We explore the relative utility of shape from shading and binocular disparity for depth perception. Ray-traced images either featured a smooth surface illuminated from above (shading-only) or were defined by small dots (disparity-only). Observers judged which of a pair of smoothly curved convex objects had most depth. The shading cue was around half as reliable as the rich disparity information for depth discrimination. Shading- and disparity-defined cues where combined by placing dots in the stimulus image, superimposed upon the shaded surface, resulting in veridical shading and binocular disparity. Independently varying the depth delivered by each channel allowed creation of conflicting disparity-defined and shading-defined depth. We manipulated the reliability of the disparity information by adding disparity noise. As noise levels in the disparity channel were increased, perceived depths and variances shifted toward those of the now more reliable shading cue. Several different models of cue combination were applied to the data. Perceived depths and variances were well predicted by a classic maximum likelihood estimator (MLE) model of cue integration, for all but one observer. We discuss the extent to which MLE is the most parsimonious model to account for observer performance.

Recent studies have revealed extensive cortical demyelination in patients with progressive multiple sclerosis (MS). Demyelination in gray matter lesions is associated with activation of microglia. Macrophages and microglia are known to express myeloperoxidase (MPO) and generate reactive oxygen species during myelin phagocytosis in the white matter. In the present study we examined the extent of microglial activation in the cerebral cortex and the relationship of microglial activation and MPO activity to cortical demyelination. Twenty-one cases of neuropathologically confirmed multiple sclerosis, with 34 cortical lesions, were used to assess microglial activation. HLA-DR immunolabeling of activated microglia was significantly higher in demyelinated MS cortex than control cortex and, within the MS cohort, was significantly greater within cortical lesions than in matched non-demyelinated areas of cortex. In homogenates of MS cortex, cortical demyelination was associated with significantly elevated MPO activity. Immunohistochemistry revealed MPO in CD68-positive microglia within cortical plaques, particularly toward the edge of the plaques, but not in microglia in adjacent non-demyelinated cortex. Cortical demyelination in MS is associated with increased activity of MPO, which is expressed by a CD68-positive subset of activated microglia, suggesting that microglial production of reactive oxygen species is likely to be involved in cortical demyelination.

The luminance and colour gradients across an image are the result of complex interactions between object shape, material and illumination. Using such variations to infer object shape or surface colour is therefore a difficult problem for the visual system. We know that changes to the shape of an object can affect its perceived colour, and that shading gradients confer a sense of shape. Here we investigate if the visual system is able to effectively utilise these gradients as a cue to shape perception, even when additional cues are not available. We tested shape perception of a folded card object that contained illumination gradients in the form of shading and more subtle effects such as inter-reflections. Our results suggest that observers are able to use the gradients to make consistent shape judgements. In order to do this, observers must be given the opportunity to learn suitable assumptions about the lighting and scene. Using a variety of different training conditions, we demonstrate that learning can occur quickly and requires only coarse information. We also establish that learning does not deliver a trivial mapping between gradient and shape; rather learning leads to the acquisition of assumptions about lighting and scene parameters that subsequently allow for gradients to be used as a shape cue. The perceived shape is shown to be consistent for convex and concave versions of the object that exhibit very different shading, and also similar to that delivered by outline, a largely unrelated cue to shape. Overall our results indicate that, although gradients are less reliable than some other cues, the relationship between gradients and shape can be quickly assessed and the gradients therefore used effectively as a visual shape cue.

The task of deciding how long sensory events seem to last is one that the human nervous system appears to perform rapidly and, for sub-second intervals, seemingly without conscious effort. That these estimates can be performed within and between multiple sensory and motor domains suggest time perception forms one of the core, fundamental processes of our perception of the world around us. Given this significance, the current paucity in our understanding of how this process operates is surprising. One candidate mechanism for duration perception posits that duration may be mediated via a system of duration-selective 'channels', which are differentially activated depending on the match between afferent duration information and the channels' 'preferred' duration. However, this model awaits experimental validation. In the current study, we use the technique of sensory adaptation, and we present data that are well described by banks of duration channels that are limited in their bandwidth, sensory-specific, and appear to operate at a relatively early stage of visual and auditory sensory processing. Our results suggest that many of the computational principles the nervous system applies to coding visual spatial and auditory spectral information are common to its processing of temporal extent.

