The Gravitational Behaviour of Antihydrogen at Rest experiment - GBAR - is designed to perform a direct measurement of the weak equivalence principle on antimatter by measuring the acceleration ( ) ...of antihydrogen atoms in free fall. Its originality is to produce + ions and use sympathetic cooling to minimize the initial velocity. These ions are produced using charge exchange reactions with a dense positronium cloud, created by an intense pulse of electron-linac-produced positrons that are accumulated in a Penning-Malmberg trap.
The aim of the GBAR (Gravitational Behavior of Antimatter at Rest) experiment is to measure the free fall acceleration of an antihydrogen atom, in the terrestrial gravitational field at CERN and ...therefore test the Weak Equivalence Principle with antimatter. The aim is to measure the local gravity with a 1% uncertainty which can be reduced to few parts of 10 -3 .
The btg1 (B-cell translocation gene 1) gene coding sequence was isolated from a translocation break point in a case of B-cell chronic lymphocytic leukaemia. We have already shown that BTG1, ...considered as an antiproliferative protein, strongly stimulates myoblast differentiation. However, the mechanisms involved in this influence remained unknown. In cultured myoblasts, we found that BTG1 stimulates the transcriptional activity of nuclear receptors (T3 and all-trans retinoic acid receptors but not RXRalpha and PPARgamma), c-Jun and myogenic factors (CMD1, Myf5, myogenin). Immunoprecipitation experiments performed in cells or using in vitro-synthesized proteins and GST pull-down assays established that BTG1 directly interacts with T3 and all-trans retinoic acid receptors and with avian MyoD (CMD1). These interactions are mediated by the transactivation domain of each transcription factor and the A box and C-terminal part of BTG1. NCoR presence induces the ligand dependency of the interaction with nuclear receptors. Lastly, deletion of BTG1 interacting domains abrogates its ability to stimulate nuclear receptors and CMD1 activity, and its myogenic influence. In conclusion, BTG1 is a novel important coactivator involved in the regulation of myoblast differentiation. It not only stimulates the activity of myogenic factors, but also of nuclear receptors already known as positive myogenic regulators.
The ALPHA Collaboration, based at the CERN Antiproton Decelerator, has recently implemented a novel beamline for low-energy (\(\lesssim\) 100 eV) positron and antiproton transport between cylindrical ...Penning traps that have strong axial magnetic fields. Here, we describe how a combination of semianalytical and numerical calculations were used to optimise the layout and design of this beamline. Using experimental measurements taken during the initial commissioning of the instrument, we evaluate its performance and validate the models used for its development. By combining data from a range of sources, we show that the beamline has a high transfer efficiency, and estimate that the percentage of particles captured in the experiments from each bunch is (78 \(\pm\) 3)% for up to \(10^{5}\) antiprotons, and (71 \(\pm\) 5)% for bunches of up to \(10^{7}\) positrons.
Drug delivery nanosystems are currently used in human therapy. In preliminary studies we have observed that Eudragit
® RS nanoparticles, prepared by nanoprecipitation or double emulsion techniques, ...are cytotoxic for NR8383 rat macrophages. In this study, we expand our previous analysis and suggest that unloaded Eudragit
® RS nanoparticles prepared by nanoprecipitation (NP/ERS) may induce important morphological and biochemical cellular modifications leading to cellular death. In NR8383 rat macrophages cell line exposed to doses varying from 15 to 100
μg/mL, NP/ERS nanoparticles are internalized inside the cells, reach the mitochondria and alter the structure of these organelles. In addition, the exposure to nanoparticles induces cellular autophagy as demonstrated by electron microscopy analysis, microchip array, qRT-PCR and Western blot assays. Although toxicity of nanoparticles has already been evidenced, it is the first time that results show clearly that the toxicity of polymeric nanovectors may be related to an activation of autophagy.
