A common contrast pooling rule for suppression within and between the eyes

Recent work has revealed multiple pathways for cross-orientation suppression in cat and human vision. In particular, ipsiocular and interocular pathways appear to assert their influence before binocular summation in human but have different (1) spatial tuning, (2) temporal dependencies, and (3) adaptation after-effects. Here we use mask components that fall outside the excitatory passband of the detecting mechanism to investigate the rules for pooling multiple mask components within these pathways. We measured psychophysical contrast masking functions for vertical 1 cycle/deg sine-wave gratings in the presence of left or right oblique (645 deg) 3 cycles/deg mask gratings with contrast C%, or a plaid made from their sum, where each component (i) had contrast 0.5Ci%. Masks and targets were presented to two eyes (binocular), one eye (monoptic), or different eyes (dichoptic). Binocular-masking functions superimposed when plotted against C, but in the monoptic and dichoptic conditions, the grating produced slightly more suppression than the plaid when Ci $ 16%. We tested contrast gain control models involving two types of contrast combination on the denominator: (1) spatial pooling of the mask after a local nonlinearity (to calculate either root mean square contrast or energy) and (2) "linear suppression" (Holmes & Meese, 2004, Journal of Vision 4, 1080–1089), involving the linear sum of the mask component contrasts. Monoptic and dichoptic masking were typically better fit by the spatial pooling models, but binocular masking was not: it demanded strict linear summation of the Michelson contrast across mask orientation. Another scheme, in which suppressive pooling followed compressive contrast responses to the mask components (e.g., oriented cortical cells), was ruled out by all of our data. We conclude that the different processes that underlie monoptic and dichoptic masking use the same type of contrast pooling within their respective suppressive fields, but the effects do not sum to predict the binocular case.

Contextual modulation involves suppression and facilitation from the center and the surround

In psychophysics, cross-orientation suppression (XOS) and cross-orientation facilitation (XOF) have been measured by investigating mask configuration on the detection threshold of a centrally placed patch of sine-wave grating. Much of the evidence for XOS and XOF comes from studies using low and high spatial frequencies, respectively, where the interactions are thought to arise from within (XOS) and outside (XOF) the footprint of the classical receptive field. We address the relation between these processes here by measuring the effects of various sizes of superimposed and annular cross-oriented masks on detection thresholds at two spatial scales (1 and 7 c/deg) and on contrast increment thresholds at 7 c/deg. A functional model of our results indicates the following (1) XOS and XOF both occur for superimposed and annular masks. (2) XOS declines with spatial frequency but XOF does not. (3) The spatial extent of the interactions does not scale with spatial frequency, meaning that surround-effects are seen primarily at high spatial frequencies. (4) There are two distinct processes involved in XOS: direct divisive suppression and modulation of self-suppression. (5) Whether XOS or XOF wins out depends upon their relative weights and mask contrast. These results prompt enquiry into the effect of spatial frequency at the single-cell level and place new constraints on image-processing models of early visual processing. © ARVO.

Spatial and temporal dependencies of cross-orientation suppression in human vision.

A well-known property of orientation-tuned neurons in the visual cortex is that they are suppressed by the superposition of an orthogonal mask. This phenomenon has been explained in terms of physiological constraints (synaptic depression), engineering solutions for components with poor dynamic range (contrast normalization) and fundamental coding strategies for natural images (redundancy reduction). A common but often tacit assumption is that the suppressive process is equally potent at different spatial and temporal scales of analysis. To determine whether it is so, we measured psychophysical cross-orientation masking (XOM) functions for flickering horizontal Gabor stimuli over wide ranges of spatio-temporal frequency and contrast. We found that orthogonal masks raised contrast detection thresholds substantially at low spatial frequencies and high temporal frequencies (high speeds), and that small and unexpected levels of facilitation were evident elsewhere. The data were well fit by a functional model of contrast gain control, where (i) the weight of suppression increased with the ratio of temporal to spatial frequency and (ii) the weight of facilitatory modulation was the same for all conditions, but outcompeted by suppression at higher contrasts. These results (i) provide new constraints for models of primary visual cortex, (ii) associate XOM and facilitation with the transient magno- and sustained parvostreams, respectively, and (iii) reconcile earlier conflicting psychophysical reports on XOM.

