rupture after myocardial infarction can be highly variable. But close cooperation between experienced echocardiographers and surgeons may allow successful corrections with good long term-results.
- Published
- 1996
15. Heterologous expression of a ketohexokinase in potato plants leads to inhibited rates of photosynthesis, severe growth retardation and abnormal leaf development
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Geigenberger, P., Regierer, B., Lytovchenko, A., Leisse, A., Schauer, N., Springer, F., Kossmann, J., Fernie, A.R., Geigenberger, P., Regierer, B., Lytovchenko, A., Leisse, A., Schauer, N., Springer, F., Kossmann, J., and Fernie, A.R.
- Abstract
In the present paper we investigated the effect of heterologous expression of a rat liver ketohexokinase in potato (Solanum tuberosum L.) plants with the aim of investigating the role of fructose 1-phosphate in plant metabolism. Plants were generated that contained appreciable activity of ketohexokinase but did not accumulate fructose 1-phosphate. They were, however, characterised by a severe growth retardation and abnormal leaf development. Studies of (14)CO(2) assimilation and metabolism, and of the levels of photosynthetic pigments, revealed that these lines exhibited restricted photosynthesis. Despite this fact, the levels of starch and soluble sugars remained relatively constant. Analysis of intermediates of starch and sucrose biosynthesis revealed large increases in the triose phosphate and fructose 1,6-bisphosphate pools but relatively unaltered levels of inorganic phosphate and 3-phosphoglycerate, and these lines were also characterised by an accumulation of glyceraldehyde. The transformants neither displayed consistent changes in the activities of Calvin cycle enzymes nor in enzymes of sucrose synthesis but displayed a metabolic profile partially reminiscent of that brought about by end-product limitation, but most likely caused by an inhibition of photosynthesis brought about by the accumulation of glyceraldehyde. Analysis of the metabolite contents in lamina and vein fractions of the leaf, and of the enzymes of carbohydrate oxidation indicate that the phloem-enriched veins of ketohexokinase-expressing leaves tend toward hypoxia and indicate a problem of phloem transport.
- Published
- 2004
16. O010 PROTEIN PULSE FEEDING IMPROVES LEAN MASS IN MALNOURISHED HOSPITALIZED ELDERLY PATIENTS. A PROSPECTIVE RANDOMIZED STUDY
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Bouillanne, O., primary, Hamon-Vilcot, B., additional, Curis, E., additional, Nicolis, I., additional, Chretien, P., additional, Schauer, N., additional, Coulombel, I., additional, Vincent, J., additional, Cynober, L., additional, and Aussel, C., additional
- Published
- 2009
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17. Integrated genomics approaches using introgression lines of tomato
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Fernie, A., primary, Schauer, N., additional, Semel, Y., additional, Kochevenko, A., additional, Fait, A., additional, Carrari, F., additional, and Zamir, D., additional
- Published
- 2008
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18. Plant metabolomics: towards biological function and mechanism
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SCHAUER, N, primary and FERNIE, A, additional
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- 2006
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19. Full-Bit Functional, High-Density 8Mb 1T-1C FRAM Embedded Within a Low-Power 130nm Logic Process
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Udayakumar, K. R., primary, Moise, T. S., additional, Summerfelt, S. R., additional, Celii, F. G., additional, Shinn, G., additional, Boku, K., additional, Remack, K., additional, Haider, A., additional, Anderson, D., additional, Gertas, J., additional, Obeng, Y., additional, Albrecht, G., additional, Martin, J. S., additional, Rodriguez, J., additional, Khan, B., additional, Aggarwal, S., additional, Schauer, N., additional, McAdams, H., additional, Madan, S., additional, McKerrow, A., additional, Eliason, J., additional, Groat, J., additional, Bailey, R., additional, Fox, G. R, additional, Jabillo, E., additional, and Walbert, J., additional
- Published
- 2006
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20. Manufacture of high pressure die-cast radio frequency filter bodies
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Dargusch, M. S., primary, Wang, G., additional, Schauer, N., additional, Dinnis, C. M., additional, and Savage, G., additional
- Published
- 2005
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21. Metabolic profiling of leaves and fruit of wild species tomato: a survey of the Solanum lycopersicum complex
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Schauer, N., primary
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- 2004
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22. GMD@CSB.DB: the Golm Metabolome Database
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Kopka, J., primary, Schauer, N., additional, Krueger, S., additional, Birkemeyer, C., additional, Usadel, B., additional, Bergmuller, E., additional, Dormann, P., additional, Weckwerth, W., additional, Gibon, Y., additional, Stitt, M., additional, Willmitzer, L., additional, Fernie, A. R., additional, and Steinhauser, D., additional
- Published
- 2004
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23. Clinical Presentation of Rupture of the Left-Ventricular Free Wall After Myocardial Infarction: Report of Five Cases with Successful Surgical Repair
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Schwarz, C., primary, Punzengruber, C., additional, Ng, C., additional, Schauer, N., additional, Hartl, P., additional, and Pachinger, O., additional
- Published
- 1996
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24. Metabolism of Formate in Methanobacterium formicicum
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Schauer, N. L. and Ferry, J. G.