S-nitrosoglutathione (GSNO) is a potential therapeutic for infectious disease treatment because of its pivotal role in macrophage-mediated inflammatory responses and host defense in addition to ...direct antibacterial activities. In this study, sterically stabilized cationic liposomes (SSCL) and sterically stabilized anionic liposomes (SSAL) were developed as nanocarriers for macrophage targeting. Elaborated liposomes were characterized in terms of size, zeta potential, morphology, encapsulation efficiency, in vitro drug release behavior and cytotoxicity. Their versatility in targeting monocytes/macrophages was determined by confocal laser scanning microscopy and transmission electron microscopy. Flow cytometry revealed that cellular uptake of both SSCL and SSAL was governed by several endocytic clathrin- and caveolae-dependent mechanisms. Quantitative assessments of intracellular nitric oxide demonstrated highly efficient uptake of GSNO-loaded SSCL that was twenty-fold higher than that of GSNO-free molecules. GSNO-loaded SSCL displayed strong bacteriostatic effects on Staphylococcus aureus and Pseudomonas aeruginosa, which can be involved in pulmonary infectious diseases. These results reveal the potential of liposomal GSNO as an anti-infective therapeutic due to its macrophage targeting capacity and direct antibacterial effects.
Mitochondrial dysfunctions are frequently reported in cancer cells, but their direct involvement in tumorigenesis remains unclear. To understand this relation, we stimulated mitochondrial activity by ...overexpression of the mitochondrial triiodothyronine receptor (p43) in human dermal fibroblasts. In all clones, this stimulation induced morphologic changes and cell fusion in myotube-like structures associated with the expression of several muscle-specific genes (Myf5, desmin, connectin, myosin, AchRalpha). In addition, these clones displayed all the in vivo and in vitro features of cell transformation. This phenotype was related to an increase in c-Jun and c-Fos expression and extinction of tumor suppressor gene expression (p53, p21WAF1, Rb3). Lastly, reactive oxygen species (ROS) production was increased in positive correlation to the stimulation of mitochondrial activity. The direct involvement of mitochondrial activity in this cell behavior was studied by adding chloramphenicol, an inhibitor of mitochondrial protein synthesis, to the culture medium. This inhibition resulted in partial restoration of the normal phenotype, with the loss of the ability to fuse, a strong decrease in muscle-specific gene expression, and potent inhibition of the transformed phenotype. However, expression of tumor suppressor genes was not restored. Similar results were obtained by using N-acetylcysteine, an inhibitor of ROS production. These data indicate that stimulation of mitochondrial activity in human dermal fibroblasts induces cell transformation through events involving ROS production.
IntroductionAdvanced breast cancers do not respond well to therapies and represent a relevant focus for studying molecular mechanisms involved in the tumour progression and drug resistance. The ...transcription factor NF-κB is often activated constitutively in aggressive breast cancer cells and plays a significant role by inducing many target genes involved in tumour progression and drug resistance. Mechanisms controlling constitutive NF-kB activation are not all clearly understood. Among them, repression of the gene encoding the NF-κB inhibitor, IκBα is not well known. This protein controls NF-κB activation by sequestering it in the cytoplasmic compartment. The present study reports the identification of the hnRNP K/J protein, which is initially known for its role in mRNA splicing and translation, as a repressor of the IκBα gene expression.Material and methodsIdentification of hnRNP K/J protein on the IκBα promoter was carried out by DNA pull-down coupled with a mass spectrometry analysis, and chromatin immunoprecipitation (ChIP) using a specific polyclonal antibodies. The hnRNP K/J protein was overexpressed in breast cancer cell lines by transient transfection, and consequence on the IκBα expression and the proximal IκBα promoter activity was evaluated by RT-qPCR and gene reporter assay, respectively. The hnRNP K/J protein localization was visualised in cells by Western blotting using nuclear and cytoplasmic extracts.Results and discussionsThe IκBα gene is expressed higher in nonaggressive compared to aggressive breast cancer cells. We used previous data showing the importance of the proximal promoter at position −495 from the transcription site for DNA pull-down with nuclear protein extract from MCF-7 cells. Mass spectrometry analysis led to identify hnRNP K/J protein, whose the binding to this region of the proximal IκBα promoter was confirmed by ChIP. The IκBα expression at mRNA level and proximal IκBα promoter activity was strongly decreased in hnRNP K/J-overexpressing breast cancer cells, in contrast to the respective parental cells, suggesting the role of hnRNP K/J protein as a gene repressor.ConclusionThe identification of hnRNP K/J as a repressor of IκBα gene expression depicts a new molecular mechanism, which may contribute to the high constitutive NF-kB activation in aggressive breast cancer cells and suggests to take it into account in the development of new therapies targeting NF-kB pathway in advanced breast cancers.
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