Multistability in perception: binding sensory modalities, an overview

This special issue presents research concerning multistable perception in different sensory modalities. Multistability occurs when a single physical stimulus produces alternations between different subjective percepts. Multistability was first described for vision, where it occurs, for example, when different stimuli are presented to the two eyes or for certain ambiguous figures. It has since been described for other sensory modalities, including audition, touch and olfaction. The key features of multistability are: (i) stimuli have more than one plausible perceptual organization; (ii) these organizations are not compatible with each other. We argue here that most if not all cases of multistability are based on competition in selecting and binding stimulus information. Binding refers to the process whereby the different attributes of objects in the environment, as represented in the sensory array, are bound together within our perceptual systems, to provide a coherent interpretation of the world around us. We argue that multistability can be used as a method for studying binding processes within and across sensory modalities. We emphasize this theme while presenting an outline of the papers in this issue. We end with some thoughts about open directions and avenues for further research.     

Multistability,perceptual value,and internal foraging

1. Download : Download high-res image (105KB)
2. Download : Download full-size image

     

Quantitative analysis of EGR proteins binding to DNA: assessing additivity in both the binding site and the protein

Background  

Recognition codes for protein-DNA interactions typically assume that the interacting positions contribute additively to the binding energy. While this is known to not be precisely true, an additive model over the DNA positions can be a good approximation, at least for some proteins. Much less information is available about whether the protein positions contribute additively to the interaction.     

Regularities in the distribution of sweat glands and the principles of their grouping in man]

Under study were skin pieces from 80 regions of the body of 41 human fetuses and embryos, 5 corpses of newborns and 43 corpses of people of different age. Series of paraffin sections stained by conventional methods as well as total preparations and thick sections stained with methylene blue were examined. The laying of eccrine and apocrine sweat glands in the skin covered or not with hair was shown to occur repeatedly. Basing on the succession of their appearance they are called the glands of the first, second and third generations. The principle of grouping of eccrine sweat glands is shown both in the composition of glandular-hair complexes and in the groups independent of hair. The author proposes using of letter and figure symbols to signify variations of their disposition in formulars. The appocrine sweat glands are also laid repeatedly in the sites of their typical localization.     

NMR and X-ray analysis of structural additivity in metal binding site-swapped hybrids of rubredoxin

Background  

Chimeric hybrids derived from the rubredoxins of Pyrococcus furiosus (Pf) and Clostridium pasteurianum (Cp) provide a robust system for the characterization of protein conformational stability and dynamics in a differential mode. Interchange of the seven nonconserved residues of the metal binding site between the Pf and Cp rubredoxins yields a complementary pair of hybrids, for which the sum of the thermodynamic stabilities is equal to the sum for the parental proteins. Furthermore, the increase in amide hydrogen exchange rates for the hyperthermophile-derived metal binding site hybrid is faithfully mirrored by a corresponding decrease for the complementary hybrid that is derived from the less thermostable rubredoxin, indicating a degree of additivity in the conformational fluctuations that underlie these exchange reactions.     

Exploring additivity effects of double mutations on the binding affinity of protein‐protein complexes

Additivity in binding affinity of protein‐protein complexes refers to the change in free energy of binding (ΔΔG_bind) for double (or multiple) mutations which is approximately equal to the sum of their corresponding single mutation ΔΔG_bind values. In this study, we have explored the additivity effect of double mutants, which shows a linear relationship between the binding affinity of double and sum of single mutants with a correlation of 0.90. However, the comparison of ΔΔG_bind values showed a mean absolute deviation of 0.86 kcal/mol, and 25.6% of the double mutants show a deviation of more than 1 kcal/mol, which are identified as non‐additive. The additivity effects have been analyzed based on the influence of structural features such as accessible surface area, long range order, binding propensity change, surrounding hydrophobicity, flexibility, atomic contacts between the mutations and distance between the 2 mutations. We found that non‐additive mutations tend to be closer to each other and have more contacts. We have also used machine learning methods to discriminate additive and non‐additive mutations using structure‐based features, which showed the accuracies in the range of 0.77–0.92 for protein‐protein complexes belonging to different functions. Further, we have compared the additivity effects of protein stability along with binding affinity and explored the similarities and differences between them. The results obtained in this study provide insights into the effects of various structural features on binding affinity of double mutants, and will aid the development of accurate methods to predict the binding affinity of double mutants.     

