L’interaction du TNF avec son récepteur de 55 kDa (TNF-RI) joue un rôle majeur dans le déclenchement des voies de signalisation conduisant à l’apoptose. Un des mécanismes maintenant bien connu est le recrutement, par l’intermédiaire du domaine de mort du TNF-RI, de protéines adaptatrices qui elles-mêmes recrutent la pro-caspase 8. Plus récemment, il a été montré que le TNF-RI interagit avec une autre protéine, FAN, qui active une sphingomyélinase neutre, déclenchant ainsi une autre voie de signalisation, la voie sphingomyéline-céramide. Nous démontrons maintenant que la protéine FAN est impliquée dans l’apoptose induite par les récepteurs TNF-RI et CD40.
18F-rhPSMA7 is a new theranostic PSMA-targeting agent which allow fast radiolabeling with 18F and radiometals. In addition, the tracer shows only minimal renal excretion. This retrospective analysis investigates the efficacy of 18F-rhPSMA7 PET/CT in biochemical recurrence (BCR).
Pestalone (1) is a prominent marine natural product first isolated by M. Cueto et al. in 2001 from a co-fermentation of a marine fungus with a marine bacterium. For more than 10 years, 1 had been considered as a promising new antibiotic compound, the reported MIC against methicillin-resistant Staphylococcus aureus (MRSA) being 37 ng/mL. After overcoming the limited availability of 1 by total synthesis (N. Slavov et al., 2010) we performed new biological tests, which did not confirm the expected degree of antibiotic activity. The observed activity of pestalone against different MRSA strains was 3-10 μg/mL, as determined independently in two laboratories. A number of synthetic derivatives of 1 including pestalachloride A and other isoindolinones (formed from 1 by reaction with amines) did not exhibit higher activities as compared to 1 against MRSA and a series of plant pathogens.
The T-cell growth factor (TCGF) receptor on phytohemagglutinin-activated normal peripheral blood T-cells is characterized as a glycoprotein with an apparent Mr = 55,000 that contains N-linked and O-linked carbohydrate with only approximately 33,000 daltons of peptide structure (p33) as evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. There are two N-linked glycosylated intermediate precursor forms (apparent Mr = 35,000 (p35) and 37,000 (p37]. This receptor differs from the TCGF receptor on HUT-102B2 cells (apparent Mr = 50,000) because of differences in post-translational processing. Experiments with the carboxylic ionophore monensin demonstrate blockade of the transition of the p35 and p37 receptor precursor forms to the mature receptor, presumably secondary to inhibition of Golgi-associated receptor processing. We identify the primary translation product of TCGF receptor mRNA as intermediate in size between the p33 and the p35/p37 forms. We further demonstrate that the p33, p35, and p37 precursor forms, but not the primary translation product, are all capable of binding TCGF. Thus, the removal of the signal peptide and/or conformational changes of the primary translation product are necessary for ligand binding; however, the extensive post-translational modifications are not. Lastly, we demonstrate that at least some TCGF receptors are phosphorylated and sulfated, and that TCGF receptors on phytohemagglutinin-activated normal T-cells are more heavily sulfated than those on HUT-102B2 cells.
Ziel/Aim To perform precise and individualized dosimetry in Selective Internal Radiotherapy (SIRT) registering high-quality diagnostic imaging with planning SPECT/CT can enable voxel-based calculations and does optimize treatment. We present a fully automatic framework for registering diagnostic MRI to low-dose CT which yields lower target registration error (TRE) than conventional intensity-based methods and can reduce human interaction.
Ziel/Aim Thyroid volumetry is crucial in diagnosis, treatment and monitoring of thyroid diseases. However, conventional thyroid volumetry with 2D ultrasound (US) is highly operator-dependent. This study compares 2D US and tracked 3D US with an automatic thyroid segmentation regarding inter- and intraobserver variability. Volume reference standard was MRI.
Abstract Although numerous pathogenic changes within the mitochondrial respiratory chain (RC) have been associated with an elevated occurrence of apoptosis within the affected tissues, the mechanistic insight into how mitochondrial dysfunction initiates apoptotic cell death is still unknown. In this study, we show that the specific alteration of the cytochrome c oxidase (COX), representing a common defect found in mitochondrial diseases, facilitates mitochondrial apoptosis in response to oxidative stress. Our data identified an increased ceramide synthase 6 (CerS6) activity as an important pro-apoptotic response to COX dysfunction induced either by chemical or genetic approaches. The elevated CerS6 activity resulted in accumulation of the pro-apoptotic C 16 : 0 ceramide, which facilitates the mitochondrial apoptosis in response to oxidative stress. Accordingly, inhibition of CerS6 or its specific knockdown diminished the increased susceptibility of COX-deficient cells to oxidative stress. Our results provide new insights into how mitochondrial RC dysfunction mechanistically interferes with the apoptotic machinery. On the basis of its pivotal role in regulating cell death upon COX dysfunction, CerS6 might potentially represent a novel target for therapeutic intervention in mitochondrial diseases caused by COX dysfunction.