Interocular suppression is gated by interocular feature matching

We present a new form of contrast masking in which the target is a patch of low spatial frequency grating (0.46 c/deg) and the mask is a dark thin ring that surrounds the centre of the target patch. In matching and detection experiments we found little or no effect for binocular presentation of mask and test stimuli. But when mask and test were presented briefly (33 or 200 ms) to different eyes (dichoptic presentation), masking was substantial. In a 'half-binocular' condition the test stimulus was presented to one eye, but the mask stimulus was presented to both eyes with zero-disparity. This produced masking effects intermediate to those found in dichoptic and full-binocular conditions. We suggest that interocular feature matching can attenuate the potency of interocular suppression, but unlike in previous work (McKee, S. P., Bravo, M. J., Taylor, D. G., & Legge, G. E. (1994) Stereo matching precedes dichoptic masking. Vision Research, 34, 1047) we do not invoke a special role for depth perception. © 2004 Elsevier Ltd. All rights reserved.

Characterization of tissue transglutaminase 2 in macrophage function

Programmed cell death, apoptosis, is a highly regulated process that removes damaged or unwanted cells in vivo and has significant immunological implications. Defective clearance of apoptotic cells by macrophages (professional phagocytes) is known to result in chronic inflammatory and autoimmune disease. Tissue transglutaminase 2 (TG2) is a Ca2+-dependent protein cross linking enzyme known to play an important role in a number of cell functions. Up-regulation of TG2 is thought to be involved in monocyte to macrophage differentiation and defective clearance of apoptotic cells by TG2 null mice has been described though in this context the role of TG2 is yet to be fully elucidated. Cell surface-associated TG2 is now recognized as being important in regulating cell adhesion and migration, via its association with cell surface receptors such as syndecan-4, ß1 and ß3 integrin, but its extracellular role in the clearance of apoptotic cells is still not fully explored. Our work aims to characterize the role of TG2 and its partners (e.g. syndecan-4 and ß3 integrin) in macrophage function within the framework of apoptotic cell clearance. Both THP-1 cell-derived macrophage-like cells and primary human macrophages were analyzed for the expression and function of TG2. Macrophage-apoptotic cell interaction studies in the presence of TG2 inhibitors (both cell permeable and impermeable, irreversible and active site directed) resulted in significant inhibition of interaction indicating a possible role for TG2 in apoptotic cell clearance. Macrophage cell surface TG2 and, in particular, its cell surface crosslinking activity was found to be crucial in dictating apoptotic cell clearance. Our further studies demonstrate syndecan-4 association with TG2 and imply possible cooperation of these proteins in apoptotic cell clearance. Knockdown studies of syndecan-4 reveal its importance in apoptotic cell clearance. Our current findings suggest that TG2 has a crucial but yet to be fully defined role in apoptotic cell clearance which seems to involve protein cross linking and interaction with other cell surface receptors.

Analysis of Transglutaminase-2 in macrophage function

Programmed cell death, apoptosis, is a highly regulated process that removes damaged or unwanted cells in vivo and has significant immunological implications. Defective clearance of apoptotic cells by macrophages (professional phagocytes) is known to result in chronic inflammatory and autoimmune disease. Transglutaminase-2 (TG2) is a Ca2+-dependent protein crosslinking enzyme known to play an important role in apoptotic cell clearance by macrophages through an ill-defined mechanism. Several studies have implicated TG2 in the apoptosis programme e.g. raised TG2 levels in cells undergoing apoptosis; increased cell death with down-regulation of TG2; up-regulation of TG2 in monocytes upon differentiation into macrophages. Defective clearance of apoptotic cells by TG2 null mice has been described though in this context the role of TG2 is yet to be elucidated. Here we aim to characterise the role of TG2 in macrophage function with a focus on apoptotic cell clearance. THP-1 monocytes were induced to differentiate to macrophage-like cells by three different stimulants and were analysed for the presence of TG2. Macrophage-apoptotic cell interaction studies in the presence and absence of irreversible TG2 inhibitors resulted in significant inhibition of interaction indicating a possible role for TG2 in apoptotic cell clearance. TG2 was expressed at the macrophage cell surface and its association with ß3 integrin expression suggests the possible link between TG2 and ß3 integrins. Our current findings suggest that TG2 had got a crucial but yet to be defined role in apoptotic cell clearance.

Pulse tail suppression in laser diode output by tunable notch filter

Efficient suppression of relaxation oscillations in the output signal from an overdriven gain-switched laser diode was demonstrated. Several quantum-well distributed feedback laser diodes from different manufacturers were used for experimental analysis. A five-fold increase in the peak power was achieved for the tail-free operation. It was found that spectral filtering removed the nonlinearly chirped components resulting in pulse shortening by a factor of three.

