Conopressin-T from Conus tulipa reveals an antagonist switch in vasopressin-like peptide

We report the discovery of conopressing-T, a novel bioactive peptide isolated from Conus tulipa venom. Conopressin-T belongs to the vasopressin-like peptide family and displays high sequence homology to the mammalian hormone oxytocin (OT) and to vasotocin, the endogenerous vasopressin analogue found in the teleost fish, the cone snail's prey

An Experimental Investigation on Fire Extinguishing Powder Efficiency

International audienceA series of large-scale tests were carried out to evaluate the effectiveness of using extinguishing powder (Purple K) to supress propane or petrol fire or to reduce emitted radiative heat flux. Three sets of different fire were carried out: a petrol leakage fire, a petrol pool fire and a liquid propane jet fire impinging a horizontal cylinder. In these tests, the powder was not able to extinguish the liquid hydrocarbons fire, but in some cases was able to extinguish the propane jet fire. In all cases, powder spray had excellent properties to reduce radiative heat flux

Chemical Synthesis of MT1 and MT7 Muscarinic Toxins: Critical Role of Arg-34 in Their Interaction with M 1 Muscarinic Receptor

International audienceTwo muscarinic toxins, MT1 and MT7, were obtained by one-step solid-phase synthesis using the 9-fluorenylmethoxycarbonyl-based method. The synthetic and natural toxins, isolated from the snake venom or recombinantly expressed, display identical physicochemical properties and pharmacological profiles. High protein recovery allowed us to specify the selectivity of these toxins for various muscarinic receptor subtypes. Thus, sMT7 has a selectivity for the M1 receptor that is at least 20,000 times that for the other subtypes. The stability of the toxin-receptor complexes indicates that sMT1 interacts reversibly with the M1 receptor, unlike sMT7, which binds it quasi-irreversibly. The effect of the synthetic toxins on the atropine-induced [3H]N-methylscopolamine (NMS) dissociation confirms that sMT7 targets the allosteric site on the M1 receptor, whereas sMT1 seems interact on the orthosteric one. The great decreases in the binding potencies observed after the R34A modification in sMT1 and sMT7 toxins highlight the functional role of this conserved residue in their interactions with the M1 receptor. Interestingly, after the R34A modification, the sMT7 toxin binds reversibly on the M1 receptor. Furthermore, the potency of sMT7-R34A for the NMS-occupied receptor is lower compared with unmodified toxin, supporting the role of this residue in the allosteric interaction of sMT7. All these results and the different charge distributions observed at the two toxin surfaces of their structure models support the hypothesis that the two toxins recognize the M1 receptor differently

Label-free microscopy of mitotic chromosomes using the polarization orthogonality breaking technique

International audienceWe report how a recently developed polarization imaging technique, implementing micro-wave photonics and referred to as orthogonality-breaking (OB) imaging, can be adapted on a classical confocal fluorescence microscope, and is able to provide informative polarization images from a single scan of the cell sample. For instance, the comparison of the images of various cell lines at different cell-cycle stages obtained by OB polarization microscopy and fluorescence confocal images shows that an endogenous polarimetric contrast arizes with this instrument on compacted chromosomes during cell division

Design of an "orthogonality breaking" polarimetric confocal microscope to study intracellular architecture dynamics

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Monocyte-derived dendritic cells from HLA-B27+ axial spondyloarthritis (SpA) patients display altered functional capacity and deregulated gene expression

International audienceINTRODUCTION:This study aimed to compare the functional capacity and gene expression profile of monocyte-derived dendritic cells (MD-DCs) in HLA-B27+ axial spondyloarthritis (SpA) patients and healthy controls.METHODS:MD-DCs were differentiated with interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for seven days, starting from purified CD14+ monocytes and stimulated with lipopolysaccharide (LPS) for six and twenty four hours. Their capacity to stimulate allogeneic CD4+ T cells from unrelated healthy donor was tested. Transcriptomic study was performed with Affymetrix HuGene 1.0 ST microarrays. Gene expression levels were compared between patients and controls using a multivariate design under a linear model (LIMMA). Real-time quantitative PCR (qRT-PCR) was performed for validation of the most striking gene expression differences.RESULTS:The stimulatory capacity of allogeneic CD4+ T cells by MD-DCs from SpA patients was decreased. Transcriptomic analysis revealed 81 genes differentially expressed in MD-DCs between SpA patients and controls (P 1.5). Four selected genes were validated by qRT-PCR:ADAMTS15, CITED2, F13A1 and SELL. Expression levels of ADAMTS15 and CITED2, encoding a metallopeptidase and a transcription factor, respectively, were inversely correlated with each other (R = 0.75, P = 0.0003). Furthermore, in silico analysis identified several genes of the Wnt signaling pathway having expression co-regulated with CITED2.CONCLUSION:This study revealed altered function and gene expression pattern in MD-DCs from HLA-B27+ axial SpA. Co-expression study showed an inverse correlation between ADAMTS15 and CITED2. Moreover, the Wnt signaling pathway appeared as deregulated in SpA MD-DCs, a finding which may be connected to Th17-driven inflammatory responses