- Abstract
Methanobacterium formicicumstrain JF-1 was cultured with formate as the sole energy source in a pH-stat fermentor. Growth was exponential, and both methane production and formate consumption were linear functions of the growth rate. Hydrogen was produced in only trace amounts, and the dissolved H2concentration of the culture medium was below 1 μM. The effect of temperature or pH on the rate of methane formation was studied with a single fermentor culture in mid-log phase that was grown with formate under standard conditions at 37°C and pH 7.6. Methane formation from formate occurred over the pH range from 6.5 to 8.6, with a maximum at pH 8.0. The maximum temperature of methanogenesis was 56°C. H2production increased at higher temperatures. Hydrogen and formate were consumed throughout growth when both were present in saturating concentrations. The molar growth yields were 1.2 ± 0.06 g (dry weight) per mol of formate and 4.8 ± 0.24 g (dry weight) per mol of methane. Characteristics were compared for cultures grown with either formate or H2-CO2as the sole energy source at 37°C and pH 7.6; the molar growth yield for methane of formate cultures was 4.8 g (dry weight) per mol, and that of H2-CO2cultures was 3.5 g (dry weight) per mol. Both formate and H2-CO2cultures had low efficiencies of electron transport phosphorylation; formate-cultured cells had greater specific activities of coenzyme F420than did H2-CO2-grown cultures. Hydrogenase, formate dehydrogenase, chromophoric factor F342, and low levels of formyltetrahydrofolate synthetase were present in cells cultured with either substrate. Methyl viologen-dependent formate dehydrogenase was found in the soluble fraction from broken cells.
- Published
- 1980
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25. FAD requirement for the reduction of coenzyme F420 by formate dehydrogenase from Methanobacterium formicicum
- Author
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Schauer, N L and Ferry, J G
- Abstract
The partial purification of the formate dehydrogenase from cell-free extracts of Methanobacterium formicicum decreased the rate of coenzyme F420 reduction 175-fold relative to the rate of methyl viologen reduction. FAD, isolated from this organism, reactivated the coenzyme F420-dependent activity of purified formate dehydrogenase and restored the activity ratio (coenzyme F420/methyl viologen) to near that in cell-free extracts. Neither flavin mononucleotide nor FADH2 replaced FAD. The reduced form of FAD inhibited the reactivation of coenzyme F420-dependent formate dehydrogenase activity by the oxidized form. The results suggest that native formate dehydrogenase from Methanobacterium formicicum contains noncovalently bound FAD that is required for coenzyme F420-dependent activity.
- Published
- 1983
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26. Properties of formate dehydrogenase in Methanobacterium formicicum
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Schauer, N L and Ferry, J G
- Abstract
Soluble formate dehydrogenase from Methanobacterium formicicum was purified 71-fold with a yield of 35%. Purification was performed anaerobically in the presence of 10 mM sodium azide which stabilized the enzyme. The purified enzyme reduced, with formate, 50 mumol of methyl viologen per min per mg of protein and 8.2 mumol of coenzyme F420 per min per mg of protein. The apparent Km for 7,8-didemethyl-8-hydroxy-5-deazariboflavin, a hydrolytic derivative of coenzyme F420, was 10-fold greater (63 microM) than for coenzyme F420 (6 microM). The purified enzyme also reduced flavin mononucleotide (Km = 13 microM) and flavin adenine dinucleotide (Km = 25 microM) with formate, but did not reduce NAD+ or NADP+. The reduction of NADP+ with formate required formate dehydrogenase, coenzyme F420, and coenzyme F420:NADP+ oxidoreductase. The formate dehydrogenase had an optimal pH of 7.9 when assayed with the physiological electron acceptor coenzyme F420. The optimal reaction rate occurred at 55 degrees C. The molecular weight was 288,000 as determined by gel filtration. The purified formate dehydrogenase was strongly inhibited by cyanide (Ki = 6 microM), azide (Ki = 39 microM), alpha,alpha-dipyridyl, and 1,10-phenanthroline. Denaturation of the purified formate dehydrogenase with sodium dodecyl sulfate under aerobic conditions revealed a fluorescent compound. Maximal excitation occurred at 385 nm, with minor peaks at 277 and 302 nm. Maximal fluorescence emission occurred at 455 nm.
- Published
- 1982
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27. Cloning, expression, and nucleotide sequence of the formate dehydrogenase genes from Methanobacterium formicicum.
- Author
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Shuber, A P, Orr, E C, Recny, M A, Schendel, P F, May, H D, Schauer, N L, and Ferry, J G
- Abstract
The genes for the two subunits of the formate dehydrogenase from Methanobacterium formicicum were cloned and their sequences determined. When expressed in Escherichia coli, two proteins were produced which had the appropriate mobility on an SDS gel for the two subunits of formate dehydrogenase and cross-reacted with antibodies raised to purified formate dehydrogenase. The genes for the two formate dehydrogenase subunits overlap by 1 base pair and are preceded by DNA sequences similar to both eubacterial and archaebacterial promoters and ribosome-binding sites. The amino acid sequences deduced from the DNA sequence were analyzed, and the arrangement of putative iron-sulfur centers is discussed.
- Published
- 1986
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28. Formate dehydrogenase from Methanobacterium formicicum. Electron paramagnetic resonance spectroscopy of the molybdenum and iron-sulfur centers.
- Author
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Barber, M J, Siegel, L M, Schauer, N L, May, H D, and Ferry, J G
- Abstract
Formate dehydrogenase from Methanobacterium formicicum was examined by electron paramagnetic resonance spectroscopy. Although oxidized enzyme yielded no EPR signals over the temperature range 8-200 K, dithionite reduction resulted in generation of two paramagnetic components. The first, a nearly isotropic signal visible at temperatures below 200 K with g1 = 2.018, g2 = 2.003, and g3 = 1.994, exhibited nuclear hyperfine interaction with two equivalent protons (A1 = 0.45, A2 = 0.6, and A3 = 0.55 milliTeslas). EPR spectra of partially reduced 95Mo-enriched formate dehydrogenase exhibited additional 3-4 milliTeslas splittings, due to spin interaction with the 95Mo nucleus. Thus, this signal is due to a Mo center. This is the first reported example of a Mo center with gav greater than 2.0 in a biological system. The second species, a rhombic signal visible below 40 K with g values of g1 = 2.0465, g2 = 1.9482, and g3 = 1.9111 showed no hyperfine coupling and was assigned to reduced Fe/S. Both paramagnetic species could be detected in samples of M. formicicum whole cells anaerobically reduced with sodium formate. The Mo(V) signal was altered following addition of cyanide (g1 = 1.996, g2 = 1.988, and g3 = 1.980). Growth of bacteria in the presence of 1 mM WO4(2-) resulted in abolition of the Mo(V) EPR signal and formate dehydrogenase activity. Em, 7.7 was -330 mV for Mo(VI)/Mo(V) and -470 mV for Mo(V)/Mo(IV).
