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Neural mechanisms for the recognition of biological movements.

The visual recognition of complex movements and actions is crucial for the survival of many species. It is important not only for communication and recognition at a distance, but also for the learning of complex motor actions by imitation. Movement recognition has been studied in psychophysical, neurophysiological and imaging experiments, and several cortical areas involved in it have been identified. We use a neurophysiologically plausible and quantitative model as a tool for organizing and making sense of the experimental data, despite their growing size and complexity. We review the main experimental findings and discuss possible neural mechanisms, and show that a learning-based, feedforward model provides a neurophysiologically plausible and consistent summary of many key experimental results.

Animals↗

Systematic mining and quantification reveal the dominant contribution of non-HLA variations to acute graft-versus-host disease.

Human leukocyte antigen (HLA) disparity between donors and recipients is a key determinant triggering intense alloreactivity, leading to a lethal complication, namely, acute graft-versus-host disease (aGVHD), after allogeneic transplantation. Moreover, aGVHD remains a cause of mortality after HLA-matched allogeneic transplantation. Protocols for HLA-haploidentical hematopoietic cell transplantation (haploHCT) have been established successfully and widely applied, further highlighting the urgency of performing panoramic screening of non-HLA variations correlated with aGVHD. On the basis of our time-consecutive large haploHCT cohort (with a homogenous discovery set and an extended confirmatory set), we first delineated the genetic landscape of 1366 samples to quantitatively model aGVHD risk by assessing the contributions of HLA and non-HLA genes together with clinical factors. In addition to identifying multiple loss-of-function (LoF) risk variations in non-HLA coding genes, our data-driven study revealed that non-HLA genetic variations, independent of HLA disparity, contributed the most to the occurrence of aGVHD. This unexpected major effect was verified in an independent cohort that received HLA-identical sibling HCT. Subsequent functional experiments further revealed the roles of a representative non-HLA LoF gene and LoF gene pair in regulating the alloreactivity of primary human T cells. Our findings highlight the importance of non-HLA genetic risk in the new era of transplantation and propose a new direction to explore the immunogenetic mechanism of alloreactivity and to optimize donor selection strategies for allogeneic transplantation.

Humans↗

Use of protamine to augment adenovirus-mediated cancer gene therapy.

Improving the therapeutic potential of adenoviral (Ad) suicide gene therapy has become an area of intense investigation since the inception of gene therapy strategies for cancer treatment. Poor efficiency of gene transfer to target tissues has become one of the most important limitations to Ad-based gene therapy. Since polycations have been shown to enhance adenovirus-mediated gene transfer in epithelial cells both in vitro and in vivo, we hypothesized that polycations could augment treatment efficacy in animals with established tumor. To address this hypothesis, protamine sulfate, a polycation already safely administered in humans, was complexed with a recombinant Ad (E1E3-deleted) vector containing the herpes simplex 1 thymidine kinase (HSVtk) suicide gene to treat cancer cell lines in vitro and in animals bearing intraperitoneal tumor. In the presence of 5 microg/ml protamine, the efficiency of gene transfer to a number of cancer cell lines normally resistant to adenovirus was significantly enhanced. Protamine's effect in vitro was found to be inversely proportional to the level of expression of the high affinity Ad binding site, coxsackievirus and adenovirus receptor (CAR), on the sur- face of the various cell lines tested. Ad.tk infected tumor cells were rendered 2.5- to three-fold more sensitive to 20 microM ganciclovir (GCV) in the presence of protamine. Protamine also augmented the in vivo transfer efficiency of the marker gene, LacZ (contained in an Ad vector), on the surface of tumors derived from an intraperitoneal mouse model. Quantitative imaging revealed 50% tumor surface transduced with LacZ when treatment was performed in the presence of 50 microg/ml protamine compared with 12% tumor surface in controls. However, experiments performed utilizing intraperitoneal administration of Ad.tk/GCV in the presence or absence of 50 microg/ml protamine demonstrated no significantly improved median survival in mice bearing established intraperitoneal tumors. Similarly, in Fischer rats bearing intrapleural tumor, no improvement in anti-tumor response was observed when Ad treatment was performed intrapleurally in the presence of protamine. Thus, although protamine induced an enhancement of Ad-mediated gene transfer in vitro and in vivo, its use as an adjunct to intracavitary Ad-based cancer gene therapy in vivo appears to be limited.

Adenoviridae↗

Molecular analysis integrating different pathways associated with androgen-independent progression in LuCaP 23.1 xenograft.

