Bone Morphogenetic Proteins (BMPs) are morphogens that play a major role in regulating development and homeostasis. Although BMPs are used for the treatment of bone and kidney disorders, their ...clinical use is limited due to the supra-physiological doses required for therapeutic efficacy causing severe side effects. Because recombinant BMPs are expensive to produce, small molecule activators of BMP signaling would be a cost-effective alternative with the added benefit of being potentially more easily deliverable. Here, we report our efforts to identify small molecule activators of BMP signaling. We have developed a cell-based assay to monitor BMP signaling by stably transfecting a BMP-responsive human cervical carcinoma cell line (C33A) with a reporter construct in which the expression of luciferase is driven by a multimerized BMP-responsive element from the Id1 promoter. A BMP-responsive clone C33A-2D2 was used to screen a bioactive library containing ~5,600 small molecules. We identified four small molecules of the family of flavonoids all of which induced luciferase activity in a dose-dependent manner and ventralized zebrafish embryos. Two of the identified compounds induced Smad1, 5 phosphorylation (P-Smad), Id1 and Id2 expression in a dose-dependent manner demonstrating that our assays identified small molecule activators of BMP signaling.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
During the synthesis of geopolymer materials, all of the phenomena and reactions that occur should be included in the analysis of the synthesis. This work aims to study the role that siliceous ...species play in an activation solution in the presence of pure metakaolin. The formation of a gel phase during the synthesis of a K-geopolymer was shown. Different mixtures were analyzed by infrared spectroscopy. During material consolidation, there is always competition between the geopolymer network and the gel that is governed by a change in the siliceous species. The heat treatment of various gels and solids provided evidence of various networks in geopolymer materials. Finally, the change in the crystallinity of the silica in the activation solution led to a change in the kinetics of the polycondensation reactions, in agreement with previous work.
BACKGROUND:The broad genetic divergence of HIV-1/O relative to HIV-1/M has important implications for diagnosis, monitoring and treatment. Despite this divergence, some HIV-1/M+O dual infections and ...HIV-1/MO recombinant forms have been reported, mostly in Cameroon, where both groups are prevalent. Here, we describe the characteristics of such infections detected in France in 10 new patients, and discuss their implications for biological and clinical practice, owing to the presence of group O species.
METHODS:The French National Reference Centre for HIV received samples within the framework of mandatory notification of HIV infections, and for expert analysis. A strategy combining serotyping, viral quantification, group-specific molecular amplification and whole-genome sequencing was used for strain characterization and complementary investigations.
RESULTS:We identified one patient with M+O infection, three patients with M+O infection associated with an MO recombinant, and six patients with only an MO recombinant. These atypical infections were detected upon strain characterization (n = 4) or because of anomalies during patient monitoring (n = 6). We identified eight new URF_MO, all but one originating from Cameroon. Interestingly, two distinct recombinant strains were found in two unrelated patients, representing possible precursors of a CRF_MO.
CONCLUSION:Our work highlights the fact that the continuous evolution of HIV can hinder diagnosis and complicate clinical practice. We stress that unexpected results during diagnosis or monitoring necessitate further serological and molecular exploration, these atypical infections influence biological and therapeutic management and necessitate appropriate tools, and specific surveillance is necessary, especially as the frequency of such infections may be underestimated.
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