- Published
- 1983
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29. Molybdopterin cofactor from Methanobacterium formicicum formate dehydrogenase
- Author
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May, H D, Schauer, N L, and Ferry, J G
- Abstract
The molybdopterin cofactor from the formate dehydrogenase of Methanobacterium formicicum was studied. The cofactor was released by guanidine denaturation of homogeneous enzyme, which also released greater than 80% of the molybdenum present in the enzyme. The anoxically isolated cofactor was nonfluorescent, but after exposure to air it fluoresced with spectra similar to those of described molybdopterin cofactors. Aerobic release from acid-denatured formate dehydrogenase in the presence of I2 and potassium iodide produced a mixture of fluorescent products. Alkaline permanganate oxidation of the mixture yielded pterin-6-carboxylic acid as the only detectable fluorescent product. The results showed that the cofactor from formate dehydrogenase contained a pterin nucleus with a 6-alkyl side chain of unknown structure. Covalently bound phosphate was also present. The isolated cofactor was unable to complement the cofactor-deficient nitrate reductase of the Neurospora crassa nit-1 mutant.
- Published
- 1986
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30. Composition of the coenzyme F420-dependent formate dehydrogenase from Methanobacterium formicicum
- Author
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Schauer, N L and Ferry, J G
- Abstract
The coenzyme F420-dependent formate dehydrogenase from Methanobacterium formicicum was purified to electrophoretic homogeneity by anoxic procedures which included the addition of azide, flavin adenine dinucleotide (FAD), glycerol, and 2-mercaptoethanol to all buffer solutions to stabilize activity. The enzyme contains, in approximate molar ratios, 1 FAD molecule and 1 molybdenum, 2 zinc, 21 to 24 iron, and 25 to 29 inorganic sulfur atoms. Denaturation of the enzyme released a molybdopterin cofactor. The enzyme has a molecular weight of 177,000 and consists of one each of two different subunits, giving the composition alpha 1 beta 1. The molecular weight of the alpha-subunit is 85,000, and that of the beta-subunit is 53,000. The UV-visible spectrum is typical of nonheme iron-sulfur flavoprotein. Reduction of the enzyme facilitated dissociation of FAD, and the FAD-depleted enzyme was unable to reduce coenzyme F420. Preincubation of the FAD-depleted enzyme with FAD restored coenzyme F420-dependent activity.
- Published
- 1986
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31. Expression of EAAT1 reflects a possible neuroprotective function of reactive astrocytes and activated microglia following human traumatic brain injury
- Author
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Beschorner, R., Dietz, K., Schauer, N., Mittelbronn, M., Schluesener, H. J., Trautmann, K., Meyermann, R., and Perikles Simon
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Adult ,Aged, 80 and over ,Male ,Time Factors ,Adolescent ,Brain ,Middle Aged ,Immunohistochemistry ,Neuroprotection ,Excitatory Amino Acid Transporter 1 ,Glutamate Plasma Membrane Transport Proteins ,Excitatory Amino Acid Transporter 2 ,Astrocytes ,Brain Injuries ,Case-Control Studies ,Humans ,Female ,Microglial activation ,Microglia ,Aged ,61 - Medicina - Abstract
Glutamate-mediated excitotoxicity is known to cause secondary brain damage following stroke and traumatic brain injury (TBI). However, clinical trials using NMDA antagonists failed. Thus, glial excitatory amino acid transporters (EAATs) might be a promising target for therapeutic intervention. Methods and Results. We examined expression of EAAT1 (GLAST) and EAAT2 (Glt-1) in 36 TBI cases by immunohistochemistry. Cortical expression of both EAATs decreased rapidly and widespread throughout the brain (in lesional, adjacent and remote areas) following TBI. In the white matter numbers of EAAT1+ parenchymal cells increased 39-fold within 24h (p
32. Metabolism of Formate inMethanobacterium formicicum
- Author
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Schauer, N. L., primary and Ferry, J. G., additional
- Published
- 1980
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33. A MODIFIED BLOW-GUN SYRINGE FOR REMOTE INJECTION OF CAPTIVE WILDLIFE
- Author
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WARREN, R. J., primary, SCHAUER, N. L., additional, JONES, J. T., additional, SCANLON, P. F., additional, and KIRKPATRICK, R. L., additional
- Published
- 1979
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34. Lead Levels in Primary Feathers of American Woodcocks Harvested by Hunters Throughout the United States Range
- Author
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O'Brien, T. G., Scanlon, P. F., Oderwald, R. G., and Schauer, N. L.
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LEAD ,RANGELANDS ,AMERICAN woodcock - Published
- 1979
35. Heavy Metal Levels in Feathers of Wild Turkeys From Virginia
- Author
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O'Brien, T. G., Schauer, N. L., Coggin, J. L., Scanlon, P. F., and Steffen, D. E.
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HEAVY metals - Published
- 1979
36. Manipulation of β-carotene levels in tomato fruits results in increased ABA content and extended shelf-life
- Author
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Jocelyn K. C. Rose, Claudia Fabbri, Benedetta Mattei, Sarah Frusciante, Alisdair R. Fernie, Antonio J. Matas, Reinhard Jetter, Nicolas Schauer, Giovanni Giuliano, James J. Giovannoni, Lucas Busta, Alessia Fiore, Gianfranco Diretto, Zhonghua Wang, Diretto, G., Frusciante, S., Fabbri, C., Schauer, N., Busta, L., Wang, Z., Matas, A. J., Fiore, A., K. C. Rose, J., Fernie, A. R., Jetter, R., Mattei, B., Giovannoni, J., and Giuliano, G.
