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71.
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Anke Gundula Roth Susanne Redmer Christoph Arenz Prof. Dr. 《Chembiochem : a European journal of chemical biology》2009,10(14):2367-2374
The different mammalian sphingomyelinases are involved in cell regulation, apoptosis and inflammatory events. Recent reports suggest pharmacological potential especially for inhibitors of the acid sphingomyelinase. Phosphatidyl inositol‐3,5bisphosphate (PtdIns3,5P2) is the most potent selective acid sphingomyelinase inhibitor known to date. In the present study, we synthesized analogues of PtdIns3,5P2 for initial structure–activity‐relationship (SAR) studies. We identified an inhibitor that is easy to synthesize, that has superior chemical and biophysical properties when compared to PtdIns3,5P2 and that should be stable against virtually all phospholipases. Last but not least, the new inhibitor partially protected cells from dexamethasone‐induced cell death. 相似文献
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Dr. Kornelia Hardes Dr. Gero L. Becker Dr. Yinghui Lu Dr. Sven O. Dahms Susanne Köhler Dr. Wolfgang Beyer Prof. Kirsten Sandvig Dr. Hiroyuki Yamamoto Prof. Iris Lindberg Lisa Walz Dr. Veronika von Messling Dr. Manuel E. Than Prof. Wolfgang Garten Prof. Torsten Steinmetzer 《ChemMedChem》2015,10(7):1218-1231
New peptidomimetic furin inhibitors with unnatural amino acid residues in the P3 position were synthesized. The most potent compound 4‐guanidinomethyl‐phenylacteyl‐Arg‐Tle‐Arg‐4‐amidinobenzylamide (MI‐1148) inhibits furin with a Ki value of 5.5 pM . The derivatives also strongly inhibit PC1/3, whereas PC2 is less affected. Selected inhibitors were tested in cell culture for antibacterial and antiviral activity against infectious agents known to be dependent on furin activity. A significant protective effect against anthrax and diphtheria toxin was observed in the presence of the furin inhibitors. Furthermore, the spread of the highly pathogenic H5N1 and H7N1 avian influenza viruses and propagation of canine distemper virus was strongly inhibited. Inhibitor MI‐1148 was crystallized in complex with human furin. Its N‐terminal guanidinomethyl group in the para position of the P5 phenyl ring occupies the same position as that found previously for a structurally related inhibitor containing this substitution in the meta position, thereby maintaining all of the important P5 interactions. Our results confirm that the inhibition of furin is a promising strategy for a short‐term treatment of acute infectious diseases. 相似文献
75.
Denise Loder Susanne Katharina Michelic Christian Bernhard 《BHM Berg- und Hüttenm?nnische Monatshefte》2016,161(7):315-320
The formation of acicular ferrite is mainly influenced by the steel composition, cooling rate, austenite grain size, and inclusion landscape. However, their precise effects have not been clarified in literature yet. Within the FWF project TRP 266-N19, a systematic methodology to study the influencing factors of the acicular ferrite formation as well as their interactions on laboratory scale was developed. The present work exemplarily demonstrates the application of this methodology for studying the effect of cooling rate and boron on the formation of acicular ferrite in a low-carbon HSLA steel. 相似文献
76.
