A comparative analysis of vertical and horizontal fixation disparity in sentence reading.

Humans have two, frontally placed eyes and during reading oculomotor and sensory processes are needed to combine the two inputs into a unified percept of the text. Generally, slight vergence errors, i.e., fixation disparities, occur but do not cause double vision since disparate retinal inputs fall into Panum's fusional area, that is, a range of disparity wherein sensory fusion of the two retinal images is achieved. In this study, we report benchmark data with respect to the mean magnitude and range of vertical compared to horizontal fixation disparities for natural reading. Our data clearly fit to an elliptical pattern of Panum's fusional area that corresponds with theoretical estimates. Furthermore, when we examined disparity-driven vergence adjustments during fixations by comparing monocular with binocular reading conditions, we found that only horizontal fixation disparities increased significantly under conditions of monocular stimulation. Also, no significant vertical fine-tuning (vergence adjustment) was observed for vergence eye movements during reading fixations. Thus, horizontal and vertical fixation disparities and vergence adjustments during reading showed quite different characteristics, and this dissociation is directly related to the functional role of vergence adjustments: vertical fusion - and vertical vergence - subserve the maintenance of a single percept and stereopsis by keeping the eyes in register and allowing for horizontal fusional processes to successfully operate over a vertically aligned input. A reliable and stable vertical alignment is, thus, a pre-requisite over which horizontal fusional responses (and depth perception) can work most efficiently - even in a task like reading.

Vergence responses to vertical binocular disparity during lexical identification.

Humans typically make use of both eyes during reading, which necessitates precise binocular coordination in order to achieve a unified perceptual representation of written text. A number of studies have explored the magnitude and effects of naturally occurring and induced horizontal fixation disparity during reading and non-reading tasks. However, the literature concerning the processing of disparities in different dimensions, particularly in the context of reading, is considerably limited. We therefore investigated vertical vergence in response to stereoscopically presented linguistic stimuli with varying levels of vertical offset. A lexical decision task was used to explore the ability of participants to fuse binocular image disparity in the vertical direction during word identification. Additionally, a lexical frequency manipulation explored the potential interplay between visual fusion processes and linguistic processes. Results indicated that no significant motor fusional responses were made in the vertical dimension (all p-values>.11), though that did not hinder successful lexical identification. In contrast, horizontal vergence movements were consistently observed on all fixations in the absence of a horizontal disparity manipulation. These findings add to the growing understanding of binocularity and its role in written language processing, and fit neatly with previous literature regarding binocular coordination in non-reading tasks.

Analyzing the pupil response due to increased cognitive demand: an independent component analysis study.

Pupillometry is used to indicate the relative extent of processing demands within or between tasks; however, this analysis is complicated by the fact that the pupil also responds to low-level aspects of visual input. First, we attempted to identify "principal" components that contribute to the pupil response by computing a principal component analysis (PCA) and second, to reveal "hidden" sources within the pupil response by calculating an independent component analysis (ICA). Pupil response data were collected while subjects read, added or multiplied numbers. A set of 3 factors/components were identified as resembling the individual pupil responses, but only one ICA component changed in concordance to the cognitive demand. This component alone accounted for about 50% of the variance of the pupil response during the most demanding task, i.e. the multiplication task. The highest impact of this factor was observed for 2000 to 300ms after task onset. Even though we did not attempt to answer the question of the functional background of the components 1 and 3, we speculated that component 2 might reflect the effort a subject engages to perform a task with greater difficulty.

Accommodation modulates the individual difference between objective and subjective measures of the final convergence step response.

Measuring vergence eye movements with dichoptic nonius lines (subjectively) usually leads to an overestimation of the vergence state after a step response: a subjective vergence overestimation (SVO). We tried to reduce this SVO by presenting a vergence stimulus that decoupled vergence and accommodation during the step response, i.e. reduced the degree of 'forced vergence'. In a mirror-stereoscope, we estimated convergence step responses with nonius lines presented at 1000 ms after a disparity step-stimulus and compared it to objective recordings (EyeLink II; n = 6). We presented a vertical line, a cross/rectangle stimulus and a difference-of-gaussians (DOG) pattern. For 180 min arc step stimuli, the subjective measures revealed a larger final vergence response than the objective measure; for the vertical line this SVO was 20 min arc, while it was significantly smaller for the DOG (12 min arc). For 60 min arc step-responses, no overestimation was observed. Additionally, we measured accommodation, which changed more for the DOG-pattern compared with the line-stimulus; this relative increase correlated with the corresponding relative change of SVO (r = 0.77). Both findings (i.e. no overestimation for small steps and a weaker one for the DOG-pattern) reflect lesser conflicting demand on accommodation and vergence under 'forced-vergence' viewing; consequently, sensory compensation is reduced and subjective and objective measures of vergence step responses tend to agree.

Objective and subjective measures of vergence step responses.

Dichoptic nonius lines are used for subjectively (psychophysically) measuring vergence states, but they have been questioned as valid indicators of vergence eye position. In a mirror-stereoscope, we presented convergent and divergent step-stimuli and estimated the vergence response with nonius lines flashed at fixed delays after the disparity step stimulus. For each delay, an adaptive psychophysical procedure was run to determine the physical nonius offset required for subjective alignment; these vergence states were compared with objective eye movement recordings. Between both measures of initial vergence, we calculated the maximal cross-correlation coefficient: the median in our sample was about 0.9 for convergence and divergence, suggesting a good agreement. Relative to the objective measures, the subjective method revealed a smaller vergence velocity and a larger vergence response in the final phase of the response, but both measures were well correlated. The dynamic nonius test is therefore considered to be useful to relatively evaluate a subject's ability in disparity vergence.