Gene regulatory networks generating the phenomena of additivity, dominance and epistasis

We show how the phenomena of genetic dominance, overdominance, additivity, and epistasis are generic features of simple diploid gene regulatory networks. These regulatory network models are together sufficiently complex to catch most of the suggested molecular mechanisms responsible for generating dominant mutations. These include reduced gene dosage, expression or protein activity (haploinsufficiency), increased gene dosage, ectopic or temporarily altered mRNA expression, increased or constitutive protein activity, and dominant negative effects. As classical genetics regards the phenomenon of dominance to be generated by intralocus interactions, we have studied two one-locus models, one with a negative autoregulatory feedback loop, and one with a positive autoregulatory feedback loop. To include the phenomena of epistasis and downstream regulatory effects, a model of a three-locus signal transduction network is also analyzed. It is found that genetic dominance as well as overdominance may be an intra- as well as interlocus interaction phenomenon. In the latter case the dominance phenomenon is intimately connected to either feedback-mediated epistasis or downstream-mediated epistasis. It appears that in the intra- as well as the interlocus case there is considerable room for additive gene action, which may explain to some degree the predictive power of quantitative genetic theory, with its emphasis on this type of gene action. Furthermore, the results illuminate and reconcile the prevailing explanations of heterosis, and they support the old conjecture that the phenomenon of dominance may have an evolutionary explanation related to life history strategy.     

The thermodynamic principles of ligand binding in chromatography and biology

In chromatography, macromolecules do not adsorb in the traditional sense of the word but bind to ligands that are covalently bonded to the surface of the porous bead. Therefore, the adsorption must be modelled as a process where protein molecules bind to the immobilised ligands. The paper discusses the general thermodynamic principles of ligand binding. Models of the multi-component adsorption in ion-exchange and hydrophobic chromatography, HIC and RPLC, are developed. The parameters in the models have a well-defined physical significance. The models are compared to the Langmuir model. In the traditional adsorption models, the standard state Gibbs energy change of adsorption does not depend level of occupancy, but when it depends on the level of occupancy it gives rise to an adsorptive behaviour known as cooperativity. The binding of oxygen to haemoglobin is a well-known example from biology but it is also observed in chromatography due to protein-protein interactions. Retention measurements on beta-lactoglobulin A demonstrate this. A discussion of salt effects on hydrophobic interactions in precipitation and chromatography of proteins concludes the paper.     

Visual, haptic and cross-modal recognition of objects and scenes.

In this article we review current literature on cross-modal recognition and present new findings from our studies on object and scene recognition. Specifically, we address the questions of what is the nature of the representation underlying each sensory system that facilitates convergence across the senses and how perception is modified by the interaction of the senses. In the first set of our experiments, the recognition of unfamiliar objects within and across the visual and haptic modalities was investigated under conditions of changes in orientation (0 degrees or 180 degrees ). An orientation change increased recognition errors within each modality but this effect was reduced across modalities. Our results suggest that cross-modal object representations of objects are mediated by surface-dependent representations. In a second series of experiments, we investigated how spatial information is integrated across modalities and viewpoint using scenes of familiar, 3D objects as stimuli. We found that scene recognition performance was less efficient when there was either a change in modality, or in orientation, between learning and test. Furthermore, haptic learning was selectively disrupted by a verbal interpolation task. Our findings are discussed with reference to separate spatial encoding of visual and haptic scenes. We conclude by discussing a number of constraints under which cross-modal integration is optimal for object recognition. These constraints include the nature of the task, and the amount of spatial and temporal congruency of information across the modalities.     

Trichothecene synergism, additivity, and antagonism: the significance of the maximally quiescent ratio.

The interactive effect of the combinations of trichothecene mycotoxins often found in fungus infected plants, contaminated grain, and other biological systems is poorly understood. Growth inhibition of the yeast Kluyveromyces marxianus was used to measure the effects of HT-2 toxin, roridin A, and T-2 toxin as individual toxins or as binary mixtures. A value, the combination index, was derived which indicates the interactive effects of a binary mixture of toxins. The interaction is affected by the ratio of the individual toxins, and the percent inhibition of yeast growth. Generally the interaction of T-2 toxin and roridin A or T-2 toxin and HT-2 toxin changes from antagonistic when they cause a low percent inhibition of yeast growth to synergistic when they cause a high percent inhibition of yeast growth. Additionally, any two trichothecenes have a unique ratio, which we name the maximally quiescent ratio (or MQR), where there is the least change in the type and intensity of their interaction. The maximally quiescent ratio in this case has helped to define the nature of toxin interactions and could be used to provide insights into hormone, immune system, developmental, enzyme, and gene regulation, combined drug therapy, and the action of mixtures of natural or synthetic toxins, carcinogens, pesticides, and environmental pollutants.     

Multistability and metastability: understanding dynamic coordination in the brain

Multistable coordination dynamics exists at many levels, from multifunctional neural circuits in vertebrates and invertebrates to large-scale neural circuitry in humans. Moreover, multistability spans (at least) the domains of action and perception, and has been found to place constraints upon, even dictating the nature of, intentional change and the skill-learning process. This paper reviews some of the key evidence for multistability in the aforementioned areas, and illustrates how it has been measured, modelled and theoretically understood. It then suggests how multistability--when combined with essential aspects of coordination dynamics such as instability, transitions and (especially) metastability--provides a platform for understanding coupling and the creative dynamics of complex goal-directed systems, including the brain and the brain-behaviour relation.     

