Semaphorins act as attractive and repulsive guidance signals during the development of cortical projections

Members of the semaphorin family have been implicated in mediating axonal guidance in the nervous system by their ability to collapse growth cones and to function as chemorepellents. The present findings show that recombinant Semaphorin D has similar effects on cortical axons and, in addition, inhibits axonal branching. In contrast, semaphorin E acts as an attractive guidance signal for cortical axons. Attractive effects were only observed when growth cones encountered increasing concentrations or a patterned distribution of Semaphorin E, but not when they are exposed to uniform concentrations of this molecule. Specific binding sites for Semaphorin D and Semaphorin E were present on cortical fibers both in vitro and in vivo at the time when corticofugal projections are established. In situ hybridization analysis revealed that the population of cortical neurons used in our experiments express neuropilin-1 and neuropilin-2, which are essential components of receptors for the class III semaphorins. Moreover, semD mRNA was detected in the ventricular zone of the neocortex whereas semE mRNA was restricted to the subventricular zone. Taken together, these results indicate that semaphorins are bifunctional molecules whose effects depend on their spatial distribution. The coordinated expression of different semaphorins, together with their specific activities on cortical axons, suggests that multiple guidance signals contribute to the formation of precise corticofugal pathways.     

Size-exclusion phases and repulsive protein--polymer interaction/recognition

Size-dependent exclusion of macromolecules from gel matrices has long been discussed in terms of pore models. An alternate approach is to calculate the partition coefficient of the distributed species between the matrix material and the mobile phase assuming that the gel can be treated as a polymer solution of appropriate concentration and molecular weight. This approach is particularly appealing in attempting to predict the behaviour of 'tentacle' phases in which the matrix contains anchored linear neutral polymers. The mean field theory of polymer solution is used to predict K, the partition coefficient of a polymer molecule distributing between the gel and mobile phases. The reduction in entropy suffered by the macromolecule in the gel phase is sufficient to produce an exponential dependence of K on the molecular weight of the partitioning species. The enthalpy of interaction between the gel polymer and the distributed species provides a parameter which describes the specificity or recognition in the interaction. The predicted linear dependence of in K on protein molecular weight is satisfactorily borne out by a data set on eight standard proteins chromatographed on four separate gel types.     

Threshold stresses for dislocation climb over hard particles: The effect of an attractive interaction

We present a model for the effect of an attractive interaction between dislocations and hard spherical particles on the process of dislocation bypass by local climb. The interaction is treated by assigning a line tension to the dislocation which is lower in the vicinity of the particle than in the matrix. We find that even for very modest interactions, the strongest barrier to dislocation bypass is no longer provided by the climb obstacle, but rather by the detachment of the dislocation from the particle after climb over the particle is complete. The model provides a possible explanation for some experimentally observed dislocation configurations in crept ODS superalloys and for the creep thresholds which are typical of such alloys.