Apoptotic cell-derived ICAM-3 promotes both macrophage chemoattraction to and tethering of apoptotic cells

Damaged, aged or unwanted cells are removed from the body by an active process known as apoptosis. This highly orchestrated programme results in cell disassembly and the exposure of ‘flags’ at the dying cell surface that permit recognition and removal by viable cells (phagocytes). Efficient phagocytic removal of dying cells is essential to prevent inflammatory and autoimmune disorders. Relatively little is known of the molecular mechanisms underlying changes at the apoptotic cell surface. We have previously shown that ICAM-3 (a heavily glycosylated, leukocyte-restricted Immunoglobulin Super-Family member) undergoes a change of function as cells die so that it acts as a molecular ‘flag’ to mediate corpse removal. Our work seeks to characterise apoptosis-associated changes in ICAM-3 and define their role in ICAM-3’s novel function in apoptotic cell clearance. Here we extend earlier studies to show that apoptotic cell-associated ICAM-3 functions, at least minimally, to tether apoptotic leukocytes to macrophages via an undefined receptor. Whilst CD14 has been suggested as a possible innate immune receptor for apoptotic cell-associated ICAM-3, we demonstrate ICAM-3 functions for apoptotic cell clearance in the absence of CD14. Our data additionally indicate, that during apoptosis, leukocytes display early changes in cell surface glycosylation and a marked reduction in ICAM-3, a change that correlates with a reduction in cell volume. This reduction in ICAM-3 is explained by cell surface shedding of microparticles (‘apoptotic bodies’) that contain ICAM-3. Such microparticles, released from apoptotic leukocytes, are strongly chemoattractive for macrophages. In addition, microparticles from ICAM-3-deficient leukocytes are significantly less chemoattractive than microparticles from their ICAM-3-replete counterparts. Taken together these data support the hypothesis that ICAM-3 acts as an apoptotic cell-associated ligand to tether dying cells to phagocytes in a CD14-independent manner. Furthermore our data suggest that released ICAM-3 may promote the recruitment of phagocytes to sites of leukocyte apoptosis.

Apoptotic cell-derived ICAM-3 promotes both macrophage chemoattraction to and tethering of apoptotic cells

A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging molecules have been implicated within the complex sequential processes that result in phagocytosis and degradation of apoptotic cells. Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance, although its precise role in the clearance process is ill defined. The main objective of this work is to further characterise the function of ICAM-3 in the removal of apoptotic cells. Using a range of novel anti-ICAM-3 monoclonal antibodies (mAbs), including one (MA4) that blocks apoptotic cell clearance by macrophages, alongside apoptotic human leukocytes that are normal or deficient for ICAM-3, we demonstrate that ICAM-3 promotes a domain 1-2-dependent tethering interaction with phagocytes. Furthermore, we demonstrate an apoptosis-associated reduction in ICAM-3 that results from release of ICAM-3 within microparticles that potently attract macrophages to apoptotic cells. Taken together, these data suggest that apoptotic cell-derived microparticles bearing ICAM-3 promote macrophage chemoattraction to sites of leukocyte cell death and that ICAM-3 mediates subsequent cell corpse tethering to macrophages. The defined function of ICAM-3 in these processes and profound defect in chemotaxis noted to ICAM-3-deficient microparticles suggest that ICAM-3 may be an important adhesion molecule involved in chemotaxis to apoptotic human leukocytes. © 2012 Macmillan Publishers Limited All rights reserved.

Pooling and suppression in human spatial vision

A distinct feature of several recent models of contrast masking is that detecting mechanisms are divisively inhibited by a broadly tuned ‘gain pool’ of narrow-band spatial pattern mechanisms. The contrast gain control provided by this ‘cross-channel’ architecture achieves contrast normalisation of early pattern mechanisms, which is important for keeping them within the non-saturating part of their biological operating characteristic. These models superseded earlier ‘within-channel’ models, which had supposed that masking arose from direct stimulation of the detecting mechanism by the mask. To reveal the extent of masking, I measured the levels produced with large ranges of pattern spatial relationships that have not been explored before. Substantial interactions between channels tuned to different orientations and spatial frequencies were found. Differences in the masking levels produced with single and multiple component mask patterns provided insights into the summation rules within the gain pool. A widely used cross-channel masking model was tested on these data and was found to perform poorly. The model was developed and a version in which linear summation was allowed between all components within the gain pool but with the exception of the self-suppressing route typically provided the best account of the data. Subsequently, an adaptation paradigm was used to probe the processes underlying pooled responses in masking. This delivered less insight into the pooling than the other studies and areas were identified that require investigation for a new unifying model of masking and adaptation. In further experiments, levels of cross-channel masking were found to be greatly influenced by the spatio-temporal tuning of the channels involved. Old masking experiments and ideas relying on within-channel models were re-elevated in terms of contemporary cross-channel models (e.g. estimations of channel bandwidths from orientation masking functions) and this led to different conclusions than those originally arrived at. The investigation of effects with spatio-temporally superimposed patterns is focussed upon throughout this work, though it is shown how these enquiries might be extended to investigate effects across spatial and temporal position.