- Subjects
0106 biological sciences ,0301 basic medicine ,Ethylene ,medicine.medical_treatment ,Plant Science ,Cutin ,Biology ,tomato ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,Solanum lycopersicum ,Gene Expression Regulation, Plant ,β-carotene ,medicine ,β‐carotene ,Food science ,Carotenoid ,Abscisic acid ,Research Articles ,Plant Proteins ,2. Zero hunger ,chemistry.chemical_classification ,tomato, β-carotene, ABA, ripening ,Phenylpropanoid ,Carotene ,fungi ,food and beverages ,Ripening ,beta Carotene ,Lycopene ,ripening ,030104 developmental biology ,chemistry ,ABA ,Fruit ,Agronomy and Crop Science ,010606 plant biology & botany ,Biotechnology ,Abscisic Acid ,Research Article - Abstract
Tomato fruit ripening is controlled by the hormone ethylene and by a group of transcription factors, acting upstream of ethylene. During ripening, the linear carotene lycopene accumulates at the expense of cyclic carotenoids. Fruit-specific overexpression of LYCOPENE β-CYCLASE (LCYb) resulted in increased β-carotene (provitamin A) content. Unexpectedly, LCYb-overexpressing fruits also exhibited a diverse array of ripening phenotypes, including delayed softening and extended shelf life. These phenotypes were accompanied, at the biochemical level, by an increase of abscisic acid (ABA) content, decreased ethylene production, increased density of cell wall material containing linear pectins with a low degree of methylation, and a thicker cuticle with a higher content of cutin monomers and triterpenoids. The levels of several primary metabolites and phenylpropanoid compounds were also altered in the transgenic fruits, which could be attributed to delayed fruit ripening and/or to ABA. Network correlation analysis and pharmacological experiments with the ABA biosynthesis inhibitor, abamine, indicated that altered ABA levels were a direct effect of the increased β-carotene content and were in turn responsible for the extended shelf life phenotype. Thus, manipulation of β-carotene levels results not only in an improvement of the nutritional value of tomato fruits, but also of their shelf life.
- Published
- 2020
37. VEGF-C-expressing TAMs rewire the metastatic fate of breast cancer cells.
- Author
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Banerjee K, Kerzel T, Bekkhus T, de Souza Ferreira S, Wallmann T, Wallerius M, Landwehr LS, Agardy DA, Schauer N, Malmerfeldt A, Bergh J, Bartish M, Hartman J, Östman A, Squadrito ML, and Rolny C
- Subjects
- Humans, Female, Lymphatic Metastasis, Tumor-Associated Macrophages metabolism, Vascular Endothelial Growth Factor C metabolism, Lymphangiogenesis, Tumor Microenvironment, Breast Neoplasms pathology
- Abstract
The expression of pro-lymphangiogenic VEGF-C in primary tumors is associated with sentinel lymph node metastasis in most solid cancer types. However, the impact of VEGF-C on distant organ metastasis remains unclear. Perivascular tumor-associated macrophages (TAMs) play a crucial role in guiding hematogenous spread of cancer cells by establishing metastatic pathways within the tumor microenvironment. This process supports breast cancer cell intravasation and metastatic dissemination. We show here that VEGF-C-expressing TAMs reduce the dissemination of mammary cancer cells to the lungs while concurrently increasing lymph node metastasis. These TAMs express podoplanin and interact with normalized tumor blood vessels expressing VEGFR3. Moreover, clinical data suggest inverse association between VEGF-C-expressing TAMs and breast cancer malignancy. Thus, our study elucidates the paradoxical role of VEGF-C-expressing TAMs in redirecting cancer cells to preferentially disseminate to lymph nodes rather than to lungs, partially achieved by normalizing tumor blood vessels and promoting lymphangiogenesis., Competing Interests: Declaration of interests J.H. has obtained speaker’s honoraria or advisory board remunerations from Roche, Novartis, Pfizer, EliLilly, MSD, Seagen, and AstraZeneca and has received institutional research support from Cepheid, Roche, AstraZeneca, and Novartis. J.H. is a co-founder and shareholder of Stratipath AB. A.Ö. is co-founder of TECKNET AB and has in recent years received research support from IPSEN AB. J.B. has research grants from Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche, and Sanofi-Aventis to Karolinska Institutet and/or University Hospital. No personal payments. Co-author on a chapter on "Prognostic and Predictive factors in early, non-metastatic breast cancer" in UpToDate. Honoraria to Asklepios Medicin HB. Stocks in Stratipath AB, a company involved in AI-based diagnostics for breast cancer. Chairperson for Coronis and Asklepios Cancer Research HB. Honoraria from Roche and AstraZeneca for chairmanship and lectures at scientific meetings and consultations for Stratipath AB., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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38. Matrix Metalloproteases and Cathepsin D in Human Serum do not Cleave Prolactin to Generate Vasoinhibin.