After therapeutic hormone deprivation, most prostate cancer (PrCa) cells develop androgen-independent (AI) growth. PrCa is highly heterogeneous and multifocal, suggesting that several molecular processes or pathways may be contributing to AI. The human LuCaP 23.1 xenograft model retains clinical hallmarks of PrCa, including heterogeneous growth, PSA production, androgen-responsiveness and progression to AI. In this work, we studied the effect of androgen depletion (castration) on the growth of LuCaP 23.1 xenografts. A total of 100 nude mice were implanted and analysed for their growth profiles before and after castration. By 11 and 15 weeks, tumours were harvested and assessed for molecular marker expression specific for PrCa. Prior to castration we found 37 fast growing (FG) tumours (948.9+/-76.9 mm(3)) and 63 slow growing (SG) tumours (229.6+/-18.4 mm(3)), a previously undescribed result for this PrCa model. Quantitative RT-PCR showed that in comparison to SGs, FGs contained high HER1, uPA and thymidilate synthetase (TS) expression with low levels of 5alpha-reductase 2 mRNA. All FG tumours progressed rapidly to AI growth 5 weeks after castration (FG-P). In SG castrated tumours, 66% of tumours (SG-P) showed retarded progression (by 12 weeks) to AI, whereas 34% responded to castration (SG-R). Molecular analysis permitted us to define distinct molecular profiles integrating different pathways associated with AI progression. FG-P, and a subgroup of SG-P tumours, presented significantly high levels of peptidylglycine alpha-amidating monooxygenase (PAM), HER1, HER2, TS, and uPA mRNA, all of which correlated with AR expression. The second subgroup of SG-P tumours showed overexpression of the antiapoptotic gene Bcl-2. A third subgroup of SG-P tumours showed significant expression of hypoxia-related gene (adrenomedullin) after castration. This work permitted to define distinct molecular profiles related to different AI growth in the LuCaP 23.1 xenograft.

Androgens↗

Regulation of yeast acetohydroxyacid synthase by valine and ATP.

The first step in the common pathway for the biosynthesis of branched-chain amino acids is catalysed by acetohydroxyacid synthase (AHAS; EC 4.1.3.18). The enzyme is found in plants, fungi and bacteria, and is regulated by controls on transcription and translation, and by allosteric modulation of catalytic activity. It has long been known that the bacterial enzyme is composed of two types of subunit, and a similar arrangement has been found recently for the yeast and plant enzymes. One type of subunit contains the catalytic machinery, whereas the other has a regulatory function. Previously, we have shown [Pang and Duggleby (1999) Biochemistry 38, 5222--5231] that yeast AHAS can be reconstituted from its separately purified subunits. The reconstituted enzyme is inhibited by valine, and ATP reverses this inhibition. In the present work, we further characterize the structure and the regulatory properties of reconstituted yeast AHAS. High phosphate concentrations are required for reconstitution and it is shown that these conditions are necessary for physical association between the catalytic and regulatory subunits. It is demonstrated by CD spectral changes that ATP binds to the regulatory subunit alone, most probably as MgATP. Neither valine nor MgATP causes dissociation of the regulatory subunit from the catalytic subunit. The specificity of valine inhibition and MgATP activation are examined and it is found that the only effective analogue of either regulator of those tested is the non-hydrolysable ATP mimic, adenosine 5'-[beta,gamma-imido]triphosphate. The kinetics of regulation are studied in detail and it is shown that the activation by MgATP depends on the valine concentration in a complex manner that is consistent with a proposed quantitative model.

Acetolactate Synthase↗

Activities and some properties of adenylate cyclase and phosphodiesterase in muscle, liver and nervous tissues from vertebrates and invertebrates in relation to the control of the concentration of adenosine 3':5'-cyclic monophosphate.