BACKGROUND: Alopecia causes widespread psychological distress, but is relatively poorly controlled. The development of new treatments is hampered by the lack of suitable human hair follicle models. Although intermediate and vellus hair follicles are the main clinical targets for pharmacological therapy, terminal hair follicles are more frequently studied as smaller hair follicles are more difficult to obtain. OBJECTIVES: This investigation was designed to quantify in vivo morphological and in vitro behavioural differences in organ culture between matched intermediate and terminal hair follicles, in order to develop a new clinically relevant model system. METHODS: Microdissected terminal and intermediate hair follicles, from the same individuals, were analysed morphometrically (250 follicles; five individuals), or observed and measured over 9 days of organ culture (210 follicles; six individuals). RESULTS: Intermediate hair follicles were less pigmented and smaller, penetrating less below the skin surface (mean +/- SEM) (2.59 +/- 0.07 vs. 3.52 +/- 0.10 mm; P = 0.02), with smaller fibre (0.03 +/- 0.002 vs. 0.07 +/- 0.002 mm), connective tissue sheath (0.24 +/- 0.01 mm vs. 0.33 +/- 0.01 mm), bulb (0.19 +/- 0.01 vs. 0.31 +/- 0.01 mm) and dermal papilla (0.06 +/- 0.002 vs. 0.12 +/- 0.01 mm) diameters (P < 0.001). Intermediate hair follicle bulbs appeared 'tubular', unlike their 'bulbous' terminal follicle counterparts. In organ culture they also grew more slowly (0.044 +/- 0.002 vs. 0.067 +/- 0.003 mm per day; P < 0.001), remained in anagen longer (84 +/- 0.03% vs. 74 +/- 0.03% at day 9; P = 0.012) and produced less hair fibre (0.36 +/- 0.02 vs. 0.50 +/- 0.03 mm; P < 0.001) than terminal follicles. CONCLUSIONS: Smaller intermediate hair follicles showed major morphological differences from terminal follicles in vivo and retained significant, biologically relevant differences in vitro in organ culture. Therefore, intermediate hair follicles offer a novel, exciting, more clinically relevant, albeit technically difficult, model for future investigations into hair growth. This should be particularly important for developing new therapies.

Area V3A was identified in five human subjects on both a functional and retinotopic basis using functional magnetic resonance imaging techniques. V3A, along with other visual areas responsive to motion, was then targeted for disruption by repetitive transcranial magnetic stimulation (rTMS) whilst the participants performed a delayed speed matching task. The stimuli used for this task included chromatic, isoluminant motion stimuli that activated either the L-M or S-(L+M) cone-opponent mechanisms, in addition to moving stimuli that contained only luminance contrast (L+M). The speed matching task was performed for chromatic and luminance stimuli that moved at slow (2 degrees/s) or faster (8 degrees/s) speeds. The application of rTMS to area V3A produced a perceived slowing of all chromatic and luminance stimuli at both slow and fast speeds. Similar deficits were found when rTMS was applied to V5/MT+. No deficits in performance were found when areas V3B and V3d were targeted by rTMS. These results provide evidence of a causal link between neural activity in human area V3A and the perception of chromatic isoluminant motion. They establish area V3A, alongside V5/MT+, as a key area in a cortical network that underpins the analysis of not only luminance but also chromatically-defined motion.

The parallel processing of information forms an important organisational principle of the primate visual system. Here we describe experiments which use a novel chromatic-achromatic temporal compound stimulus to simultaneously identify colour and luminance specific signals in the human electroretinogram (ERG). Luminance and chromatic components are separated in the stimulus; the luminance modulation has twice the temporal frequency of the chromatic modulation. ERGs were recorded from four trichromatic and two dichromatic subjects (1 deuteranope and 1 protanope). At isoluminance, the fundamental (first harmonic) response was elicited by the chromatic component in the stimulus. The trichromatic ERGs possessed low-pass temporal tuning characteristics, reflecting the activity of parvocellular post-receptoral mechanisms. There was very little first harmonic response in the dichromats' ERGs. The second harmonic response was elicited by the luminance modulation in the compound stimulus and showed, in all subjects, band-pass temporal tuning characteristic of magnocellular activity. Thus it is possible to concurrently elicit ERG responses from the human retina which reflect processing in both chromatic and luminance pathways. As well as providing a clear demonstration of the parallel nature of chromatic and luminance processing in the human retina, the differences that exist between ERGs from trichromatic and dichromatic subjects point to the existence of interactions between afferent post-receptoral pathways that are in operation from the earliest stages of visual processing.