Nanomolar inhibition of the enterobactin biosynthesis enzyme, EntE: synthesis, substituent effects, and additivity

2,3-Dihydroxybenzohydroxamoyl adenylate (I) was prepared as a potential product analog inhibitor of EntE (EC# 2.7.7.58), a 2,3-dihydroxybenzoate AMP ligase from Escherichia coli that is required for the biosynthesis of enterobactin. This compound, obtained by the aqueous reaction of imidazole-activated adenosine 5'-phosphate and 2,3-dihydroxybenzohydroxamic acid, is a competitive inhibitor with a Ki value of 4.5 x 10(-9)M. Deletion of the catecholic 3-OH group of (I), in compound (II), reduced inhibitory activity by a factor of 3.5, whereas, removal of both the 3-OH and 2-OH groups, in (III), reduced inhibitory activity by a factor of approximately 2000. Acetohydroxamoyl adenylate (IV), in which the entire catechol moiety of (I) is replaced by a hydrogen atom, gave 相似文献   

Multistability and dynamic transitions of intracellular Min protein patterns

Cells owe their internal organization to self‐organized protein patterns, which originate and adapt to growth and external stimuli via a process that is as complex as it is little understood. Here, we study the emergence, stability, and state transitions of multistable Min protein oscillation patterns in live Escherichia coli bacteria during growth up to defined large dimensions. De novo formation of patterns from homogenous starting conditions is observed and studied both experimentally and in simulations. A new theoretical approach is developed for probing pattern stability under perturbations. Quantitative experiments and simulations show that, once established, Min oscillations tolerate a large degree of intracellular heterogeneity, allowing distinctly different patterns to persist in different cells with the same geometry. Min patterns maintain their axes for hours in experiments, despite imperfections, expansion, and changes in cell shape during continuous cell growth. Transitions between multistable Min patterns are found to be rare events induced by strong intracellular perturbations. The instances of multistability studied here are the combined outcome of boundary growth and strongly nonlinear kinetics, which are characteristic of the reaction–diffusion patterns that pervade biology at many scales.     

Toxicity of spinosad and Beauveria bassiana to the black cutworm,and the additivity of subletal doses

The main objective of this study was to assess the susceptibility of the black cutworm (Agrotis ipsilon) to the biopesticide spinosad and to a commercial formulation (GHA strain) of the entomopathogenic fungus, Beauveria bassiana. Secondly, we quantified the effects of sublethal doses of spinosad on a number of A. ipsilon fitness parameters, and interactions resulting from simultaneous applications of sub-lethal doses of spinosad and B. bassiana. Under laboratory conditions, A. ipsilon third instar larvae were highly susceptible to spinosad, with an estimated LC₅₀ of 50 ppm. The entomopathogenic fungus, B. bassiana had a lower efficacy with an estimated LC₅₀ of 7×107 spores mL^?1. Topical applications of 5, 7.5 and 10 ppm of spinosad on third instar larvae reduced larval size and increased time to pupation and to emergence. However, pupal and adult weights were not significantly different between treated and control individuals. Additivity was observed from most spinosad–B. bassiana combinations tested, thus indicating compatibility between products. We concluded that spinosad is a promising tool for controlling black cutworm larvae alone or in combination with other products.     

Interscaffolding additivity: binding of P1 variants of bovine pancreatic trypsin inhibitor to four serine proteases.

Different families of protein inhibitors of serine proteases share similar conformation of the enzyme-binding loop, while their scaffoldings are completely different. In the enzyme-inhibitor complex, the P1position of the loop makes numerous contacts within the S1pocket and significantly influences the energy of the interaction. Here, we determine the association energies (DeltaGavalues) for the interaction of coded P1variants of bovine pancreatic trypsin inhibitor (BPTI) with bovine beta-trypsin (BT), anionic salmon trypsin (AST), bovine alpha-chymotrypsin (BCHYM), and human neutrophil elastase (HNE). The respective DeltaGaranges are 15, 13, 9, and 8 kcal mol-1(1 cal=4.18 J). Next, through interscaffolding additivity cycles, we compare our set of DeltaGavalues determined for BCHYM and HNE with similar data sets available in the literature for three other inhibitor families. The analysis of the cycles shows that 27 to 83 % of cycles fulfil the criteria of additvity. In one particular case (comparison of associations of P1variants of BPTI and OMTKY3 with BCHYM) there is a structural basis for strongly non-additive behaviour. We argue that the interscaffolding additvity depends on sequential and conformational similarities of sites where the mutation(s) are introduced and on the particular substitution. In the second interscaffolding analysis, we compare binding of the same P1mutants to BT and AST. The high correlation coefficient shows that both trypsins recognize with comparable strength the non-cognate side-chains. However, the cognate Arg and Lys side-chains are recognized significantly more strongly by AST.