Prefrontal-enriched SLIT1 expression in Old World monkey cortex established during the postnatal development.

To elucidate the molecular basis of the specialization of cortical architectures, we searched for genes differentially expressed among neocortical areas of Old World monkeys by restriction landmark cDNA scanning . We found that mRNA of SLIT1, an axon guidance molecule, was enriched in the prefrontal cortex but with developmentally related changes. In situ hybridization analysis revealed that SLIT1 mRNA was mainly distributed in the middle layers of most cortical areas, robustly in the prefrontal cortex and faintly in primary sensory areas. The lowest expression was in the primary visual area. Analyses of other SLIT (SLIT2 and SLIT3) mRNAs showed preferential expression in the prefrontal cortex with a distinct laminar pattern. By contrast, the receptor Roundabout (ROBO1 and ROBO2) mRNAs were widely distributed throughout the cortex. Perinatally, SLIT1 mRNA was abundantly expressed in the cortex with modest area specificity. Downregulation of expression initially occurred in early sensory areas around postnatal day 60 and followed in the association areas. The prefrontal area-enriched SLIT1 mRNA expression results from a relatively greater attenuation of this expression in the other areas. These results suggest that its role is altered postnatally and that this is particularly important for prefrontal connectivity in the Old World monkey cortex.

Molecular-dynamics simulation of crystallization in helical polymers.

The molecular mechanism of crystallization in helical polymers is a fascinating but very difficult subject of research. We here report our recent efforts toward better understanding of the crystallization in helical polymers by use of molecular-dynamics simulation. With straightforward approaches to the problem being quite difficult, we adopt a different strategy of categorizing the helical polymers into two distinct types: one type is a simple bare helix which is essentially made of backbone atomic groups only and has smoother molecular contours, and the other is a more general helix having large side groups that would considerably hamper molecular motion and crystallization. Both types of helical polymers are here constructed by use of the united atom model, but they show quite distinct crystallization behavior; the crystallization of the former-type polymer is rather fast, while that of the latter-type polymer is extremely slow. We find that the bare helix, when rapidly cooled in free three-dimensional space, freezes into partially ordered state with limited intramolecular and intermolecular orders, and that remarkable improvement of order and growth of an ordered chain-folded crystallite occurs by very long-time annealing of the partially ordered state around the apparent freezing temperature. We also study crystallization of the bare helix upon a growth surface; the crystallization in this case proceeds much faster through highly cooperative process of the intermolecular and the intramolecular degrees of freedom. On the other hand, crystallization of the realistic model of isotactic polypropylene (iPP) having pendant methylene groups is found to be extremely sluggish. By restricting the spatial dimension of the system thereby fully disentangling the chain, we observe that the molecule of iPP crystallizes very quickly onto the crystal substrate made of the same iPP chain. Quite remarkable is that the molecule of iPP strictly recognizes the helical sense of the substrate chain and efficiently selects its chirality during crystallization.

Molecular dynamics modeling of polymer crystallization; from simple polymers to helical ones.

Crystallization of helical polymers is a very big challenge for molecular simulation. It involves many significant issues, such as folding in biomolecules and molecular recognition during crystal growth. Though direct molecular simulations of the process still involve very difficult problems, we here report our recent efforts toward better understanding of the crystallization in helical polymers. We begin with a brief review of our former studies on simple polyethylene-like polymers, and then we introduce several helical polymer models which are systematically made more complicated. We have already reported that a simple polyethylene-like polymer crystallizes very fast into chain folded lamellae from the melt. A slight modification of this simple polymer model by introducing proper bond angle and dihedral angle potentials gives one of the present models of the helical polymer. This helical polymer model is devised to be relatively rigid but mobile, to show easy helix-reversals, and to have a definite preference for gauche bonds. We find that this highly mobile helical polymer shows quick chain folded crystallization and forms approximate 4/1 helical structure. The intra- and the intermolecular order grow quite simultaneously suggesting highly cooperative nature of the phenomena. Further elaboration of the helical model, giving pendant side groups and higher energy barrier to the helix reversals, leads us to a realistic united atom model of iPP. The conventional and the multi-canonical Monte Carlo simulations are applied to find probable modes of chain folding and the ground state conformations. Though a very short chain readily forms a regular 3/1 helix of alternating trans and gauche bonds, much longer chains of 30- and 50-propylene units are not found to have energetic ground states in the regularly folded conformations.