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Triebel J, Schauer N, Zamora M, Moreno-Vega AI, Escalera GM, Clapp C, and Bertsch T
- Subjects
- Adult, Aged, 80 and over, Cathepsin D blood, Cell Cycle Proteins blood, Diabetes Mellitus, Type 2 metabolism, Female, Humans, Male, Matrix Metalloproteinases blood, Middle Aged, Prolactin blood, Proteolysis, Cathepsin D metabolism, Cell Cycle Proteins metabolism, Matrix Metalloproteinases metabolism, Prolactin metabolism
- Abstract
Background: Vasoinhibin is generated in the pituitary gland and in multiple target tissues by proteolytic cleavage of prolactin by matrix metalloproteinases and cathepsin D. A dysregulation of vasoinhibin generation appears to contribute to diabetic retinopathy and diabetic macular edema, retinopathy of prematurity, peripartum cardiomyopathy, and preeclampsia. Here, we investigate whether vasoinhibin is generated by matrix metalloproteinases and cathepsin D in human serum., Methods: The abundance of matrix metalloproteinases 1, 2, 3, 8, 9, 10, 13, tissue inhibitors of metalloproteinases 1, 2, 4, and the activity of cathepsin D in serum samples were determined. Samples from healthy male (n = 3) and female (n = 2) subjects, pregnant subjects (n = 2), and patients with type 2 diabetes mellitus (n = 2) were investigated. The samples were incubated with recombinant prolactin at 37°C, under different pH, time, and buffer conditions. Prolactin and cleaved prolactin products were investigated by SDS-PAGE and western blotting., Results: Matrix metalloproteases-1, -2, -3, -8, -9, -10, -13, TIMP-1, -2, and -4, and the activity of cathepsin D were detected in all sera. Full-length prolactin incubated with human sera, containing endogenous matrix metalloproteinases and cathepsin D, remained intact at neutral pH during a time frame from 1 to 24 hours. Partial enzymatic cleavage of prolactin resulting in the generation of a vasoinhibin-like 17 kDa peptide was observed in samples incubated at pH 3.4. Heat inactivation of the serum and the addition of an MMP inhibitor suppressed the generation of the 17 kDa peptide, indicating that its generation was MMP-mediated., Conclusions: Vasoinhibin generation by enzymatic cleavage of prolactin by matrix metalloproteases or cathepsin D does not occur in human serum at physiological pH. A limited proteolysis of prolactin, resulting in the generation of a vasoinhibin-like peptide with an apparent molecular weight of 17 kDa occurs in serum at acidic pH. The generation of vasoinhibin may require the cellular and tissue microenvironments.
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- 2020
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39. Manipulation of β-carotene levels in tomato fruits results in increased ABA content and extended shelf life.
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Diretto G, Frusciante S, Fabbri C, Schauer N, Busta L, Wang Z, Matas AJ, Fiore A, K C Rose J, Fernie AR, Jetter R, Mattei B, Giovannoni J, and Giuliano G
- Subjects
- Abscisic Acid, Fruit metabolism, Gene Expression Regulation, Plant, Plant Proteins genetics, Plant Proteins metabolism, beta Carotene, Solanum lycopersicum genetics, Solanum lycopersicum metabolism
- Abstract
Tomato fruit ripening is controlled by the hormone ethylene and by a group of transcription factors, acting upstream of ethylene. During ripening, the linear carotene lycopene accumulates at the expense of cyclic carotenoids. Fruit-specific overexpression of LYCOPENE β-CYCLASE (LCYb) resulted in increased β-carotene (provitamin A) content. Unexpectedly, LCYb-overexpressing fruits also exhibited a diverse array of ripening phenotypes, including delayed softening and extended shelf life. These phenotypes were accompanied, at the biochemical level, by an increase in abscisic acid (ABA) content, decreased ethylene production, increased density of cell wall material containing linear pectins with a low degree of methylation, and a thicker cuticle with a higher content of cutin monomers and triterpenoids. The levels of several primary metabolites and phenylpropanoid compounds were also altered in the transgenic fruits, which could be attributed to delayed fruit ripening and/or to ABA. Network correlation analysis and pharmacological experiments with the ABA biosynthesis inhibitor, abamine, indicated that altered ABA levels were a direct effect of the increased β-carotene content and were in turn responsible for the extended shelf life phenotype. Thus, manipulation of β-carotene levels results in an improvement not only of the nutritional value of tomato fruits, but also of their shelf life., (© 2019 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)
- Published
- 2020
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40. Involvement of Lactate and Pyruvate in the Anti-Inflammatory Effects Exerted by Voluntary Activation of the Sympathetic Nervous System.
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Zwaag J, Ter Horst R, Blaženović I, Stoessel D, Ratter J, Worseck JM, Schauer N, Stienstra R, Netea MG, Jahn D, Pickkers P, and Kox M
- Abstract
We recently demonstrated that the sympathetic nervous system can be voluntarily activated following a training program consisting of cold exposure, breathing exercises, and meditation. This resulted in profound attenuation of the systemic inflammatory response elicited by lipopolysaccharide (LPS) administration. Herein, we assessed whether this training program affects the plasma metabolome and if these changes are linked to the immunomodulatory effects observed. A total of 224 metabolites were identified in plasma obtained from 24 healthy male volunteers at six timepoints, of which 98 were significantly altered following LPS administration. Effects of the training program were most prominent shortly after initiation of the acquired breathing exercises but prior to LPS administration, and point towards increased activation of the Cori cycle. Elevated concentrations of lactate and pyruvate in trained individuals correlated with enhanced levels of anti-inflammatory interleukin (IL)-10. In vitro validation experiments revealed that co-incubation with lactate and pyruvate enhances IL-10 production and attenuates the release of pro-inflammatory IL-1β and IL-6 by LPS-stimulated leukocytes. Our results demonstrate that practicing the breathing exercises acquired during the training program results in increased activity of the Cori cycle. Furthermore, this work uncovers an important role of lactate and pyruvate in the anti-inflammatory phenotype observed in trained subjects.
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- 2020
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41. Metabolic profiling of wheat rachis node infection by Fusarium graminearum - decoding deoxynivalenol-dependent susceptibility.