[Autoantigens of subepidermal bullous autoimmune dermatoses]. / Autoantigene subepidermal Blasen bildender Autoimmundermatosen.

The dermal-epidermal junction contains a network of structural proteins that link epidermis and dermis. A central component of this complex is the cell membrane-associated hemidesmosomal plaque. Formation of autoantibodies against different components of this hemidesmosomal anchoring complex can lead to subepidermal blisters. Such autoantibodies have been frequently used to characterize the target antigens at the molecular level. Autoimmune subepidermal blistering diseases include bullous pemphigoid, pemphigoid gestationis, lichen planus pemphigoides, linear IgA disease, cicatricial pemphigoid, anti-p450-, anti-p200- and anti-p105-pemphigoid, epidermolysis bullosa acquisita, bullous systemic lupus erythematosus and dermatitis herpetiformis Duhring. Differences in the clinical picture of these diseases can be attributed, at least in part, to the different specificity of the autoantibodies involved. The autoimmune response is further modulated by inflammatory cells and other inflammatory mediators. Native and recombinant forms of the autoantigens are increasingly used for the diagnosis of these diseases.

Remodeling of vimentin cytoskeleton correlates with enhanced motility of promyelocytic leukemia cells during differentiation induced by retinoic acid.

The intermediate filament (IFs) cytoskeleton is one of the major determinants for the mechanical properties of cytoplasm. Vimentin is the major IFs protein in peripheral blood neutrophils. We investigated its expression and function during neutrophil differentiation using the promyelocytic leukemia cell line NB4. The differentiation of NB4 cells along the neutrophil lineage and the monocytic pathway was induced by all-trans retinoic acid (ATRA) and phorbol esters (PMA), respectively. We demonstrated a down-regulation of vimentin after ATRA treatment of NB4 cells by immunoblotting and immunofluorescence. The architecture of the vimentin cytoskeleton in differentiated NB4 cells resembled that observed in mature neutrophils. In contrast, we showed a slight increase of vimentin content in phorbol ester (PMA)-treated NB4 cells. The structural features of the vimentin cytoskeleton obtained by image analysis showed significant differences in network density and directionality between ATRA-treated NB4 cells and controls. The functional consequence of the cytoskeletal remodeling for the mechanical properties of NB4 cells was assessed in migration assays. After ATRA treatment, we found a 4-fold increased migration of NB4 cells across transwell membranes with a 8 microm pore size without any cell size modification. No significant differences between PMA-treated NB4 cells and control cells could be observed using similar tests. These results indicate that both vimentin expression and network architecture are tightly controlled during neutrophil differentiation to regulate the mechanical properties of these cells.

Autoantibodies to BP180 associated with bullous pemphigoid release interleukin-6 and interleukin-8 from cultured human keratinocytes.

Bullous pemphigoid is an inflammatory subepidermal blistering disease that is associated with auto- antibodies to the keratinocyte surface protein, BP180. In addition to the binding of autoantibodies, the infiltration of inflammatory cells is necessary for blister formation. Cytokines, including interleukin-6 and interleukin-8, have been implicated in the disease process of both human and experimental murine bullous pemphigoid. This study was aimed at testing the hypothesis that the binding of anti-BP180 antibodies to their target antigen triggers a signal transduction event that results in the secretion of these pro-inflammatory cytokines. Consistent with this hypothesis, treatment of cultured normal human epidermal keratinocytes with bullous pemphigoid IgG, but not control IgG, led to increased levels of interleukin-6 and interleukin-8, but not interleukin-1alpha, interleukin-1beta, tumor necrosis factor-alpha, interleukin-10, or monocyte chemoattractant protein-1, in the culture medium. This effect was concentration- and time-dependent and was abolished by depleting the bullous pemphigoid IgG of reactivity to two distinct epitopes on the BP180 NC16A domain. Upregulation of interleukin-6 and interleukin-8 was found at both protein and mRNA levels. In addition, bullous pemphigoid IgG did not induce the release of interleukin-6 and interleukin-8 from BP180-deficient keratinocytes obtained from a patient with generalized atrophic benign epidermolysis bullosa. These data indicate that bullous pemphigoid-associated autoantibodies to the human BP180 ectodomain trigger a signal transducing event that leads to expression and secretion of interleukin-6 and interleukin-8 from human keratinocytes.

Sex determination in Ellobius lutescens: the story of an enigma.

The unusual karyotype of Ellobius lutescens (2n = 17,X in males and females) has attracted permanent interest and prompted a series of hypotheses on sex determination in this species since its first description by Matthey (1953). The developing knowledge about the sex chromosomes and sex determination as well as the availability of new cytogenetic and molecular genetic techniques prompted studies to test the compatibility between current hypotheses and new findings and rendered modifications of the hypotheses necessary. After a long period dominated by the question what the sex chromosome constitution of this species might be and where the testis determining factor could be located, the presence of Sry had been eventually excluded and sex determination attributed to a hypothetical mutated gene acting downstream of Sry. An X-chromosomal or autosomal location of this gene can be assessed by cosegregation of sex with X-chromosome markers. Some preliminary results concerning X-chromosome dinucleotide repeat markers are reported. However, these markers were homomorphic in Ellobius lutescens. We now report evidence that Zfy is also missing in Ellobius lutescens and E. tancrei (males and females XX), a finding from which we conclude that the entire Y chromosome has been lost from these species. Perspectives concerning future studies are discussed.