1. The basal and fluoride-stimulated activities of adenylate cyclase, and the maximal activities of 3':5'-cyclic AMP phosphodiesterase and 3':5'-cyclic GMP phosphodiesterase, together with the Km values for their respective substrates, were measured in muscle, liver and nervous tissues from a large range of animals to provide information on the mechanism of control of cyclic AMP concentrations in these tissues. High activities of adenylate cyclase and cyclic AMP diesterase are found in nervous tissues and in the more aerobic muscles (e.g. insect flight muscles, cardiac muscle and some vertebrate skeletal muscles). The activities of these enzymes in liver are similar to those in the heart of the same animal. The Km values for the enzymes from different tissues and animals are remarkably similar. 2. The comparison of cyclic AMP phosphodiesterase and cyclic GMP phosphodiesterase activities suggests that in vertebrate tissues only one enzyme (the high-Km enzyme), which possesses dual specificity, exists, whereas in invertebrate tissues there are at least two phosphodiesterases with separate specificities. 3. A simple quantitative model to explain the control of the steady-state concentrations of cyclic AMP is proposed. The maximum increase in cyclic AMP concentration predicted by comparison of basal with fluoride-stimulated activities of adenylate cyclase is compared with the maximum increases in concentration produced in the intact tissue by hormonal stimulation: reasonable agreement is obtained. The model is also used to predict the actual concentrations and the rates of turnover of cyclic AMP in different tissues and, where possible, these values are compared with reported values. Reasonable agreement is found between predicted and reported values. The possible physiological significances of different rates of turnover of cyclic AMP and the different ratios of high- and low-Km phosphodiesterases in different tissues are discussed.

Adenylyl Cyclases↗

C-signal: a cell surface-associated morphogen that induces and co-ordinates multicellular fruiting body morphogenesis and sporulation in Myxococcus xanthus.

In Myxococcus xanthus, morphogenesis of multicellular fruiting bodies and sporulation are co-ordinated temporally and spatially. csgA mutants fail to synthesize the cell surface-associated C-signal and are unable to aggregate and sporulate. We report that csgA encodes two proteins, a 25 kDa species corresponding to full-length CsgA protein and a 17 kDa species similar in size to C-factor protein, which has been shown previously to have C-signal activity. By systematically varying the accumulation of the csgA proteins, we show that overproduction of the csgA proteins results in premature aggregation and sporulation, uncoupling of the two events and the formation of small fruiting bodies, whereas reduced synthesis of the csgA proteins causes delayed aggregation, reduced sporulation and the formation of large fruiting bodies. These results show that C-signal induces aggregation as well as sporulation, and that an ordered increase in the level of C-signalling during development is essential for the spatial co-ordination of these events. The results support a quantitative model, in which aggregation and sporulation are induced at distinct threshold levels of C-signalling. In this model, the two events are temporally co-ordinated by the regulated increase in C-signalling levels during development. The contact-dependent C-signal transmission mechanism allows the spatial co-ordination of aggregation and sporulation by coupling cell position and signalling levels.

Bacterial Proteins↗

Intracellular translation initiation factor levels in Saccharomyces cerevisiae and their role in cap-complex function.

Knowledge of the balance of activities of eukaryotic initiation factors (eIFs) is critical to our understanding of the mechanisms underlying translational control. We have therefore estimated the intracellular levels of 11 eIFs in logarithmically growing cells of Saccharomyces cerevisiae using polyclonal antibodies raised in rabbits against recombinant proteins. Those factors involved in 43S complex formation occur at levels comparable (i.e. within a 0.5- to 2.0-fold range) to those published for ribosomes. In contrast, the subunits of the cap-binding complex eIF4F showed considerable variation in their abundance. The helicase eIF4A was the most abundant eIF of the yeast cell, followed by eIF4E at multiple copies per ribosome, and eIF4B at approximately one copy per ribosome. The adaptor protein eIF4G was the least abundant of the eIF4 factors, with a copy number per cell that is substoichiometric to the ribosome and similar to the abundance of mRNA. The observed excess of eIF4E over its functional partner eIF4G is not strictly required during exponential growth: at eIF4E levels artificially reduced to 30% of those in wild-type yeast, growth rates and the capacity for general protein synthesis are only minimally affected. This demonstrates that eIF4E does not exercise a higher level of rate control over translation than other eIFs. However, other features of the yeast life cycle, such as the control of cell size, are more sensitive to changes in eIF4E abundance. Overall, these data constitute an important basis for developing a quantitative model of the workings of the eukaryotic translation apparatus.

Animals↗

Chloride-dependent transport of NH4+ into bee retinal glial cells.

