T helper 9 (T
9) cells promote allergic tissue inflammation and express the type 2 cytokines, IL-9 and IL-13, as well as the transcription factor, PPAR-γ. However, the functional role of PPAR-γ in ...human T
9 cells remains unknown. Here, we demonstrate that PPAR-γ drives activation-induced glycolysis, which, in turn, promotes the expression of IL-9, but not IL-13, in an mTORC1-dependent manner. In vitro and ex vivo experiments show that the PPAR-γ-mTORC1-IL-9 pathway is active in T
9 cells in human skin inflammation. Additionally, we find dynamic regulation of tissue glucose levels in acute allergic skin inflammation, suggesting that in situ glucose availability is linked to distinct immunological functions in vivo. Furthermore, paracrine IL-9 induces expression of the lactate transporter, MCT1, in T
cells and promotes their aerobic glycolysis and proliferative capacity. Altogether, our findings uncover a hitherto unknown relationship between PPAR-γ-dependent glucose metabolism and pathogenic effector functions in human T
9 cells.
Xenotransplantation using pig organs has achieved survival times up to 195 days in pig orthotopic heart transplantation into baboons. Here we demonstrate that in addition to an improved ...immunosuppressive regimen, non-ischaemic preservation with continuous perfusion and control of post-transplantation growth of the transplant, prevention of transmission of the porcine cytomegalovirus (PCMV) plays an important role in achieving long survival times. For the first time we demonstrate that PCMV transmission in orthotopic pig heart xenotransplantation was associated with a reduced survival time of the transplant and increased levels of IL-6 and TNFα were found in the transplanted baboon. Furthermore, high levels of tPA-PAI-1 complexes were found, suggesting a complete loss of the pro-fibrinolytic properties of the endothelial cells. These data show that PCMV has an important impact on transplant survival and call for elimination of PCMV from donor pigs.
The present experimental work focuses on revealing the influence of hydrogen (H2) on the interfacial tension, viscosity, density, and thermal diffusivity of the liquid phase of the energy carrier ...methanol under saturation conditions, which has been only fragmentarily investigated so far, and on providing corresponding H2 solubility and Fick diffusion coefficient data. For this, conventional methods, dynamic light scattering from the liquid bulk and from the liquid-gas interface as well as Raman spectroscopy were used at temperatures up to 393 K and pressures up to 8 MPa. The results show that with H2 under saturation conditions, the viscosity and density of liquid methanol are nearly pressure-independent, whereas the interfacial tension is reduced by about 6% at 8 MPa. The latter effect is temperature-independent despite the increasing H2 concentration with increasing temperature, which may be associated with a counteracting influence of temperature on a presumed surface enrichment of H2.
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•Experimental data on various thermophysical properties up to 423 K and 8 MPa.•Small influence of saturation with hydrogen on liquid viscosity and density of methanol.•Decreasing interfacial tension with increasing hydrogen pressure by up to 6%.•First temperature-dependent data for Fick diffusion coefficients for H2 in methanol.•Successful calibration of Raman spectroscopy for measuring hydrogen concentration.
Electrochemical machining (ECM) is an unconventional manufacturing method based on the anodic dissolution of the metal workpiece material. A superimposed magnetic field causes additional body forces ...within the working gap influencing the electrolyte convection and consequently afecting the electrochemical kinetics and gas transport. In this study, a multiphysics simulation model was built to analyze the interactions between the magnetic field characteristics, the convective heat- and charge-transport in the working gap and the electrochemical workpiece shaping. Therefore, the Lorentz force and Kelvin force were considered. In addition, machined geometries and surface properties were measured and related to the simulation findings.
Metalworking operations rely on the successful application of metalworking fluids (MWFs) for effective and efficient operation. Processes such as grinding or drilling often require the use of MWFs ...for cooling, lubrication, and chip removal. Electrochemical machining processes require electrolyte flow to operate. However, in those machining operations, a fundamental understanding of the mode of action of MWF is lacking due to the unknown flow dynamics and its interaction with the material removal during the process. Important information on the behaviour of MWFs during machining can be obtained from specific experimental flow visualisation studies. In this paper, promising flow visualisation analysis techniques applied to exemplary machining processes (grinding, sawing, drilling, and electrochemical machining) are presented and discussed. Shadowgraph imaging and flow measurements, e.g., particle image velocimetry, allow the identification of typical flow and MWF operating regimes in the different machining processes. Based on the identification of these regimes, efficient machining parameters and MWF applications can be derived. In addition, detailed experimental analyses of MWFs provide essential data for the input and validation of model development and numerical simulations within the Priority Programme SPP 2231 FluSimPro.
Left ventricular dysfunction is a frequent and potentially severe side effect of many tyrosine kinase inhibitors (TKI). The mode of toxicity is not identified, but may include impairment of ...mitochondrial or sarcomeric function, autophagy or angiogenesis, either as an on-target or off-target mechanism.
We studied concentration-response curves and time courses for nine TKIs in three-dimensional, force generating engineered heart tissue (EHT) from neonatal rat heart cells. We detected a concentration- and time-dependent decline in contractile force for gefitinib, lapatinib, sunitinib, imatinib, sorafenib, vandetanib and lestaurtinib and no decline in contractile force for erlotinib and dasatinib after 96 hours of incubation. The decline in contractile force was associated with an impairment of autophagy (LC3 Western blot) and appearance of autophagolysosomes (transmission electron microscopy).
This study demonstrates the feasibility to study TKI-mediated force effects in EHTs and identifies an association between a decline in contractility and inhibition of autophagic flux.
PVP-capped silver nanoparticles with a diameter of the metallic core of 70 nm, a hydrodynamic diameter of 120 nm and a zeta potential of -20 mV were prepared and investigated with regard to their ...biological activity. This review summarizes the physicochemical properties (dissolution, protein adsorption, dispersability) of these nanoparticles and the cellular consequences of the exposure of a broad range of biological test systems to this defined type of silver nanoparticles. Silver nanoparticles dissolve in water in the presence of oxygen. In addition, in biological media (i.e., in the presence of proteins) the surface of silver nanoparticles is rapidly coated by a protein corona that influences their physicochemical and biological properties including cellular uptake. Silver nanoparticles are taken up by cell-type specific endocytosis pathways as demonstrated for hMSC, primary T-cells, primary monocytes, and astrocytes. A visualization of particles inside cells is possible by X-ray microscopy, fluorescence microscopy, and combined FIB/SEM analysis. By staining organelles, their localization inside the cell can be additionally determined. While primary brain astrocytes are shown to be fairly tolerant toward silver nanoparticles, silver nanoparticles induce the formation of DNA double-strand-breaks (DSB) and lead to chromosomal aberrations and sister-chromatid exchanges in Chinese hamster fibroblast cell lines (CHO9, K1, V79B). An exposure of rats to silver nanoparticles in vivo induced a moderate pulmonary toxicity, however, only at rather high concentrations. The same was found in precision-cut lung slices of rats in which silver nanoparticles remained mainly at the tissue surface. In a human 3D triple-cell culture model consisting of three cell types (alveolar epithelial cells, macrophages, and dendritic cells), adverse effects were also only found at high silver concentrations. The silver ions that are released from silver nanoparticles may be harmful to skin with disrupted barrier (e.g., wounds) and induce oxidative stress in skin cells (HaCaT). In conclusion, the data obtained on the effects of this well-defined type of silver nanoparticles on various biological systems clearly demonstrate that cell-type specific properties as well as experimental conditions determine the biocompatibility of and the cellular responses to an exposure with silver nanoparticles.
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