Among the TRPC subfamily of TRP (classical transient receptor potential) channels, TRPC3, -6, and -7 are gated by signal transduction pathways that activate C-type phospholipases as well as by direct ...exposure to diacylglycerols. Since TRPC6 is highly expressed in pulmonary and vascular smooth muscle cells, it represents a likely molecular candidate for receptor-operated cation entry. To define the physiological role of TRPC6, we have developed a TRPC6-deficient mouse model. These mice showed an elevated blood pressure and enhanced agonist-induced contractility of isolated aortic rings as well as cerebral arteries. Smooth muscle cells of TRPC6-deficient mice have higher basal cation entry, increased TRPC-carried cation currents, and more depolarized membrane potentials. This higher basal cation entry, however, was completely abolished by the expression of a TRPC3-specific small interference RNA in primary TRPC6 super(-) super(/) super(-) smooth muscle cells. Along these lines, the expression of TRPC3 in wild-type cells resulted in increased basal activity, while TRPC6 expression in TRPC6 super(-/-) smooth muscle cells reduced basal cation influx. These findings imply that constitutively active TRPC3-type channels, which are up-regulated in TRPC6-deficient smooth muscle cells, are not able to functionally replace TRPC6. Thus, TRPC6 has distinct nonredundant roles in the control of vascular smooth muscle tone.
Recombinant Sendai virus (rSeV) infects respiratory epithelial cells in animal models and cultures of undifferentiated human nasal cells. It was the aim of this study to investigate the capability of ...rSeV to express a transgene in human airway epithelium. Differentiated human airway epithelial cells were generated using air-liquid interface culture techniques. Application of rSeV coding for green fluorescence protein (GFP) onto the apical surface (using a multiplicity of infection of 3) resulted in expression of the transgene in more than 90% of the cells followed by decreasing numbers of positive cells during the observation time of 3 weeks. The infection of human respiratory epithelial cells is mediated by sialic acid residues at the apical surface. Despite the secretion of interleukin (IL)-8 and the replication of rSeV in the epithelial cells, the authors could not detect any cytopathic effect after the infection. In conclusion, rSeV infects differentiated human airway epithelial cells with high efficiency. Transgene expression is transient and accompanied by the secretion of an inflammatory cytokine.
Small interfering RNA (siRNA) was developed as a novel tool to inhibit gene function in human disease. The aim of the present study was to modify the function of NF-kappaB in airway epithelial cells ...by application of siRNA. 1HAEo cells were transfected with siRNA directed to the p65 subunit of NF- kappaB (siRNA.p65). Application of siRNA.p65 caused decreased levels of p65 mRNA or protein after 72 hours, as determined by quantitative RT-PCR or Western blot analysis. The tumor necrosis factor- alpha (TNF-alpha)-induced release of interleukin-6 (IL-6) and IL-8 was significantly inhibited by the application of siRNA.p65. Well-differentiated primary cells were resistant to transfection with siRNA.p65. However, when undifferentiated primary cells were transfected, an effect of the siRNA could still be observed when the cells were differentiated in an air-liquid interface culture system. In conclusion, siRNA can be used to regulate the activity of NF-kappaB in airway epithelial cells.
We used the high performance systems at HLRS in the last year for two different works. One was the hybrid implementation and optimization of ParaSPH a library for the parallel computation of particle ...simulations. We give details of the parallelization of ParaSPH for hybrid architectures (clustered SMPs) using MPI and OpenMP and discuss performance results for single node and speedups of the code on the Opteron Cluster and the NEC SX-6. The other work we present is the enhancement of an object-oriented framework for messages passing called TPO++ to support object-oriented parallel I/O.
The range of applications using our libraries and methods is extended continuously. At present it covers many different astrophysical phenomena, basically accretion procedures, impact simulations, the simulation of brittle material and the simulation of separated two phase flows, for example the injection of diesel jets. Recently we work on a solution to simulate granular media with SPH.
Proton-proton correlations at small relative momenta were measured for sup 40Ar+sup 197Au reactions at ital E/ital A=200 MeV. Comparing the correlation functions to predictions based on ...single-particle phase space distributions from microscopic Boltzmann-Uehling-Uhlenbeck and quantum-molecular-dynamics (QMD) simulations, no satisfactory agreement could be established. Calculations utilizing two-particle emission probabilities predicted by the QMD model differ significantly from the single-particle calculations and are much closer to the experimental observations at ital E/ital A=200 MeV, potentially signaling the importance of the two-particle density for the proton-proton correlation function.
Inclusive cross sections of intermediate mass fragments from the reaction {sup 40}Ar+{sup 197}Au at {ital E}/{ital A}=30 and 220 MeV were measured with a low threshold and over a large range of ...angles. The integrated cross sections are about 2 b at both energies but the emission characteristics change considerably. The increased isotropy of the angular distributions and the strongly reduced Coulomb repulsion at the higher bombarding energy suggest that the emission process evolves towards fragmentation of excited spectator matter in central ion-ion collisions.