Mammalian astrocytes convert glutamate to glutamine and bee retinal glial cells convert pyruvate to alanine. To maintain such amination reactions these glial cells may take up NH4+/NH3. We have studied the entry of NH4+/NH3 into bundles of glial cells isolated from bee retina by using the fluorescent dye BCECF to measure pH. Ammonium caused intracellular pH to decrease by a saturable process: the rate of change of pH was maximal for an ammonium concentration of about 5 mM. This acidifying response to ammonium was abolished by the loop diuretic bumetanide (100 microM) and by removal of extracellular Cl-. These results strongly suggest that ammonium enters the cell by contransport of NH4+ with Cl-. Removal of extracellular Na+ did not abolish the NH(4+)-induced acidification. The NH(4+)-induced pH change was unaffected when nearly all K+ conductance was blocked with 5 mM Ba2+ showing that NH4+ did not enter through Ba(2+)-sensitive ion channels. Application of 2 mM NH4+ led to a large increase in total intracellular proton concentration estimated to exceed 13.5 mEq/L. As the cell membrane appeared to be permeable to NH3, we suggest that when NH4+ entered the cells, NH3 left, so that protons were shuttled into the cell. This shuttle, which was strongly dependent on internal and external pH, was quantitatively modelled. In retinal slices, 2 mM NH4+ alkalinized the extracellular space: this alkalinization was reduced in the absence of bath Cl-. We conclude that NH4+ enters the glial cells in bee retina on a cotransporter with functional similarities to the NH4+(K+)-Cl- cotransporter described in kidney cells.

Animals↗

Evolution of the human hand: approaches to acquiring, analysing and interpreting the anatomical evidence.

The discovery of fossil hand bones from an early human ancestor at Olduvai Gorge in 1960, at the same level as primitive stone tools, generated a debate about the role of tools in the evolution of the human hand that has raged to the present day. Could the Olduvai hand have made the tools? Did the human hand evolve as an adaptation to tool making and tool use? The debate has been fueled by anatomical studies comparing living and fossil human and nonhuman primate hands, and by experimental observations. These have assessed the relative abilities of apes and humans to manufacture the Oldowan tools, but consensus has been hampered by disagreements about how to translate experimental data from living species into quantitative models for predicting the performance of fossil hands. Such models are now beginning to take shape as new techniques are applied to the capture, management and analysis of data on kinetic and kinematic variables ranging from hand joint structure, muscle mechanics, and the distribution and density of bone to joint movements and muscle recruitment during manipulative behaviour. The systematic comparative studies are highlighting a functional complex of features in the human hand facilitating a distinctive repertoire of grips that are apparently more effective for stone tool making than grips characterising various nonhuman primate species. The new techniques are identifying skeletal variables whose form may provide clues to the potential of fossil hominid hands for one-handed firm precision grips and fine precision manoeuvering movements, both of which are essential for habitual and effective tool making and tool use.

Animals↗

A mechanistic study of evolvability using the mitogen-activated protein kinase cascade.

Evolvability is a function of the way genetic variation interacts with the mechanisms that produce the phenotype. We explore an explicitly mechanistic way of studying the evolvability of phenotypes that are produced by a relatively simple genetic mechanism, the mitogen-activated protein kinase (MAPK) cascade. We developed a quantitative model of MAPK activation that can be used to study the effects of genetic variation on the various components of this signaling cascade. We show how some standard tools of applied mathematics, such as steady-state formulations and nondimensionalization, can be used to elucidate the relative importance of variation in each gene of this mechanism. We also give insights into non-intuitive patterns of dependence and trade-off among the genes. The mechanism produces several different phenotypes (ultrasensitivity to stimulation, switch-like behavior, amount of MAPK-PP delivered, persistence of MAPK-PP activity), each of which is sensitive to different (but partially overlapping) combinations of genes. We show that the mechanism imposes clear limitations on the evolvability of each of the different phenotypes of the pathway, even in the presence of genetic variation in the components of the mechanism. This approach to the study of evolvability is generally applicable and complements the traditional approach through statistical genetics by providing a mechanistic understanding of the genetic interactions that produce the phenotype.

Biological Evolution↗

Indole-based analogs of melatonin: in vitro antioxidant and cytoprotective activities.

The known neuroprotective actions of melatonin could be due to its antioxidant or radical scavenging activity, or they could be due to specific interactions of the indole with its receptors. A study of structure-activity relationships may provide useful information when a validated macromolecular target has not been (or is not) identified. A set of indole derivatives, with changes in the 5-methoxy and acylamino groups, the side chain position and the lipophilic/hydrophilic balance, were selected and tested for their in vitro antioxidant potency in the ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid disodium salt) and thiobarbituric acid reactive substances (TBARS) assays and for their cytoprotective activity against kainate excitotoxicity on cerebellar cell cultures. No quantitative model was able to relate the potencies obtained in the two antioxidant assays, probably because they are related to different physico-chemical properties. However, the lipophilicity of the compounds and the antioxidant potency in the TBARS assay were linearly correlated. This may be due to improved access to the lipidic substrate, where the antioxidant action occurs. In the cytoprotection assay, most compounds showed potencies comparable with or lower than melatonin. An exception was N-[2-(5-methoxy-1H-indol-2-yl)ethyl]acetamide (12), yielding, at 50 microM, percentages of cell vitality higher than 75%, while melatonin EC50 was 333 microM. No correlation was observed between cytoprotective and antioxidant potencies, nor with MT1 or MT(2) receptor affinity. Compound 12 is a low-affinity antagonist at melatonin membrane receptors, and one of the most potent compounds in the antioxidant assays; its cytoprotective potency and the absence of agonist activity at melatonin membrane receptors make it a valid candidate for further investigations.