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Bönnighausen J, Schauer N, Schäfer W, and Bormann J
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- Amino Acids metabolism, Cell Wall metabolism, Fusarium genetics, Fusarium metabolism, Host-Pathogen Interactions physiology, Metabolome, Mutation, Mycotoxins metabolism, Reactive Oxygen Species metabolism, Sugar Alcohols metabolism, gamma-Aminobutyric Acid metabolism, Fusarium pathogenicity, Plant Diseases microbiology, Trichothecenes metabolism, Triticum metabolism, Triticum microbiology
- Abstract
Fusarium graminearum is a filamentous ascomycete and the causal agent of Fusarium head blight on wheat that threatens food and feed production worldwide as infection reduces crop yield both quantitatively by interfering with kernel development and qualitatively by poisoning any remaining kernels with mycotoxins. In wheat, F. graminearum infects spikelets and colonizes the entire head by growing through the rachis node at the bottom of each spikelet. Without the mycotoxin deoxynivalenol (DON), the pathogen cannot penetrate the rachis node and wheat is able to resist colonization. Using a global metabolite profiling approach we compared the metabolic profile of rachis nodes inoculated with either water, the Fusarium graminearum wild-type or the DON-deficient ∆tri5 mutant. Extensive metabolic rearrangements mainly affect metabolites for general stress perception and signaling, reactive oxygen species (ROS) metabolism, cell wall composition, the tri-carbonic acid (TCA) cycle and γ-aminobutyric acid (GABA) shunt as well as sugar alcohols, amino acids, and storage carbohydrates. The results revealed specific, DON-related susceptibility factors. Wild-type infection resulted in an oxidative burst and the induction of plant programmed cell death, while spread of the DON-deficient mutant was blocked in a jasmonate (JA)-related defense reaction in concert with other factors. Hence, the ∆tri5 mutant is prone to defense reactions that are, in the case of a wild-type infection, not initiated., (© 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.)
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- 2019
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42. Selective binding of matrix metalloproteases MMP-9 and MMP-12 to inhibitor-assisted thermolysin-imprinted beads.
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Schauer N, Dinc M, Raabe B, Hummel T, Müller M, Sobek H, and Mizaikoff B
- Abstract
Protein-imprinted polymers have been synthesized to recognize and specifically bind selected proteins. However, protein imprinting requires substantial amounts of pure protein to efficiently obtain imprinted polymers for large scale applications, e.g. protein purification by affinity chromatography. In the absence of large quantities of a pure protein of interest, an alternative strategy was developed. In this case study, neutral metalloprotease thermolysin was selected as a commercially available surrogate for imprinting polymer beads. Phosphoramidon-assisted thermolysin-imprinted beads were synthesized. During rebinding experiments, it was shown that these beads specifically bind to thermolysin. In addition, it was shown that these beads also bind in CHO cell culture supernatant to the matrix metalloprotease-9 and -12 (MMP-9, -12). Therefore, these beads can be applied as a selective sorbent for the rare metalloproteases MMP-9 and MMP-12 to remove these proteases from CHO cell culture supernatants. The high selectivity of thermolysin-imprinted beads can be extended to other proteases of the family of metalloproteases, and is not limited to thermolysin. This innovative approach is suitable to address the challenges in the field of protease purification and isolation from biotechnologically relevant media., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)
- Published
- 2018
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43. Metabolomic Profiles for Primary Progressive Multiple Sclerosis Stratification and Disease Course Monitoring.
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Stoessel D, Stellmann JP, Willing A, Behrens B, Rosenkranz SC, Hodecker SC, Stürner KH, Reinhardt S, Fleischer S, Deuschle C, Maetzler W, Berg D, Heesen C, Walther D, Schauer N, Friese MA, and Pless O
- Abstract
Primary progressive multiple sclerosis (PPMS) shows a highly variable disease progression with poor prognosis and a characteristic accumulation of disabilities in patients. These hallmarks of PPMS make it difficult to diagnose and currently impossible to efficiently treat. This study aimed to identify plasma metabolite profiles that allow diagnosis of PPMS and its differentiation from the relapsing-remitting subtype (RRMS), primary neurodegenerative disease (Parkinson's disease, PD), and healthy controls (HCs) and that significantly change during the disease course and could serve as surrogate markers of multiple sclerosis (MS)-associated neurodegeneration over time. We applied untargeted high-resolution metabolomics to plasma samples to identify PPMS-specific signatures, validated our findings in independent sex- and age-matched PPMS and HC cohorts and built discriminatory models by partial least square discriminant analysis (PLS-DA). This signature was compared to sex- and age-matched RRMS patients, to patients with PD and HC. Finally, we investigated these metabolites in a longitudinal cohort of PPMS patients over a 24-month period. PLS-DA yielded predictive models for classification along with a set of 20 PPMS-specific informative metabolite markers. These metabolites suggest disease-specific alterations in glycerophospholipid and linoleic acid pathways. Notably, the glycerophospholipid LysoPC(20:0) significantly decreased during the observation period. These findings show potential for diagnosis and disease course monitoring, and might serve as biomarkers to assess treatment efficacy in future clinical trials for neuroprotective MS therapies.
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- 2018
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44. Promising Metabolite Profiles in the Plasma and CSF of Early Clinical Parkinson's Disease.
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Stoessel D, Schulte C, Teixeira Dos Santos MC, Scheller D, Rebollo-Mesa I, Deuschle C, Walther D, Schauer N, Berg D, Nogueira da Costa A, and Maetzler W
- Abstract
Parkinson's disease (PD) shows high heterogeneity with regard to the underlying molecular pathogenesis involving multiple pathways and mechanisms. Diagnosis is still challenging and rests entirely on clinical features. Thus, there is an urgent need for robust diagnostic biofluid markers. Untargeted metabolomics allows establishing low-molecular compound biomarkers in a wide range of complex diseases by the measurement of various molecular classes in biofluids such as blood plasma, serum, and cerebrospinal fluid (CSF). Here, we applied untargeted high-resolution mass spectrometry to determine plasma and CSF metabolite profiles. We semiquantitatively determined small-molecule levels (≤1.5 kDa) in the plasma and CSF from early PD patients (disease duration 0-4 years; n = 80 and 40, respectively), and sex- and age-matched controls ( n = 76 and 38, respectively). We performed statistical analyses utilizing partial least square and random forest analysis with a 70/30 training and testing split approach, leading to the identification of 20 promising plasma and 14 CSF metabolites. These metabolites differentiated the test set with an AUC of 0.8 (plasma) and 0.9 (CSF). Characteristics of the metabolites indicate perturbations in the glycerophospholipid, sphingolipid, and amino acid metabolism in PD, which underscores the high power of metabolomic approaches. Further studies will enable to develop a potential metabolite-based biomarker panel specific for PD.
