DCC plays a role in navigation of forebrain axons across the ventral midbrain commissure in embryonic Xenopus

In the developing vertebrate brain, growing axons establish a scaffold of axon tracts connected across the midline via commissures. We have previously identified a population of telencephalic neurons that express NOC-2, a novel glycoform of the neural cell adhesion molecule N-CAM that is involved in axon guidance in the forebrain. These axons arise from the presumptive telencephalic nucleus, course caudally along the principal longitudinal tract of the forebrain, cross the ventral midline in the midbrain, and then project to the contralateral side of the brain. In the present study we have investigated mechanisms controlling the growth of these axons across the ventral midline of the midbrain. The axon guidance receptor DCC is expressed by the NOC-2 population of axons both within the longitudinal tract and within the ventral midbrain commissure. Disruption of DCC-dependent interactions, both in vitro and in vivo, inhibited the NOC-2 axons from crossing the ventral midbrain. Instead, these axons grew along aberrant trajectories away from the midline, suggesting that DCC-dependent interactions are important for overcoming inhibitory mechanisms within the midbrain of the embryonic vertebrate brain. Thus, coordinated responsiveness of forebrain axons to both chemostimulatory and chemorepulsive cues appears to determine whether they cross the ventral midline in the midbrain, (C) 2000 Academic Press.

Epidemiological modelling (including economic modelling) and its role in preventive drug therapy

In contrast to curative therapies, preventive therapies are administered to largely healthy individuals over long periods. The risk-benefit and cost-benefit ratios are more likely to be unfavourable, making treatment decisions difficult. Drug trials provide insufficient information for treatment decisions, as they are conducted on highly selected populations over short durations, estimate only relative benefits of treatment and offer little information on risks and costs. Epidemiological modelling is a method of combining evidence from observational epidemiology and clinical trials to assist in clinical and health policy decision-making. It can estimate absolute benefits, risks and costs of long-term preventive strategies, and thus allow their precise targeting to individuals for whom they are safest and most cost-effective. Epidemiological modelling also allows explicit information about risks and benefits of therapy to be presented to patients, facilitating informed decision-making.

Tomosyn interacts with the t-SNAREs Syntaxin4 and SNAP23 and plays a role in insulin-stimulated GLUT4 translocation

The Sec1p-like/Munc18 (SM) protein Munc18a binds to the neuronal t-SNARE Syntaxin1A and inhibits SNARE complex assembly. Tomosyn, a cytosolic Syntaxin1A-binding protein, is thought to regulate the interaction between Syntaxin1A and Munc18a, thus acting as a positive regulator of SNARE assembly. In the present study we have investigated the interaction between b-Tomosyn and the adipocyte SNARE complex involving Syntaxin4/SNAP23/VAMP-2 and the SM protein Munc18c, in vitro, and the potential involvement of Tomosyn in regulating the translocation of GLUT4 containing vesicles, in vivo. Tomosyn formed a high affinity ternary complex with Syntaxin4 and SNAP23 that was competitively inhibited by VAMP-2. Using a yeast two-hybrid assay we demonstrate that the VAMP-2-like domain in Tomosyn facilitates the interaction with Syntaxin4. Overexpression of Tomosyn in 3T3-L1 adipocytes inhibited the translocation of green fluorescent protein-GLUT4 to the plasma membrane. The SM protein Munc18c was shown to interact with the Syntaxin4 monomer, Syntaxin4 containing SNARE complexes, and the Syntaxin4/Tomosyn complex. These data suggest that Tomosyn and Munc18c operate at a similar stage of the Syntaxin4 SNARE assembly cycle, which likely primes Syntaxin4 for entry into the ternary SNARE complex.

Polarization vision and its role in biological signaling

Visual pigments, the molecules in photoreceptors that initiate the process of vision, are inherently dichroic, differentially absorbing light according to its axis of polarization. Many animals have taken advantage of this property to build receptor systems capable of analyzing the polarization of incoming light, as polarized light is abundant in natural scenes (commonly being produced by scattering or reflection). Such polarization sensitivity has long been associated with behavioral tasks like orientation or navigation. However, only recently have we become aware that it can be incorporated into a high-level visual perception akin to color vision, permitting segmentation of a viewed scene into regions that differ in their polarization. By analogy to color vision, we call this capacity polarization vision. It is apparently used for tasks like those that color vision specializes in: contrast enhancement, camouflage breaking, object recognition, and signal detection and discrimination. While color is very useful in terrestrial or shallow-water environments, it is an unreliable cue deeper in water due to the spectral modification of light as it travels through water of various depths or of varying optical quality. Here, polarization vision has special utility and consequently has evolved in numerous marine species, as well as at least one terrestrial animal. In this review, we consider recent findings concerning polarization vision and its significance in biological signaling.

Competing notions of social justice and contradictions in special education reform

In the past three decades, special education has been subjected to extensive critique and reform of practices. These critiques have been based on notions of social justice and equity. However, the field has suffered from inadequate attention to assumptions about social justice. Social justice is essentially a contested concept. Rather than representing a unitary and universally shared concept, social justice has variable meanings. Differing views of social justice can be seen to underlie apparent contradictions in continuing practice in response to pressures for reform. Reforms predicated on individual rights have been undermined by deep commitments to meritocratic practices in U.S. schools. Reforms based on more communitarian principles, however, ignore the need for structure and the tendency for communal values to marginalize people with disabilities. Special education reform today requires a different basis in a relational definition of the self, structures to support the qualities of relationships, and a belief in the mutability of social justice.