Animals↗

Assessment of the effects of breast cancer on bone and the response to therapy.

The skeleton is the most frequent site of metastatic disease in breast cancer and also the site of greatest morbidity. In addition, there is now recognition that accelerated bone loss associated with chemotherapy or hormonal therapy leads to an increased risk of osteoporosis in long-term breast cancer survivors. An improved range of treatment options is available and assessment of skeletal response both to the disease and to therapy is therefore of growing importance. Plain radiographs remain widely used to assess response, but are of limited sensitivity. The isotope bone scan is more sensitive, but lacks specificity. Computerised tomography, magnetic resonance imaging and positron emission tomography all have an increasing role. In treatment-induced osteoporosis, bone mineral density is now readily measured by DEXA scanning. Tumour markers such as CEA, CA 15-3, CA 549 and TPA may have a role in assessing response, but probably in combination rather than individually, using an appropriate quantitative model. Several trials have shown that bone markers, especially markers of bone resorption such as Ntx, Ctx, PYD and DPD, appear to have strong potential as rapid, convenient and inexpensive measures of response. There is also evidence that they may be used as predictive or prognostic indicators. Evidence is accumulating that the reduction of bone resorption markers into the normal range results in substantially reduced morbidity in metastatic breast cancer and that this should be a major target of therapy.

Journal Article↗

A mechanistic approach to the in vivo anti-inflammatory activity of sesquiterpenoid compounds isolated from Inula viscosa.

The present study was designed to examine the anti-inflammatory activity of the sesquiterpenoids ilicic acid and inuviscolide, isolated from Inula viscosa, on cell degranulation, leukotriene biosynthesis, neurogenic drive and glucocorticoid-like interactions. Swiss female mice were used to measure the ear oedema induced by phorbol esters or ethyl phenylpropiolate (EPP), and the paw oedema induced by phospholipase A(2) (PLA(2)) or serotonin. Drug treatment consisted of one topically-applied dose in the ear models and a subcutaneous or intraperitoneal injection in the paw models. Quantitative analysis of leukotriene B(4) (LTB(4)) formation was performed on rat peritoneal neutrophils by high performance liquid chromatography (HPLC). The lactone inuviscolide reduced the PLA(2)-induced oedema (ID(50): 98 micromol/kg). The effect on serotonin-induced oedema was not changed by modifiers of the glucocorticoid response. Ilicic acid showed minor in vivo effects, but was slightly more potent than inuviscolide on the 12-O-tetradecanoylphorbol 13-acetate (TPA) acute oedema test (ID(50): 0.650 micromol per ear). Inuviscolide reduced LTB(4) generation in intact cells, with an IC(50) value of 94 microM. On the basis of the reported results, inuviscolide is the main anti-inflammatory sesquiterpenoid from Inula viscosa, and may act by interfering with leukotriene synthesis and PLA(2)-induced mastocyte release of inflammatory mediators.

Animals↗

Molecular theory of dielectric relaxation in nematic dimers.

