Differential methylation of the TRPA1 promoter in pain sensitivity.

Chronic pain is a global public health problem, but the underlying molecular mechanisms are not fully understood. Here we examine genome-wide DNA methylation, first in 50 identical twins discordant for heat pain sensitivity and then in 50 further unrelated individuals. Whole-blood DNA methylation was characterized at 5.2 million loci by MeDIP sequencing and assessed longitudinally to identify differentially methylated regions associated with high or low pain sensitivity (pain DMRs). Nine meta-analysis pain DMRs show robust evidence for association (false discovery rate 5%) with the strongest signal in the pain gene TRPA1 (P=1.2 × 10(-13)). Several pain DMRs show longitudinal stability consistent with susceptibility effects, have similar methylation levels in the brain and altered expression in the skin. Our approach identifies epigenetic changes in both novel and established candidate genes that provide molecular insights into pain and may generalize to other complex traits.

Hierarchical classification of G-protein-coupled receptors with data-driven selection of attributes and classifiers.

We address the important bioinformatics problem of predicting protein function from a protein's primary sequence. We consider the functional classification of G-Protein-Coupled Receptors (GPCRs), whose functions are specified in a class hierarchy. We tackle this task using a novel top-down hierarchical classification system where, for each node in the class hierarchy, the predictor attributes to be used in that node and the classifier to be applied to the selected attributes are chosen in a data-driven manner. Compared with a previous hierarchical classification system selecting classifiers only, our new system significantly reduced processing time without significantly sacrificing predictive accuracy.

Interaction of visual and tactile information in the control of chicks' locomotion in the visual cliff.

The behaviour of two-day-old chicks placed on the deep side of a visual cliff was examined. With increasing depth of the floor below the chicks, latency to move over the deep side towards another chick on the shallow side increased, while speed of locomotion decreased. Chicks given the same incentive to step over a visible edge onto the deep side showed a stronger inhibition of movement at all depths, indicating that absolute depth of a surface and relative depth of an edge affect behaviour differently. At depths greater than 4 cm, the majority of chicks performed a jump from the deep to the shallow side, and the distances over which they jumped corresponded to those jumped when tested with a real gap. These results suggest that detection of the far side of a gap alone is sufficient to elicit a jump. Just before jumping, chicks adopted a head orientation which depended on the vertical distance of the cliff edge below them. Changes in head orientation did not maintain retinal fixation of the edge, and may instead be important in setting the correct direction of thrust when jumping.

Head orientation in pigeons during landing flight.

Landing flights of pigeons were video recorded or filmed, and frame-by-frame measurements were made of the angle of the head relative to the horizontal, and of the position of the perch in the visual field. The angle of the head increases above that seen in free flight, to a value which is correlated with the trajectory of approach to the perch. As a result, the perch is fixated 20-25 degrees above the beak early in landing flight. The possible significance of the behaviour is discussed in relation to specialised retinal areas and to lower-field myopia.

Visual head extension: transitional head coordination in the pigeon squab (Columbia livia).

We describe a previously unreported visuomotor behavior of the developing pigeon squab, which we term "visual head extension." The behavior consists of extension and lowering of the head as the bird descends towards a surface or experiences the optical equivalent of such a descent. A peak in performance occurs 10 days after hatching. Evidence obtained shows that both vestibular and dynamic visual information can independently produce head extension. We go on to place the new behavioral response in the context of a dynamic, relational approach to perceptuomotor coordination, and outline the corresponding advantages of studying the single-limb, head-neck system in the pigeon.