Fibroblast Growth Factor 21 Response in a Preclinical Alcohol Model of Acute-on-Chronic Liver Injury
Grigorios Christidis Ersin Karatayli Rabea A. Hall Susanne N. Weber Matthias C. Reichert Mathias Hohl Sen Qiao Ulrich Boehm Dieter Lütjohann Frank Lammert Senem Ceren Karatayli 《International journal of molecular sciences》2021,22(15)
Background and Aims: Fibroblast growth factor (FGF) 21 has recently been shown to play a potential role in bile acid metabolism. We aimed to investigate the FGF21 response in an ethanol-induced acute-on-chronic liver injury (ACLI) model in Abcb4−/− mice with deficiency of the hepatobiliary phospholipid transporter. Methods: Total RNA was extracted from wild-type (WT, C57BL/6J) and Abcb4−/− (KO) mice, which were either fed a control diet (WT-Cont and KO-Cont groups; n = 28/group) or ethanol diet, followed by an acute ethanol binge (WT-EtOH and KO-EtOH groups; n = 28/group). A total of 58 human subjects were recruited into the study, including patients with alcohol-associated liver disease (AALD; n = 31) and healthy controls (n = 27). The hepatic and ileal expressions of genes involved in bile acid metabolism, plasma FGF levels, and bile acid and its precursors 7α- and 27-hydroxycholesterol (7α- and 27-OHC) concentrations were determined. Primary mouse hepatocytes were isolated for cell culture experiments. Results: Alcohol feeding significantly induced plasma FGF21 and decreased hepatic Cyp7a1 levels. Hepatic expression levels of Fibroblast growth factor receptor 1 (Fgfr1), Fgfr4, Farnesoid X-activated receptor (Fxr), and Small heterodimer partner (Shp) and plasma FGF15/FGF19 levels did not differ with alcohol challenge. Exogenous FGF21 treatment suppressed Cyp7a1 in a dose-dependent manner in vitro. AALD patients showed markedly higher FGF21 and lower 7α-OHC plasma levels while FGF19 did not differ. Conclusions: The simultaneous upregulation of FGF21 and downregulation of Cyp7a1 expressions upon chronic plus binge alcohol feeding together with the invariant plasma FGF15 and hepatic Shp and Fxr levels suggest the presence of a direct regulatory mechanism of FGF21 on bile acid homeostasis through inhibition of CYP7A1 by an FGF15-independent pathway in this ACLI model. Lay Summary: Alcohol challenge results in the upregulation of FGF21 and repression of Cyp7a1 expressions while circulating FGF15 and hepatic Shp and Fxr levels remain constant both in healthy and pre-injured livers, suggesting the presence of an alternative FGF15-independent regulatory mechanism of FGF21 on bile acid homeostasis through the inhibition of Cyp7a1. 相似文献
77.
Nitritation performance in membrane-aerated biofilm reactors differs from conventional biofilm systems 总被引:1,自引:0,他引:1
Susanne Lackner Akihiko Terada Harald Horn Mogens Henze Barth F. Smets 《Water research》2010,44(20):6073-6084
Nitrogen removal via nitrite has gained increasing attention in recent years due to its potential cost savings. Membrane-aerated biofilm reactors (MABRs) are one potential technology suitable to achieve nitritation. In this study we compared lab scale MABRs with conventional biofilm reactors to evaluate the influence of environmental conditions and operational parameters on nitritation performance. The oxygen mass transfer rate is postulated as a crucial parameter to control nitritation in the MABR: Clean water measurements showed significant underestimation of the total oxygen mass transfer, however, accurate determination of the oxygen mass transfer coefficient (km) of the system could be achieved by adjusting the liquid-phase mass transfer resistance in the constructed model. Batch experiments at different initial ammonium concentrations revealed that the conventional biofilm geometry was superior for nitritation compared to MABRs. These differences were reflected well in estimates of the oxygen affinity constants of the key microbial players, AOB and NOB (KO,AOB < KO,NOB (in both systems) and KO,NOB values smaller in the MABR vs. the conventional biofilm system). It also appeared that – in addition to oxygen limitation – the absolute and relative substrate concentrations in the biofilm (esp. of oxygen) are very important for successful nitritation. Initial biomass composition, furthermore, impacted reactor performance in the MABR systems indicating the need for appropriate inoculum choice. 相似文献
78.
Aiping Wu Eugene Baryschpolec Matthias Schaller Susanne Leppack 《Microelectronic Engineering》2010,87(9):1685-1688
Implementation of CoWP metal caps into Cu/low-k integration schemes requires a wet stripper that not only gives efficient cleaning but also has good compatibility to CoWP and low-k dielectrics. This paper describes a novel non-fluoride CoWP compatible stripper, developed based on a systematic study of the effect of stripper components, i.e. solvent, corrosion inhibitor, and stripper pH. Electrochemical methods were used to characterize galvanic corrosion of the CoWP/Cu couple and to estimate CoWP etch rate. Our studies showed that a traditional fluoride stripper caused severe damage to CoWP capping layer. The new stripper achieved a good balance between cleaning efficiency and compatibility to CoWP and low-k dielectrics, and demonstrated significant advantages in electrical properties over the traditional fluoride stripper. 相似文献
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