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- 2018
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45. Metabolomic profile and nucleoside composition of Cordyceps nidus sp. nov. (Cordycipitaceae): A new source of active compounds.
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Chiriví J, Danies G, Sierra R, Schauer N, Trenkamp S, Restrepo S, and Sanjuan T
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- Asia, Cordyceps growth & development, Anti-Bacterial Agents pharmacology, Antioxidants pharmacology, Cordyceps metabolism, Gram-Positive Bacteria drug effects, Metabolomics, Nucleosides metabolism
- Abstract
Cordyceps sensu lato is a genus of arthropod-pathogenic fungi, which have been used traditionally as medicinal in Asia. Within the genus, Ophiocordyceps sinensis is the most coveted and expensive species in China. Nevertheless, harvesting wild specimens has become a challenge given that natural populations of the fungus are decreasing and because large-scale culture of it has not yet been achieved. The worldwide demand for products derived from cultivable fungal species with medicinal properties has increased recently. In this study, we propose a new species, Cordyceps nidus, which parasitizes underground nests of trapdoor spiders. This species is phylogenetically related to Cordyceps militaris, Cordyceps pruinosa, and a sibling species of Cordyceps caloceroides. It is found in tropical rainforests from Bolivia, Brazil, Colombia and Ecuador. We also investigated the medicinal potential of this fungus based on its biochemical properties when grown on four different culture media. The metabolic profile particularly that of nucleosides, in polar and non-polar extracts was determined by UPLC, and then correlated to their antimicrobial activity and total phenolic content. The metabolome showed a high and significant dependency on the substrate used for fungal growth. The mass intensities of nucleosides and derivative compounds were higher in natural culture media in comparison to artificial culture media. Among these compounds, cordycepin was the predominant, showing the potential use of this species as an alternative to O. sinensis. Furthermore, methanol fractions showed antimicrobial activity against gram-positive bacteria, and less than 3.00 mg of gallic acid equivalents per g of dried extract were obtained when assessing its total phenolic content by modified Folin-Ciocalteu method. The presence of polyphenols opens the possibility of further exploring the antioxidant capacity and the conditions that may enhance this characteristic. The metabolic composition and biochemical activity indicate potential use of C. nidus in pharmaceutical applications.
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- 2017
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46. Comprehensive comparison of in silico MS/MS fragmentation tools of the CASMI contest: database boosting is needed to achieve 93% accuracy.
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Blaženović I, Kind T, Torbašinović H, Obrenović S, Mehta SS, Tsugawa H, Wermuth T, Schauer N, Jahn M, Biedendieck R, Jahn D, and Fiehn O
- Abstract
In mass spectrometry-based untargeted metabolomics, rarely more than 30% of the compounds are identified. Without the true identity of these molecules it is impossible to draw conclusions about the biological mechanisms, pathway relationships and provenance of compounds. The only way at present to address this discrepancy is to use in silico fragmentation software to identify unknown compounds by comparing and ranking theoretical MS/MS fragmentations from target structures to experimental tandem mass spectra (MS/MS). We compared the performance of four publicly available in silico fragmentation algorithms (MetFragCL, CFM-ID, MAGMa+ and MS-FINDER) that participated in the 2016 CASMI challenge. We found that optimizing the use of metadata, weighting factors and the manner of combining different tools eventually defined the ultimate outcomes of each method. We comprehensively analysed how outcomes of different tools could be combined and reached a final success rate of 93% for the training data, and 87% for the challenge data, using a combination of MAGMa+, CFM-ID and compound importance information along with MS/MS matching. Matching MS/MS spectra against the MS/MS libraries without using any in silico tool yielded 60% correct hits, showing that the use of in silico methods is still important.
- Published
- 2017
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47. Synergistic Action of Genistein and Calcitriol in Immature Osteosarcoma MG-63 Cells by SGPL1 Up-Regulation.
