Activation Tinkercad 2005 Key
Rac and Cdc42 signals both regulate actin dynamics through individual as well as overlapping downstream effectors. These pathways are also complicated by GTPase cross-regulation (Nishimura et al., 2005; Guilluy et al., 2011). For example, early work from Alan Hall's group showed that Cdc42 activity produced lamellipodia. Only upon inhibition of Rac did Cdc42 produce filopodia, pointing to a close interplay of the two proteins (Nobes and Hall, 1995). Further complicating the pathways, in migrating cells, Rac and Cdc42 activities are spatially overlapping with the highest activity at the leading edge where they regulate actin polymerization to drive the plasma membrane in the direction of motility (Ridley et al., 2003; Machacek et al., 2009; Yang et al., 2015). Furthermore, both GTPases are also involved in other motility-relevant processes such as endocytosis, exocytosis, ECM remodeling and microtubule dynamics (Fernandez-sauze et al., 2009; Gubar et al., 2013; Bretou et al., 2014; Wojnacki et al., 2014). The multi-faceted functions of Rho family activity as well as their interconnected signaling makes it difficult to study the cause-and-effect relationships of their individual roles in directed migration. Normally, directed migration is studied by supplying cells with a graded extracellular cue while genetically and/or pharmacologically manipulating intracellular components on a whole-cell basis. While these methods have produced informative results, much is left to be learned by directly manipulating the spatial and temporal activity of individual components within cells.
Activation Tinkercad 2005 Key
We further investigated the role of cellular FN in ITSN1-Micro-induced directed migration on poly-LL using the FN-depleted cells. ITSN1-Micro and iLID-CAAX-expressing cells transfected with control siRNA or FN siRNA #1 were plated on poly-LL-coated dishes and subjected to the optotaxis assay. We found that control siRNA-transfected cells migrated with a directional bias while FN siRNA cells migrated randomly (Fig. 8F). Taken together, these data suggest that activation of Cdc42 with the ITSN1 DH/PH domain induces cellular FN deposition, which stabilizes protrusions and leads to biased directional migration in the light-gradient optotaxis experiment.
One of our most striking findings was the stark difference in Rac- and Cdc42-driven protrusion and directed migration in the absence of an ECM substrate. On poly-LL, localized Rac activity failed to produce stable lamellipodia, and asymmetric Rac activation in the optotaxis assay did not produce directed migration. On the other hand, localized Cdc42 activity produced lamellipodia and led to directed migration on poly-LL. These results prompted us to address why differential Tiam1-Micro localization (Rac activity) is insufficient to directionally bias migration in the absence of a FN substrate while differential ITSN1-Micro localization (Cdc42 activity) is sufficient without an ECM substrate.
2005: "Active Filtering of Physiological Motion in Robotized Surgery Using Predictive Control"by Romuald Ginhoux, Jacques Gangloff, Michel de Mathelin,Luc Soler, Mara M. Arenas Sanchez, Jacques Marescauxvol. 21, no. 1, pp. 67-79, 2005 [Xplore Link].
Teacher-centered instructional approaches run contrary to current research on the science of learning. Known as constructivism, the foundation of that research was presented in the seminal report, How People Learn: Brain, Mind, Experience, and School, and follow-up studies focusing on teaching and learning in mathematics, science, and history (Donovan & Bransford, 2000, 2005a, 2005b, 2005c).