Subspace modelling for structured noise suppression

The problem of structured noise suppression is addressed by i)modelling the subspaces hosting the components of the signal conveying the information and ii)applying a nonlin- ear non-extensive technique for effecting the right separation. Although the approach is applicable to all situations satisfying the hypothesis of the proposed framework, this work is motivated by a particular scenario, namely, the cancellation of low frequency noise in broadband seismic signals.

Orientation masking and cross-orientation suppression (XOS):implications for estimates of channel bandwidth

Most contemporary models of spatial vision include a cross-oriented route to suppression (masking from a broadly tuned inhibitory pool), which is most potent at low spatial and high temporal frequencies (T. S. Meese & D. J. Holmes, 2007). The influence of this pathway can elevate orientation-masking functions without exciting the target mechanism, and because early psychophysical estimates of filter bandwidth did not accommodate this, it is likely that they have been overestimated for this corner of stimulus space. Here we show that a transient 40% contrast mask causes substantial binocular threshold elevation for a transient vertical target, and this declines from a mask orientation of 0° to about 40° (indicating tuning), and then more gently to 90°, where it remains at a factor of ∼4. We also confirm that cross-orientation masking is diminished or abolished at high spatial frequencies and for sustained temporal modulation. We fitted a simple model of pedestal masking and cross-orientation suppression (XOS) to our data and those of G. C. Phillips and H. R. Wilson (1984) and found the dependency of orientation bandwidth on spatial frequency to be much less than previously supposed. An extension of our linear spatial pooling model of contrast gain control and dilution masking (T. S. Meese & R. J. Summers, 2007) is also shown to be consistent with our results using filter bandwidths of ±20°. Both models include tightly and broadly tuned components of divisive suppression. More generally, because XOS and/or dilution masking can affect the shape of orientation-masking curves, we caution that variations in bandwidth estimates might reflect variations in processes that have nothing to do with filter bandwidth.

Characterization of tissue transglutaminase 2 in macrophage function

Apoptosis is a highly regulated process that removes damaged or unwanted cells in vivo and defective clearance of apoptotic cells by macrophages has significant immunological implications. Tissue transglutaminase 2 (TG2) is a Ca2+-dependent protein cross linking enzyme known to play an important role in cell proliferation, differentiation, carcinogenesis, programmed death, and aging. TG2 as a guanosine triphosphate (GTP)-binding or GTP- hydrolyzing protein for mediating signal transduction and as a cell cycle regulator emphasized the importance of this enzyme in aging process. The ubiquitous presence of TG2 compared to the other organ-specific TGases has attracted special attention as a cellular aging device. TG2 activity and expression are known to increase in aging humans suggesting possible involvement in several age-related processes such as decrease in vascular compliance and increased stiffening of conduit arteries, cataract formation, Alzheimer's disease and senescent epidermal keratinocytes. Our work aims to characterize the role of TG2 and its partners (e.g. syndecan-4 and ß3 integrin) in macrophage function. THP-1 cell derived macrophage-like cells and primary human macrophages were analyzed for the expression and function of TG2. Macrophage-apoptotic cell interaction studies in the presence of TG2 inhibitors resulted in significant inhibition of interaction. Macrophage cell surface TG2 and, in particular, its cell surface cross linking activity was found to be crucial in apoptotic cell clearance. Syndecan-4 association with TG2 implies possible cooperation of these proteins and knockdown studies of syndecan-4 reveal its importance in apoptotic cell clearance. Our current findings suggest that TG2 has a crucial but yet to be fully defined role in apoptotic cell clearance.

Interocular suppression in normal and amblyopic vision:spatio-temporal properties

We measured the properties of interocular suppression in strabismic amblyopes and compared these to dichoptic masking in binocularly normal observers. We used a dichoptic version of the well-established probed-sinewave paradigm that measured sensitivity to a brief target stimulus (one of four letters to be discriminated) in the amblyopic eye at different times relative to a suppression-inducing mask in the fixing eye. This was done using both sinusoidal steady state and transient approaches. The suppression-inducing masks were either modulations of luminance or contrast (full field, just overlaying the target, or just surrounding the target). Our results were interpreted using a descriptive model that included contrast gain control and spatio-temporal filtering prior to excitatory binocular combination. The suppression we measured, other than in magnitude, was not fundamentally different from normal dichoptic masking: lowpass spatio-temporal properties with similar contributions from both surround and overlay suppression.