The relevance of preconceptional and prenatal toxicant exposures for genomic stability in offspring is difficult to analyze in human populations, because gestational exposures usually cannot be separated from preconceptional exposures. To analyze the roles of exposures during gestation and conception on genomic stability in the offspring, stability was assessed via the Comet assay and highly sensitive, semiautomated confocal laser scans of gammaH2AX foci in cord, maternal, and paternal blood as well as spermatozoa from 39 families in Crete, Greece, and the United Kingdom. With use of multivariate linear regression analysis with backward selection, preconceptional paternal smoking (% tail DNA: P>0.032; gammaH2AX foci: P>0.018) and gestational maternal (% tail DNA: P>0.033) smoking were found to statistically significantly predict DNA damage in the cord blood of F1 offspring. Maternal passive smoke exposure was not identified as a predictor of DNA damage in cord blood, indicating that the effect of paternal smoking may be transmitted via the spermatozoal genome. Taken together, these studies reveal a role for cigarette smoke in the induction of DNA alterations in human F1 offspring via exposures of the fetus in utero or the paternal germline. Moreover, the identification of transgenerational DNA alterations in the unexposed F1 offspring of smoking-exposed fathers supports the claim that cigarette smoke is a human germ cell mutagen.

Several lines of evidence support an autoimmune basis for alopecia areata (AA), a common putative autoimmune hair loss disorder. However, definitive support is lacking largely because the identity of hair follicle (HF) autoantigen(s) involved in its pathogenesis remains unknown. Here, we isolated AA-reactive HF-specific antigens from normal human scalp anagen HF extracts by immunoprecipitation using serum antibodies from 10 AA patients. Samples were analyzed by LC-MALDI-TOF/TOF mass spectrometry, which indicated strong reactivity to the hair growth phase-specific structural protein trichohyalin in all AA sera. Keratin 16 (K16) was also identified as another potential AA-relevant target HF antigen. Double immunofluorescence studies using AA (and control sera) together with a monoclonal antibody to trichohyalin revealed that AA sera contained immunoreactivity that colocalized with trichohyalin in the growth phase-specific inner root sheath of HF. Furthermore, a partial colocalization of AA serum reactivity with anti-K16 antibody was observed in the outer root sheath of the HF. In summary, this study supports the involvement of an immune response to anagen-specific HFs antigens in AA and specifically suggests that an immune response to trichohyalin and K16 may have a role in the pathogenesis of the enigmatic disorder.

Bone morphogenetic proteins (BMPs) play pivotal roles in the regulation of skin development. To study the role of BMPs in skin tumorigenesis, BMP antagonist noggin was used to generate keratin 14-targeted transgenic mice. In contrast to wild-type mice, transgenic mice developed spontaneous hair follicle-derived tumors, which resemble human trichofolliculoma. Global gene expression profiles revealed that in contrast to anagen hair follicles of wild-type mice, tumors of transgenic mice showed stage-dependent increases in the expression of genes encoding the selected components of Wnt and Shh pathways. Specifically, expression of the Wnt ligands increased at the initiation stage of tumor formation, whereas expression of the Wnt antagonist and tumor suppressor Wnt inhibitory factor-1 decreased, as compared with fully developed tumors. In contrast, expression of the components of Shh pathway increased in fully developed tumors, as compared with the tumor placodes. Consistent with the expression data, pharmacological treatment of transgenic mice with Wnt and Shh antagonists resulted in the stage-dependent inhibition of tumor initiation, and progression, respectively. Furthermore, BMP signaling stimulated Wnt inhibitory factor-1 expression and promoter activity in cultured tumor cells and HaCaT keratinocytes, as well as inhibited Shh expression, as compared with the corresponding controls. Thus, tumor suppressor activity of the BMPs in skin epithelium depends on the local concentrations of noggin and is mediated at least in part via stage-dependent antagonizing of Wnt and Shh signaling pathways.