Molecular and Cellular Basis of Regeneration and Tissue Repair

The Xenopus tadpole is a favourable organism for regeneration research because it is suitable for a wide range of micromanipulative procedures and for a wide range of transgenic methods. Combination of these techniques enables genes to be activated or inhibited at specific times and in specific tissue types to a much higher degree than in any other organism capable of regeneration. Regenerating systems include the tail, the limb buds and the lens. The study of tail regeneration has shown that each tissue type supplies the cells for its own replacement: there is no detectable de-differentiation or metaplasia. Signalling systems needed for regeneration include the BMP and Notch signalling pathways, and perhaps also the Wnt and FGF pathways. The limb buds will regenerate completely at early stages, but not once they are fully differentiated. This provides a good opportunity to study the loss of regenerative ability using transgenic methods.     

The utility F-box for protein destruction

A signature feature of all living organisms is their utilization of proteins to construct molecular machineries that undertake the complex network of cellular activities. The abundance of a protein element is temporally and spatially regulated in two opposing aspects: de novo synthesis to manufacture the required amount of the protein, and destruction of the protein when it is in excess or no longer needed. One major route of protein destruction is coordinated by a set of conserved molecules, the F-box proteins, which promote ubiquitination in the ubiquitin-proteasome pathway. Here we discuss the functions of F-box proteins in several cellular scenarios including cell cycle progression, synapse formation, plant hormone responses, and the circadian clock. We particularly emphasize the mechanisms whereby F-box proteins recruit specific substrates and regulate their abundance in the context of SCF E3 ligases. For some exceptions, we also review how F-box proteins function through non-SCF mechanisms.     

The urokinase receptor and integrins in cancer progression

Enhanced levels of expression of urokinase receptor (uPAR) and certain integrins have been linked to cancer cell progression. This has classically been attributed to matrix degradation via the activation of the urokinase (uPA)/plasmin system and modulation of cell motility and survival through integrin engagement. More recently, uPAR has been shown to play multiple roles independent of protease activity. Specifically, uPAR has been shown to be intimately involved in the regulation of cell adhesion, migration and proliferation in part through interactions with other membrane partners, including integrins. The goal of this review is to summarize recent insights in the function of uPAR/integrin interactions, to provide a framework for understanding the importance of these interactions in the context of cancer, and to highlight its potential as a target for therapeutic intervention.     

Olfactory ensheathing cells are attracted to, and can endocytose, bacteria

Olfactory ensheathing cells (OECs) have been shown previously to express Toll-like receptors and to respond to bacteria by translocating nuclear factor-kappaB from the cytoplasm to the nucleus. In this study, we show that OECs extended significantly more pseudopodia when they were exposed to Escherichia coli than in the absence of bacteria (p=0.019). Co-immunoprecipitation showed that E. coli binding to OECs was mediated by Toll-like receptor 4. Lyso-Tracker, a fluorescent probe that accumulates selectively in lysosomes, and staining for type 1 lysosome-associated membrane proteins demonstrated that endocytosed FITC-conjugated E. coli were translocated to lysosomes. They appeared to be subsequently broken down, as shown by transmission electron microscopy. No obvious adherence to the membrane and less phagocytosis was observed when OECs were incubated with inert fluorescent microspheres. The ability of OECs to endocytose bacteria supports the notion that OECs play an innate immune function by protecting olfactory tissues from bacterial infection.     

Terahertz-field-induced insulator-to-metal transition in vanadium dioxide metamaterial

Electron-electron interactions can render an otherwise conducting material insulating, with the insulator-metal phase transition in correlated-electron materials being the canonical macroscopic manifestation of the competition between charge-carrier itinerancy and localization. The transition can arise from underlying microscopic interactions among the charge, lattice, orbital and spin degrees of freedom, the complexity of which leads to multiple phase-transition pathways. For example, in many transition metal oxides, the insulator-metal transition has been achieved with external stimuli, including temperature, light, electric field, mechanical strain or magnetic field. Vanadium dioxide is particularly intriguing because both the lattice and on-site Coulomb repulsion contribute to the insulator-to-metal transition at 340?K (ref. 8). Thus, although the precise microscopic origin of the phase transition remains elusive, vanadium dioxide serves as a testbed for correlated-electron phase-transition dynamics. Here we report the observation of an insulator-metal transition in vanadium dioxide induced by a terahertz electric field. This is achieved using metamaterial-enhanced picosecond, high-field terahertz pulses to reduce the Coulomb-induced potential barrier for carrier transport. A nonlinear metamaterial response is observed through the phase transition, demonstrating that high-field terahertz pulses provide alternative pathways to induce collective electronic and structural rearrangements. The metamaterial resonators play a dual role, providing sub-wavelength field enhancement that locally drives the nonlinear response, and global sensitivity to the local changes, thereby enabling macroscopic observation of the dynamics. This methodology provides a powerful platform to investigate low-energy dynamics in condensed matter and, further, demonstrates that integration of metamaterials with complex matter is a viable pathway to realize functional nonlinear electromagnetic composites.