Christian Garve (1742–1798) zählte zu den prägenden Philosophen, Übersetzern und Publizisten der europäischen Aufklärung zwischen 1770 und 1800, und zwar sowohl innerhalb gewichtiger Teilbereiche der ...Fach- oder Schulphilosophie, wie der Moralphilosophie und Politik, als auch im Zusammenhang literarischer und populärphilosophischer Diskurse der sich entwickelnden und an Dynamik gewinnenden Öffentlichkeit. Garve nahm entscheidenden Einfluss auf wichtige Debatten, Kontroversen und Forschungsentwicklungen seiner Zeit; so entwickelte er Vorformen soziologischen Forschens und Argumentierens. Seine durch Friedrich II. angeregte Neuübersetzung und Kommentierung von Ciceros 'De officiis' war nicht nur ein großer Verkaufserfolg, sondern hatte auch immensen Einfluss auf die Debatten zur Moralphilosophie und deren pädagogische Umsetzung im späten 18. Jahrhundert – namentlich auf Kant.
Christian Garves Texte wurden im späten 18. Jahrhundert als heraustragende Beispiele für eine gelehrte und populäre Schreibweise bewundert. Zugleich genoss der Breslauer Aufklärer auch unter ...Fachkollegen aus der Philosophie und der Philologie große Reputation. Mit seinen Übersetzungen und Kommentaren englischer Autoren und lateinischer Klassiker beeinflusste er Generationen von Literaten und Philosophen. Der Band bietet erstmalig eine zwiesprachige Edition seiner frühen Dissertation zur Logik sowie seine ebenso berühmte wie umstrittene Studie zum Verhältnis von 'Moral und Politik'. Ergänzt wird diese Auswahl aus seinen monographischen Arbeiten durch kommentierte Editionen von Aufsätzen, dem Kommentar zur Fergussson-Übersetzung sowie repräsentative Rezensionen.
The genetic code is universal, but recombinant protein expression in heterologous systems is often hampered by divergent codon usage. Here, we demonstrate that reprogramming by standardized ...multi‐parameter gene optimization software and de novo gene synthesis is a suitable general strategy to improve heterologous protein expression. This study compares expression levels of 94 full‐length human wt and sequence‐optimized genes coding for pharmaceutically important proteins such as kinases and membrane proteins in E. coli. Fluorescence‐based quantification revealed increased protein yields for 70% of in vivo expressed optimized genes compared to the wt DNA sequences and also resulted in increased amounts of protein that can be purified. The improvement in transgene expression correlated with higher mRNA levels in our analyzed examples. In all cases tested, expression levels using wt genes in tRNA‐supplemented bacterial strains were outperformed by optimized genes expressed in non‐supplemented host cells.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Large-scale metabolic profiling is expected to develop into an integral part of functional genomics and systems biology. The metabolome of a cell or an organism is chemically highly complex. ...Therefore, comprehensive biochemical phenotyping requires a multitude of analytical techniques. Here, we describe a profiling approach that combines separation by capillary liquid chromatography with the high resolution, high sensitivity, and high mass accuracy of quadrupole time-of-flight mass spectrometry. About 2,000 different mass signals can be detected in extracts of Arabidopsis roots and leaves. Many of these originate from Arabidopsis secondary metabolites. Detection based on retention times and exact masses is robust and reproducible. The dynamic range is sufficient for the quantification of metabolites. Assessment of the reproducibility of the analysis showed that biological variability exceeds technical variability. Tools were optimized or established for the automatic data deconvolution and data processing. Subtle differences between samples can be detected as tested with the chalcone synthase deficient tt4 mutant. The accuracy of time-of-flight mass analysis allows to calculate elemental compositions and to tentatively identify metabolites. In-source fragmentation and tandem mass spectrometry can be used to gain structural information. This approach has the potential to significantly contribute to establishing the metabolome of Arabidopsis and other model systems. The principles of separation and mass analysis of this technique, together with its sensitivity and resolving power, greatly expand the range of metabolic profiling.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The properties of several cinnamic acid compounds used as matrices for matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were investigated as standard dried ...droplet (DD) and vacuum sublimed preparations. The differences between both preparation methods were analyzed with regard to matrix grain size, internal ion energy, initial velocity, analyte intensity, and analyte incorporation depth. Some of the used cinnamic acid derivatives exhibit clearly reduced grain sizes as sublimed preparations compared with standard DD approaches. In these cases higher effective temperatures could be measured accompanied by increased analyte intensities, which can be explained by stronger volatilization processes caused by a hindered heat dissipation resulting in a raised analyte transfer into the gas phase. For all sublimed compounds, a strong increase of the initial ion velocity compared with DD preparations could be measured. Higher initial ion velocities correlate with a decrease in internal ion energy which might be attributed to the very uniform crystal morphology exhibited by sublimed compounds. For sublimed matrices without reduced grain size, at least slightly higher analyte intensities could be detected at raised laser fluences. Analyte accumulation in the uppermost matrix layers or the detected higher ion stability can be explanations for these results.
