33 research outputs found
Constraints on (2060) Chiron's size, shape, and surrounding material from the November 2018 and September 2019 stellar occultations
After the discovery of rings around the largest known Centaur object, (10199)
Chariklo, we carried out observation campaigns of stellar occultations produced
by the second-largest known Centaur object, (2060) Chiron, to better
characterize its physical properties and presence of material on its
surroundings. We predicted and successfully observed two stellar occultations
by Chiron. These observations were used to constrain its size and shape by
fitting elliptical limbs with equivalent surface radii in agreement with
radiometric measurements. Constraints on the (2060) Chiron shape are reported
for the first time. Assuming an equivalent radius of R =
105 km, we obtained a semi-major axis of a = 126 22 km.
Considering Chiron's true rotational light curve amplitude and assuming it has
a Jacobi equilibrium shape, we were able to derive a 3D shape with a semi-axis
of a = 126 22 km, b = 109 19 km, and c = 68 13 km, implying
in a volume-equivalent radius of R = 98 17 km, implying a density
of 1119 4 kg m. We determined the physical properties of the 2011
secondary events around Chiron, which may then be directly compared with those
of Chariklo rings, as the same method was used. Data obtained from SAAO in 2018
do not show unambiguous evidence of the proposed rings, mainly due to the large
sampling time. Meanwhile, we discarded the possible presence of a permanent
ring similar to (10199) Chariklo's C1R in optical depth and extension. Using
the first multi-chord stellar occultation by (2060) Chiron and considering it
to have a Jacobi equilibrium shape, we derived its 3D shape. New observations
of a stellar occultation by (2060) Chiron are needed to further investigate the
material's properties around Chiron, such as the occultation predicted for
September 10, 2023
Induction of ATP Release, PPIX Transport, and Cholesterol Uptake by Human Red Blood Cells Using a New Family of TSPO Ligands
Two main isoforms of the Translocator Protein (TSPO) have been identified. TSPO1 is ubiquitous and is mainly present at the outer mitochondrial membrane of most eukaryotic cells, whereas, TSPO2 is specific to the erythroid lineage, located at the plasma membrane, the nucleus, and the endoplasmic reticulum. The design of specific tools is necessary to determine the molecular associations and functions of TSPO, which remain controversial nowadays. We recently demonstrated that TSPO2 is involved in a supramolecular complex of the erythrocyte membrane, where micromolar doses of the classical TSPO ligands induce ATP release and zinc protoporphyrin (ZnPPIX) transport. In this work, three newly-designed ligands (NCS1016, NCS1018, and NCS1026) were assessed for their ability to modulate the functions of various erythrocyte’s and compare them to the TSPO classical ligands. The three new ligands were effective in reducing intraerythrocytic Plasmodium growth, without compromising erythrocyte survival. While NCS1016 and NCS1018 were the most effective ligands in delaying sorbitol-induced hemolysis, NCS1016 induced the highest uptake of ZnPPIX and NCS1026 was the only ligand inhibiting the cholesterol uptake. Differential effects of ligands are probably due, not only, to ligand features, but also to the dynamic interaction of TSPO with various partners at the cell membrane. Further studies are necessary to fully understand the mechanisms of the TSPO’s complex activation
Design, Synthesis and Biological Evaluation of Arylpyridin-2-yl Guanidine Derivatives and Cyclic Mimetics as Novel MSK1 Inhibitors. An Application in an Asthma Model
Mitogenâ and StressâActivated Kinase 1 (MSK1) is a nuclear kinase, taking part in the activation pathway of the proâinflammatory transcription factor NFâkB and is demonstrating a therapeutic target potential in inflammatory diseases such as asthma, psoriasis and atherosclerosis. To date, few MSK1 inhibitors were reported. In order to identify new MSK1 inhibitors, a screening of a library of low molecular weight compounds was performed, and the results highlighted the 6phenylpyridinâ2âyl guanidine (compound 1a, IC50~18 ÎŒM) as a starting hit for structureâactivity relationship study. Derivatives, homologues and rigid mimetics of 1a were designed, and all synthesized compounds were evaluated for their inhibitory activity towards MSK1. Among them, the noncytotoxic 2âaminobenzimidazole 49d was the most potent at inhibiting significantly: (i) MSK1 activity, (ii) the release of ILâ6 in inflammatory conditions in vitro (IC50~2 ÎŒM) and (iii) the inflammatory cell recruitment to the airways in a mouse model of asthma
Structure-activity relationship study around guanabenz identifies two derivatives retaining antiprion activity but having lost alpha 2-adrenergic receptor agonistic activity
International audienceGuanabenz (GA) is an orally active alpha 2-adrenergic agonist that has been used for many years for the treatment of hypertension. We recently described that GA is also active against both yeast and mammalian prions in an alpha 2-adrenergic receptor-independent manner. These data suggest that this side-activity of GA could be explored for the treatment of prion-based diseases and other amyloid-based disorders. In this perspective, the potent antihypertensive activity of GA happens to be an annoying side-effect that could limit its use. In order to get rid of GA agonist activity at alpha 2-adrenergic receptors, we performed a structure-activity relationship study around GA based on changes of the chlorine positions on the benzene moiety and then on the modifications of the guanidine group. Hence, we identified the two derivatives 6 and 7 that still possess a potent antiprion activity but were totally devoid of any agonist activity at alpha 2-adrenergic receptors. Similarly to GA, 6 and 7 were also able to inhibit the protein folding activity of the ribosome (PFAR) which has been suggested to be involved in prion appearance/maintenance. Therefore, these two GA derivatives are worth being considered as drug candidates