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Engel N, Adamus A, Schauer N, Kühn J, Nebe B, Seitz G, and Kraft K
- Subjects
- Aldehyde-Lyases genetics, Animals, Cell Line, Tumor, Cell Proliferation drug effects, Drug Synergism, Estrogen Receptor beta genetics, Ethanolamine metabolism, Gene Expression Regulation, Neoplastic drug effects, Humans, Lysophospholipids metabolism, Mice, Osteoblasts drug effects, Osteoblasts metabolism, Osteosarcoma metabolism, Osteosarcoma pathology, Phytoestrogens administration & dosage, Receptors, Calcitriol genetics, Sphingosine analogs & derivatives, Sphingosine metabolism, Aldehyde-Lyases biosynthesis, Calcitriol administration & dosage, Estrogen Receptor beta biosynthesis, Genistein administration & dosage, Osteosarcoma drug therapy, Receptors, Calcitriol biosynthesis
- Abstract
Background: Phytoestrogens such as genistein, the most prominent isoflavone from soy, show concentration-dependent anti-estrogenic or estrogenic effects. High genistein concentrations (>10 μM) also promote proliferation of bone cancer cells in vitro. On the other hand, the most active component of the vitamin D family, calcitriol, has been shown to be tumor protective in vitro and in vivo. The purpose of this study was to examine a putative synergism of genistein and calcitriol in two osteosarcoma cell lines MG-63 (early osteoblast), Saos-2 (mature osteoblast) and primary osteoblasts., Methods: Thus, an initial screening based on cell cycle phase alterations, estrogen (ER) and vitamin D receptor (VDR) expression, live cell metabolic monitoring, and metabolomics were performed., Results: Exposure to the combination of 100 μM genistein and 10 nM calcitriol reduced the number of proliferative cells to control levels, increased ERß and VDR expression, and reduced extracellular acidification (40%) as well as respiratory activity (70%), primarily in MG-63 cells. In order to identify the underlying cellular mechanisms in the MG-63 cell line, metabolic profiling via GC/MS technology was conducted. Combined treatment significantly influenced lipids and amino acids preferably, whereas metabolites of the energy metabolism were not altered. The comparative analysis of the log2-ratios revealed that after combined treatment only the metabolite ethanolamine was highly up-regulated. This is the result: a strong overexpression (350%) of the enzyme sphingosine-1-phosphate lyase (SGPL1), which irreversibly degrades sphingosine-1-phosphate (S1P), thereby, generating ethanolamine. S1P production and secretion is associated with an increased capability of migration and invasion of cancer cells., Conclusion: From these results can be concluded that the tumor promoting effect of high concentrations of genistein in immature osteosarcoma cells is reduced by the co-administration of calcitriol, primarily by the breakdown of S1P. It should be tested whether this anti-metastatic pathway can be stimulated by combined treatment also in metastatic xenograft mice models., Competing Interests: There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2017
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48. C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man.
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van de Beek MC, Dijkstra IM, van Lenthe H, Ofman R, Goldhaber-Pasillas D, Schauer N, Schackmann M, Engelen-Lee JY, Vaz FM, Kulik W, Wanders RJ, Engelen M, and Kemp S
- Subjects
- ATP Binding Cassette Transporter, Subfamily D, Member 1, Animals, Biomarkers metabolism, Brain metabolism, Carnitine metabolism, Early Diagnosis, Fatty Acid Elongases, Fatty Acids metabolism, Gene Knock-In Techniques, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Oligodendroglia metabolism, Spinal Cord metabolism, ATP-Binding Cassette Transporters genetics, Acetyltransferases genetics, Adrenoleukodystrophy diagnosis, Adrenoleukodystrophy pathology, Carnitine analogs & derivatives, Lysophosphatidylcholines metabolism
- Abstract
X-linked adrenoleukodystrophy (ALD), a progressive neurodegenerative disease, is caused by mutations in ABCD1 and characterized by very-long-chain fatty acids (VLCFA) accumulation. Virtually all males develop progressive myelopathy (AMN). A subset of patients, however, develops a fatal cerebral demyelinating disease (cerebral ALD). Hematopoietic stem cell transplantation is curative for cerebral ALD provided the procedure is performed in an early stage of the disease. Unfortunately, this narrow therapeutic window is often missed. Therefore, an increasing number of newborn screening programs are including ALD. To identify new biomarkers for ALD, we developed an Abcd1 knockout mouse with enhanced VLCFA synthesis either ubiquitous or restricted to oligodendrocytes. Biochemical analysis revealed VLCFA accumulation in different lipid classes and acylcarnitines. Both C26:0-lysoPC and C26:0-carnitine were highly elevated in brain, spinal cord, but also in bloodspots. We extended the analysis to patients and confirmed that C26:0-carnitine is also elevated in bloodspots from ALD patients. We anticipate that validation of C26:0-carnitine for the diagnosis of ALD in newborn bloodspots may lead to a faster inclusion of ALD in newborn screening programs in countries that already screen for other inborn errors of metabolism.
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- 2016
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49. Corrigendum: Gas chromatography mass spectrometry-based metabolite profiling in plants.
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Lisec J, Schauer N, Kopka J, Willmitzer L, and Fernie AR
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- 2015
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50. Temperament type specific metabolite profiles of the prefrontal cortex and serum in cattle.
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Brand B, Hadlich F, Brandt B, Schauer N, Graunke KL, Langbein J, Repsilber D, Ponsuksili S, and Schwerin M
- Subjects
- Animals, Cattle, Cluster Analysis, Computational Biology, Metabolome, Metabolomics methods, Prefrontal Cortex metabolism, Serum metabolism, Temperament
- Abstract
In the past decade the number of studies investigating temperament in farm animals has increased greatly because temperament has been shown not only to affect handling but also reproduction, health and economically important production traits. However, molecular pathways underlying temperament and molecular pathways linking temperament to production traits, health and reproduction have yet to be studied in full detail. Here we report the results of metabolite profiling of the prefrontal cortex and serum of cattle with distinct temperament types that were performed to further explore their molecular divergence in the response to the slaughter procedure and to identify new targets for further research of cattle temperament. By performing an untargeted comprehensive metabolite profiling, 627 and 1097 metabolite features comprising 235 and 328 metabolites could be detected in the prefrontal cortex and serum, respectively. In total, 54 prefrontal cortex and 51 serum metabolite features were indicated to have a high relevance in the classification of temperament types by a sparse partial least square discriminant analysis. A clear discrimination between fearful/neophobic-alert, interested-stressed, subdued/uninterested-calm and outgoing/neophilic-alert temperament types could be observed based on the abundance of the identified relevant prefrontal cortex and serum metabolites. Metabolites with high relevance in the classification of temperament types revealed that the main differences between temperament types in the response to the slaughter procedure were related to the abundance of glycerophospholipids, fatty acyls and sterol lipids. Differences in the abundance of metabolites related to C21 steroid metabolism and oxidative stress indicated that the differences in the metabolite profiles of the four extreme temperament types could be the result of a temperament type specific regulation of molecular pathways that are known to be involved in the stress and fear response.
- Published
- 2015
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