The differences between standard dried droplet and vacuum sublimed surface preparations were analyzed for several cinnamic acid compounds used as matrices for MALDI-TOF MS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This is the first differential expression proteomics study on a human syngeneic cellular in vitro progression model of the colorectal adenoma-to-carcinoma sequence, the anchorage-dependent ...non-tumorigenic adenoma derived cell line AA/C1 and the derived anchorage-independent and tumorigenic carcinoma cell line AA/C1/SB10C. The study is based on quantitative 2-DE and is complemented by Western blot validation. Excluding redundancies due to proteolysis and post-translational modified isoforms of over 2000 protein spots, 13 proteins were revealed as regulated with statistical variance being within the 95th confidence level and were identified by peptide mass fingerprinting in MALDI MS. Progression-associated proteins belong to the functional complexes of anaerobic glycolysis/gluconeogenesis, steroid biosynthesis, prostaglandin biosynthesis, the regulation and maintenance of the cytoskeleton, protein biosynthesis and degradation, the regulation of apoptosis or other functions. Partial but significant overlap was revealed with previous proteomics and transcriptomics studies in colorectal carcinoma. Among upregulated proteins we identified 3-HMG-CoA synthase, protein phosphatase 1, prostaglandin E synthase 2, villin 1, annexin A1, triosephosphate isomerase, phosphoserine aminotransferase 1, fumarylacetoacetate hydrolase and pyrroline-5-carboxylate reductase 1 (PYCR1), while glucose-regulated protein 78, cathepsin D, lamin A/C and quinolate phosphoribosyltransferase were downregulated.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Levels of the peptide hormone hepcidin negatively correlate with systemic iron status and are increased in disorders in which iron metabolism is secondarily disregulated, such as the anemia of ...chronic disease. Consequently, the ability to measure hepcidin in the clinical setting may have diagnostic value for a broad range of indications. We describe a novel quantitative matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry assay for hepcidin in human urine which involves (i) direct enrichment from minute volumes (5 μL) of minimally treated urine on the surface of a functionalized chip, (ii) quantification by the use of a stable isotope labeled internal standard, and (iii) analysis by MALDI-TOF. Performance features include a wide linear range (1−1000 nM; LOQ 2.5 nM), high accuracy (90−110% recovery) and precision (intraday CV 12.11%; interday CV 13.21%), and a strong correlation upon interlaboratory cross validation with an existing immunoassay. The assay is simple, accurate, and efficient, and the high-throughput performance features of the assay make large-scale clinical research studies feasible.
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IJS, KILJ, NUK, PNG, UL, UM
Identification of mucin‐type O‐glycosylated proteins with known functions in model organisms like Drosophila could provide keys to elucidate functions of the O‐glycan moiety and proteomic analyses of ...O‐glycoproteins in higher eukaryotes remain a challenge due to structural heterogeneity and a lack of efficient tools for their specific isolation. Here we report a strategy to evaluate the O‐glycosylation potential of the embryonal hemocyte‐like Drosophila Schneider 2 (S2) cell line by expression of recombinant glycosylation probes derived from tandem repeats of the human mucin MUC1 or of the Drosophila salivary gland protein Sgs1. We obtained evidence that mucin‐type O‐glycosylation in S2 cells grown under serum‐free conditions is restricted to the Tn‐antigen (GalNAcα‐Ser/Thr) and the T‐antigen (Galβ1‐3GalNAcα‐Ser/Thr) and this structural homogeneity enables unique glycoproteomic strategies. We present a label‐free strategy for the isolation, profiling and analysis of O‐glycosylated proteins consisting of serial lectin affinity capture, 2‐DE‐based glycoprotein analysis by O‐glycan specific mAbs and protein identification by MALDI‐MS. Protein identity and O‐glycosylation was confirmed by ESI‐MS/MS with detection of diagnostic sugar oxonium‐ion fragments. Using this strategy, we established 2‐D reference maps and identified 21 secreted and intracellular mucin‐type O‐glycoproteins. Our results show that Drosophila S2 cells express O‐glycoproteins involved in a wide range of biological functions including proteins of the extracellular matrix (Laminin γ‐chain, Peroxidasin and Glutactin), pathogen recognition proteins (Gnbp1), stress response proteins (Glycoprotein 93), secreted proteases (Matrix‐metalloprotease 1 and various trypsin‐like serine proteases), protease inhibitors (Serpin 27A) and proteins of unknown function.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
9.
Kleine Schriften Roth, Udo; Stiening, Gideon
2021, Volume:
15.1
eBook
Das Werk von 1777 zählt zu den bedeutendsten Veröffentlichungen der Philosophie der Spätaufklärung. In insgesamt 14 umfangreichen Essays versucht Tetens die Grundprobleme der Aufklärungsphilosophie ...zu lösen. Der Band bietet die erste vollständige und kommentierte Ausgabe dieses opus magnum der empiristischen Spätaufklärung seit der Erstpublikation.
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