Analysis of tissue transglutaminase function in the migration of Swiss 3T3 fibroblasts:the active-state conformation of the enzyme does not affect cell motility but is important for its secretion

Increasing evidence suggests that tissue transglutaminase (tTGase; type II) is externalized from cells, where it may play a key role in cell attachment and spreading and in the stabilization of the extracellular matrix (ECM) through protein cross-linking. However, the relationship between these different functions and the enzyme's mechanism of secretion is not fully understood. We have investigated the role of tTGase in cell migration using two stably transfected fibroblast cell lines in which expression of tTGase in its active and inactive (C277S mutant) states is inducible through the tetracycline-regulated system. Cells overexpressing both forms of tTGase showed increased cell attachment and decreased cell migration on fibronectin. Both forms of the enzyme could be detected on the cell surface, but only the clone overexpressing catalytically active tTGase deposited the enzyme into the ECM and cell growth medium. Cells overexpressing the inactive form of tTGase did not deposit the enzyme into the ECM or secrete it into the cell culture medium. Similar results were obtained when cells were transfected with tTGase mutated at Tyr(274) (Y274A), the proposed site for the cis,trans peptide bond, suggesting that tTGase activity and/or its tertiary conformation dependent on this bond may be essential for its externalization mechanism. These results indicate that tTGase regulates cell motility as a novel cell-surface adhesion protein rather than as a matrix-cross-linking enzyme. They also provide further important insights into the mechanism of externalization of the enzyme into the extracellular matrix.

Contrast summation across eyes and space is revealed along the entire dipper function by a "Swiss cheese" stimulus.

Previous contrast discrimination experiments have shown that luminance contrast is summed across ocular (T. S. Meese, M. A. Georgeson, & D. H. Baker, 2006) and spatial (T. S. Meese & R. J. Summers, 2007) dimensions at threshold and above. However, is this process sufficiently general to operate across the conjunction of eyes and space? Here we used a "Swiss cheese" stimulus where the blurred "holes" in sine-wave carriers were of equal area to the blurred target ("cheese") regions. The locations of the target regions in the monocular image pairs were interdigitated across eyes such that their binocular sum was a uniform grating. When pedestal contrasts were above threshold, the monocular neural images contained strong evidence that the high-contrast regions in the two eyes did not overlap. Nevertheless, sensitivity to dual contrast increments (i.e., to contrast increments in different locations in the two eyes) was a factor of ∼1.7 greater than to single increments (i.e., increments in a single eye), comparable with conventional binocular summation. This provides evidence for a contiguous area summation process that operates at all contrasts and is influenced little, if at all, by eye of origin. A three-stage model of contrast gain control fitted the results and possessed the properties of ocularity invariance and area invariance owing to its cascade of normalization stages. The implications for a population code for pattern size are discussed.

Body iron is associated with cognitive executive planning function in college women

Evidence of the relationship between altered cognitive function and depleted Fe status is accumulating in women of reproductive age but the degree of Fe deficiency associated with negative neuropsychological outcomes needs to be delineated. Data are limited regarding this relationship in university women in whom optimal cognitive function is critical to academic success. The aim of the present study was to examine the relationship between body Fe, in the absence of Fe-deficiency anaemia, and neuropsychological function in young college women. Healthy, non-Anaemic undergraduate women (n 42) provided a blood sample and completed a standardised cognitive test battery consisting of one manual (Tower of London (TOL), a measure of central executive function) and five computerised (Bakan vigilance task, mental rotation, simple reaction time, immediate word recall and two-finger tapping) tasks. Women's body Fe ranged from - 4·2 to 8·1 mg/kg. General linear model ANOVA revealed a significant effect of body Fe on TOL planning time (P= 0.002). Spearman's correlation coefficients showed a significant inverse relationship between body Fe and TOL planning time for move categories 4 (r - 0.39, P= 0.01) and 5 (r - 0.47, P= 0.002). Performance on the computerised cognitive tasks was not affected by body Fe level. These findings suggest that Fe status in the absence of anaemia is positively associated with central executive function in otherwise healthy college women. Copyright © The Authors 2012.