This paper reports a theory for the dielectric relaxation of dimeric mesogenic molecules in a nematic liquid crystal phase. Liquid crystal dimers consist of two mesogenic groups linked by a flexible chain. Recent experimental studies [D. A. Dunmur, G. R. Luckhurst, M. R. de la Fuente, S. Diez, and M. A. Perez Jubindo, J. Chem. Phys. 115, 8681 (2001)] of the dielectric properties of polar liquid crystal dimers have found unexpected results for both the static (low frequency) and variable frequency dielectric response of these materials. The theory developed in this paper provides a quantitative model with which to understand the observed experimental results. The mean-square dipole moments of alpha,omega-bis[(4-cyanobiphenyl-4'-yl]alkanes in a nematic phase have been calculated using both the rotational isomeric state model and a full torsional potential for the carbon-carbon bonds of the flexible chain. The orienting effect of the nematic phase is taken into account by a parametrized potential of mean torque acting on the mesogenic groups and the segments in the flexible chain. Results of calculations using the full torsional potential are in excellent agreement with experimental results for comparable systems. The probability density p(eq)(beta(A),beta(B)) for the orientation of the mesogenic groups (A,B) along the nematic director is also calculated. The resultant potential of mean torque is a surface characterized by four deep energy wells or sites equivalent to alignment of the terminal groups A and B approximately parallel and antiparallel to the director; of course, the reversal of the director leads to equivalent sites. This potential energy surface provides the basis for a kinetic model of dielectric relaxation in nematic dimers. Solution of the Fokker-Planck equation corresponding to this four-site model gives the time dependence of the site populations, and hence the time-correlation functions for the total dipole moment along the director. In this model the end-over-end rotation of the molecule, corresponding to simultaneous reversal of both mesogenic groups, is excluded because the activation energy is too large. Results are presented for a number of cases, in which a dipole is located on one or both of the mesogenic groups, and additionally where the groups differ in size. For the latter, under particular conditions, the correlation function exhibits a biexponential decay, which corresponds to two low frequency absorptions in the dielectric spectrum. This is exactly what has been observed for nonsymmetric nematic dimers having different groups terminating a flexible chain. Experimental results over a range of temperature for the nonsymmetric dimer alpha-[(4-cyanobiphenyl)-4'-yloxy]-omega-(4-decylanilinebenzylidene-4'-oxy)nonane can be fitted precisely to the theory, which provides new insight into the orientational and conformational dynamics of molecules in ordered liquid crystalline phases.

Journal Article↗

Acetochlor as a soil pollutant.

Acetochlor is a widely used herbicide all over the world. Similarly to other organic pollutants, the environmental fate of the acetochlor is strongly related to its adsorption properties. Static adsorption equilibrium measurements were carried out at 25 degrees C on different types of Hungarian soils characterized by varying amounts of organic matter and pH values. Isotherms obtained under different conditions, as well as on various soils, exhibit a similar shape, thus indicating a two-step adsorption process. The plots cannot be interpreted according to the classes of isotherms suggested by Giles. The adsorption coefficients (K) were estimated from the initial slope of the curves. These values were determined not only by the type of the soil, but also by the composition of the aqueous media. The organic matter adsorption coefficients (Kom) were also calculated and they were approximately identical for soils of high organic matter. Due to the low value of the adsorption coefficients, the acetochlor is a rather mobile pollutant of the soil posing a potential danger to the aquatic environment. For soils with high organic content, the Kom values are similar to each other and, due to the significant coverage of the inorganic surfaces, the adsorption is controlled by the solute-organic substance interactions. The adsorption of weakly polar compounds, however, is remarkable even on those soils where the organic content is low. In this case, the binding is governed by the solute-inorganic surface interactions. This conclusion is nicely proved by the adsorption of the acetochlor on quartz. According to our hypothesis, the second part of the adsorption step is controlled by the solute-adsorbed solute interactions. The role of the organic matter in this region of the isotherm is probably negligible. As the organic matter content of the soils plays an important role in the acetochlor adsorption, humic substances must have a strong influence upon the transport of this compound. Experiments to obtain adsorption isotherms of further pesticides and the development of a quantitative model are in progress.

Adsorption↗

Facilitatory interactions between flashed lines.

The detectability of pairs of flashed lines was investigated as a joint function of their separation in both space and time. In contrast to previous studies of contrast interactions as a function of either spatial or temporal separation alone, the predominant interaction is not lateral inhibition, but a delayed facilitation. A quantitative model based on probability summation between lateral-inhibitory detectors does not appear able to account for these results. Two related explanations are suggested: either a motion detection system or the nonlinear 'transient' subsystem is being tapped.

Humans↗

Flank transparency: transparent filters seen in dynamic two-color displays.

Flank transparency is the perception of a colored transparent filter evoked by apparent-motion displays containing as few as two colors. Displays of flank transparency contain a random array of line segments placed on a uniform background. Small flanks are added to the line segments if the segments fall in the interior of a moving virtual shape, such as a virtual disk. This leads to the perception of a colored transparent disk with well-defined boundaries moving over the array of lines. Current qualitative and quantitative models of luminance and color conditions for perceptual transparency do not account for flank transparency as they require displays containing at least three different colors.

Color Perception↗