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Anne-Margarethe Enge Florian Kaltner Christoph Gottschalk Albert Braeuning Stefanie Hessel-Pras 《International journal of molecular sciences》2021,22(8)
1,2-unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites occurring as food contaminants that can cause severe liver damage upon metabolic activation in hepatocytes. However, it is yet unknown how these contaminants enter the cells. The role of hepatic transporters is only at the beginning of being recognized as a key determinant of PA toxicity. Therefore, this study concentrated on assessing the general mode of action of PA transport in the human hepatoma cell line HepaRG using seven structurally different PAs. Furthermore, several hepatic uptake and efflux transporters were targeted with pharmacological inhibitors to identify their role in the uptake of the PAs retrorsine and senecionine and in the disposition of their N-oxides (PANO). For this purpose, PA and PANO content was measured in the supernatant using LC-MS/MS. Also, PA-mediated cytotoxicity was analyzed after transport inhibition. It was found that PAs are taken up into HepaRG cells in a predominantly active and structure-dependent manner. This pattern correlates with other experimental endpoints such as cytotoxicity. Pharmacological inhibition of the influx transporters Na+/taurocholate co-transporting polypeptide (SLC10A1) and organic cation transporter 1 (SLC22A1) led to a reduced uptake of retrorsine and senecionine into HepaRG cells, emphasizing the relevance of these transporters for PA toxicokinetics. 相似文献
3.
During the service life of structural sealant glazing (SSG) facades, the load-bearing capacity of the silicone bonds needs to be guaranteed. Laboratory tests can assess the durability of SSG-systems based on mechanical characteristics of the bond after simultaneous exposure to both climatic and mechanical loads. This article studies how the material characteristics of two common structural sealants are affected by laboratory and field exposure. Dynamic mechanical analysis (DMA) confirms a reduction in the dynamic modulus of exposed silicone samples. Results from thermogravimetric analysis, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and small-angle X-ray scattering/wide-angle X-ray scattering show differences between the two sealants and indicate no/minor changes in the composition and morphology of the laboratory and field exposed sealants. Mechanical characterization methods, such as DMA, and tensile and shear testing of the structural bond, are shown to be sensitive toward the combined climatic and mechanical loadings, and are hence suitable for studying degradation mechanisms of structural sealants. 相似文献
4.
Christoph Gottschalk Aiko Huckauf Arne Dübecke Florian Kaltner Matthias Zimmermann Ines Rahaus 《Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment》2018,35(7):1366-1383
The contamination of honey with hepatotoxic pyrrolizidine alkaloids (PAs) is a well-known hazard for food safety. While management strategies and controls of the honey industry aim to reduce the PA levels, uncertainties remain with regard to the safety of regionally produced and marketed honey. In addition, a previous study showed large differences of results obtained after various periods of storage and apparent differences between the analytical results of different laboratories. Therefore, this study aimed at examining these uncertainties by monitoring the impact of storage on the PA and PA N-oxide (PANO) content of two freshly harvested honeys and on possible demixing effects caused by pollen settling. Additionally, three analytical approaches – target analysis with matrix-matched calibration or standard addition and a sum parameter method – were applied for a comparative analysis of 20 honeys harvested in summer 2016. All samples originated from Schleswig-Holstein in Northern Germany where the PA plant Jacobaea vulgaris is currently observed on a massive scale. The results of the time series analyses showed that PANO levels markedly decreased within a few weeks and practically reached the LOD 16 weeks after harvest. Tertiary PAs, by contrast, remained stable and did not increase as a consequence of PANO decrease. The experiments on a putative demixing, which may result in a heterogeneous distribution of PAs/PANOs, revealed that there was no such effect during storage of up to 12 weeks. A comparison of the PA/PANO levels obtained by different analytical approaches showed that in some cases the sum parameter method yielded much higher levels than the target approaches, whereas in other cases, the target analysis with standard addition found higher levels than the other two methods. In summary, the results of this study highlight uncertainties regarding the validity and comparability of analytical results and consequently regarding health risk assessment. 相似文献
5.
Nicolas Dolder Prof. Dr. Christoph von Ballmoos 《Chembiochem : a European journal of chemical biology》2020,21(15):2219-2224
Enzyme-mediated proton transport across biological membranes is critical for many vital cellular processes. pH-sensitive fluorescent dyes are an indispensable tool for investigating the molecular mechanism of proton-translocating enzymes. Here, we present a novel strategy to entrap pH-sensitive probes in the lumen of liposomes that has several advantages over the use of soluble or lipid-coupled probes. In our approach, the pH sensor is linked to a DNA oligomer with a sequence complementary to a second oligomer modified with a lipophilic moiety that anchors the DNA conjugate to the inner and outer leaflets of the lipid bilayer. The use of DNA as a scaffold allows subsequent selective enzymatic removal of the probe in the outer bilayer leaflet. The method shows a high yield of insertion and is compatible with reconstitution of membrane proteins by different methods. The usefulness of the conjugate for time-resolved proton pumping measurements was demonstrated by using two large membrane protein complexes. 相似文献
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Hans-Jürgen Odenthal Herbert Pfeifer Ina Lemanowicz Rainer Gorissen 《Metallurgical and Materials Transactions B》2002,33(2):163-172
The present work describes quantitative digital particle image velocimetry measurements of a full-scale water model of a thin
slab mold. Different casting speeds and two submerged entry nozzles with one and two outlet ports have been investigated.
The flow pattern of the single-port nozzle shows a counterclockwise-rotating double vortex that is nearly steady-state but
leads to high stationary surface waves. The flow jets out of the two-port nozzle oscillate and produce a transient flow pattern
with low wave amplitudes. The amplitudes for the one-port nozzle show a linear variation with the volumetric flow rate. The
experimental results lead to a good interpretation of the flow phenomena and are used to validate steady-state numerical simulations
with the commercial program, CFX, on the basis of the Reynolds equations. To describe anisotropic turbulence effects, the
Reynolds stress model (RSM) is used for the flat single-port nozzle and the standard k-ɛ model for the mold flow. The calculated mean velocities and wave amplitudes, predicted from pressure distribution at the
water surface, are generally in the consensus of the experimental data.
An erratum to this article is available at . 相似文献
9.
A system for person-independent classification of hand postures against complex backgrounds in video images is presented. The system employs elastic graph matching, which has already been successfully applied for object and face recognition. We use the bunch graph technique to model variance in hand posture appearance between different subjects and variance in backgrounds. Our system does not need a separate segmentation stage but closely integrates finding the object boundaries with posture classification. 相似文献
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