Cells activated for wound repair have the potential to direct collective invasion of an epithelium.

Mechanisms regulating how groups of cells are signaled to move collectively from their original site and invade surrounding matrix are poorly understood. Here we develop a clinically relevant ex vivo injury invasion model to determine whether cells involved in directing wound healing have invasive function and whether they can act as leader cells to direct movement of a wounded epithelium through a three-dimensional (3D) extracellular matrix (ECM) environment. Similar to cancer invasion, we found that the injured cells invade into the ECM as cords, involving heterotypical cell-cell interactions. Mesenchymal cells with properties of activated repair cells that typically locate to a wound edge are present in leader positions at the front of ZO-1-rich invading cords of cells, where they extend vimentin intermediate filament-enriched protrusions into the 3D ECM. Injury-induced invasion depends on both vimentin cytoskeletal function and MMP-2/9 matrix remodeling, because inhibiting either of these suppressed invasion. Potential push and pull forces at the tips of the invading cords were revealed by time-lapse imaging, which showed cells actively extending and retracting protrusions into the ECM. This 3D injury invasion model can be used to investigate mechanisms of leader cell-directed invasion and understand how mechanisms of wound healing are hijacked to cause disease

Disruption of Spectrin-Like Cytoskeleton in Differentiating Keratinocytes by PKCδ Activation Is Associated with Phosphorylated Adducin

Spectrin is a central component of the cytoskeletal protein network in a variety of erythroid and non-erythroid cells. In keratinocytes, this protein has been shown to be pericytoplasmic and plasma membrane associated, but its characteristics and function have not been established in these cells. Here we demonstrate that spectrin increases dramatically in amount and is assembled into the cytoskeleton during differentiation in mouse and human keratinocytes. The spectrin-like cytoskeleton was predominantly organized in the granular and cornified layers of the epidermis and disrupted by actin filament inhibitors, but not by anti-mitotic drugs. When the cytoskeleton was disrupted PKCδ was activated by phosphorylation on Thr505. Specific inhibition of PKCδ(Thr505) activation with rottlerin prevented disruption of the spectrin-like cytoskeleton and the associated morphological changes that accompany differentiation. Rottlerin also inhibited specific phosphorylation of the PKCδ substrate adducin, a cytoskeletal protein. Furthermore, knock-down of endogenous adducin affected not only expression of adducin, but also spectrin and PKCδ, and severely disrupted organization of the spectrin-like cytoskeleton and cytoskeletal distribution of both adducin and PKCδ. These results demonstrate that organization of a spectrin-like cytoskeleton is associated with keratinocytes differentiation, and disruption of this cytoskeleton is mediated by either PKCδ(Thr505) phosphorylation associated with phosphorylated adducin or due to reduction of endogenous adducin, which normally connects and stabilizes the spectrin-actin complex

Common Fixed Point Theorems of Integral Type for OWC Mappings under Relaxed Condition

In this paper, we prove a common fixed point theorem for a pair of occasionally weakly compatible (owc) self mappings satisfying a mixed contractive condition of integral type without using the triangle inequality. We prove also analogous results for two pairs of owc self mappings by assuming symmetry only on the set of points of coincidence. These results unify, extend and complement many results existing in the recent literature. Finally, we give an application of our results in dynamic programming

Fixed Point Theorems for (ψ, ϕ)-Contractive maps in Weak non-Archimedean Fuzzy Metric Spaces and Application

The present study introduce the notion of (ψ, ϕ)-Contractive maps in weak non-Archimedean fuzzy metric spaces to derive a common fixed point theorem which complements and extends the main theorems of [C.Vetro, Fixed points in weak non-Archimedean fuzzy metric spaces, Fuzzy Sets and System, 162 (2011), 84-90] and [D.Mihet, Fuzzy ψ-contractive mappings in non-Archimedean fuzzy metric spaces, Fuzzy Sets and System, 159 (2008) 739-744]. We support our result by establishing an application to product spaces

A fixed point theorem in G-metric spaces via alpha-series

In the context of G-metric spaces we prove a common fixed point theorem for a sequence of self mappings using a new concept of alpha-series

Some common fixed point theorems for owc mappings with applications

Starting from the setting of fuzzy metric spaces, we give some new common fixed point theorems for a pair of occasionally weakly compatible (owc) self-mappings satisfying a mixed contractive condition. In proving our results, we do not need to use the triangular inequality. Also we obtain analogous results for two pairs of owc self-mappings by assuming symmetry only on the set of points of coincidence. These results unify, extend and complement some results existing in the literature. Finally, we give some applications of our results