Design and sizing of an airship supported by CAE

FLYWI

Fgf-3 and Fgf-4 Elicit Distinct Oncogenic Properties in Mouse Mammary Myoepithelial Cells

Fibroblast Growth Factors 3 (FGF-3) and 4 (FGF-4) were compared for the effects they each exert on EF43 mouse cells. This non-transformed mammary cell line appears to be myoepithelial mainly because it expresses alpha-smooth muscle actin. The EF43 cells were infected with similar vectors that carry either the short fgf-3 sequence (the product of which goes into the secretory pathway), fgf-4 or the selection gene only as control. In syngeneic animals, EF43.fgf-3 cells were tumorigenic only when orthotopically implanted whereas EF43.fgf-4 cells invariably gave rise to aggressive tumors. However, both tumor types were metastatic as evidenced by the blue micrometastases observed when the implanted cells expressed lacZ. In vitro, the FGF-3 producing cells were strongly invasive in matrigel coated chambers whereas the EF43.fgf-4 cells only were invasive in type I-collagen gels. Interestingly, FGF-3 production greatly stimulated the synthesis of pro-MMP-9 (Matrix Metalloprotease-9) and, to a lesser extent, that of pro-MMP-2. FGF-3 also up-regulated the production of plasminogen activators. In contrast, FGF-4 had no effect on these secretions and the medium conditioned by the EF43.fgf-4 cells displayed the largest plasminogen activator-inhibitor activity. These results show that FGF-3 and FGF-4 have distinct mechanisms of action on myoepithelial cells

TRIP6, a novel molecular partner of the MAGI-1 scaffolding molecule, promotes invasiveness

We recently established the critical role of the PTEN/MAGI-1b signalosome in stabilization of cell-cell contacts and suppression of invasiveness. The PTEN tumor suppressor is recruited to E-cadherin junctional complexes through the binding to the second PDZ domain of the MAGI-1b scaffolding molecule, whereas beta-catenin interacts with the fifth PDZ domain. To identify additional effectors of this signalosome, we used yeast 2-hybrid screening. Among the clones identified, we focused on TRIP6, which belongs to the zyxin family of proteins. We demonstrated that TRIP6 interacted directly with MAGI-1b by binding to its fifth PDZ domain. Ectopic expression of TRIP6 induced invasiveness in the epithelial MDCK and MDCKts-src cells in a PI3-kinase-and a NF-kappa B-dependent manner and impaired cell-cell aggregation at least in part by uncoupling adherens junctional complexes from the cytoskeleton. The TRIP6Stop473 mutant, which lacks the PDZ binding motif, was still able to increase NF-kappa B and Akt activities but did not promote invasiveness or interfere with cell-cell aggregation. Intracellular delivery of competing peptides corresponding to TRIP6 or beta-catenin C terminus restored invasive properties in MDCKts-src TRIP6Stop473 cells, highlighting the requirement of PDZ scaffolds in junctional complexes activity. TRIP6 overexpression in colon tumors suggest its critical role in cancer progression.-Chastre, E., Abdessamad, M., Kruglov, A., Bruyneel, E., Bracke, M., Di Gioia, Y., Beckerle, M. C., van Roy, F., Kotelevets, L. TRIP6, a novel molecular partner of the MAGI-1 scaffolding molecule, promotes invasiveness

Idiopathic scoliosis and balance organisation in seated position on a seesaw

The aim was to determine the biomechanical processes involved in postural regulation when self-imposed disturbances occur in the seated position in the antero-posterior direction. Twelve female adolescents with right thoracic scoliosis (SG) (Cobb = 30.4° ± 9.7) and 15 control adolescents (CG) were included in this study. The ground reaction forces (GRF) were studied whilst the subjects maintained their balance in the sitting position on a seesaw. Six conditions were tested: eyes open and closed; with an additional load placed on the subject’s right or left shoulder; and with an additional load on the subject’s right or left pelvis. The SG showed significantly higher force amplitudes and variability and fewer oscillations than the CG in all the conditions. In the SG, the time analysis showed that the duration of the GRF was significantly higher in forward and left directions. Whatever the condition tested, the intra-group differences were not significant. The scoliotic patients in seated position were characterised by larger changes of the GRF, especially with a postural control in the forward and left directions, corresponding to that on the concave side of their spinal curvature. No significant differences were found to exist between the various conditions (load and unload, eyes open and eyes closed). Clinical tests and rehabilitation methods should include assessments of seated patients’ spatio-temporal adaptation to GRF

Idiopathic scoliosis: relations between the Cobb angle and the dynamical strategies when sitting on a seesaw

The aim of this study was to determine the influence of the severity of the spinal curve on the postural regulation when self-imposed disturbances occur in a seated position in anteroposterior (AP) and mediolateral (ML) orientations. Twelve female adolescents with a right thoracic scoliosis (Cobb = 30.4° ± 9.7) were included in this study. The ground reaction forces (GRF) were studied while the subjects were maintaining their sitting on a seesaw (ML or AP destabilisation). Five conditions were tested: eyes open; with additional loads placed onto the subject’s right or left shoulder; or onto the subject’s right or left pelvis. We tested the correlation between the Cobb angle and the postural parameters (index of performance and GRF variability) for each condition. When the destabilisation was AP, the Cobb angle was significantly correlated with GRF variability and anterior and concavity index of performance. Two conditions showed higher correlations: stabilisation with the concavity pelvis load (GRF variability) and the open eyes (index of performance). In contrast, whatever the condition tested was, no link was found when the destabilisations were applied in ML direction. The destabilisation in a seated position highlights the influence of the curve severity on the postural organisation. In seated position, the postural control strategies specific to the scoliotic patients were always correlated by severity of curve, especially when the destabilisation is applied in AP directions. This study showed that the unstable seating position can be considered as a pertinent paradigm to help finding a postural clinical index for adolescent idiopathic scoliosis

Identification of a novel cardenolide (2''-oxovoruscharin) from Calotropis procera and the hemisynthesis of novel derivatives displaying potent in vitro antitumor activities and high in vivo tolerance: structure-activity relationship analyses.

Analysis of the methanolic extract of Calotropis procera root barks enabled the identification of a novel cardenolide (2''-oxovoruscharin) to be made. Of the 27 compounds that we hemisynthesized, one (23) exhibited a very interesting profile with respect to its hemisynthetic chemical yield, its in vitro antitumor activity, its in vitro inhibitory influence on the Na+/K+-ATPase activity, and its in vivo tolerance. Compound 23 displayed in vitro antitumor activity on a panel of 57 human cancer cell lines similar to taxol, and higher than SN-38 (the active metabolite of irinotecan), two of the most potent drugs used in hospitals to combat cancer.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe