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Unprecedented chiral molecular recognition in a C3-symmetric environment.

The enantiomeric recognition of alpha-chiral primary ammonium ions has been studied with benzene-based tripodal tris(oxazoline) receptors. Contrary to the literature and our expectation, a good level of chiral discrimination is observed with one of the tripodal receptors, which provides a C3-symmetric chiral environment on guest binding. The chiral discrimination has been found to be general in the case of alpha-aryl substituted guests, suggesting pi-pi interactions as an important factor. This result raises a question with respect to the origin of the chiral discrimination since little steric or electronic difference is expected between the diastereomeric inclusion complexes. Binding studies by NMR titration and isothermal titration calorimetry show that the chiral discrimination results from the different thermodynamic stabilities between the diastereomeric complexes and that the host-guest complex formation is driven by favorable enthalpy changes with a minor negative contribution by entropy changes. The X-ray crystal structures for both of the diastereomeric inclusion complexes are resolved, which unambiguously show the binding mode and provide clues on the origin of the chiral discrimination. Bond angle analyses indicate that the minor complex experiences a larger steric strain, which is discernible when it is viewed from "three-body" interactions between the host and the guest. The guest and oxazoline phenyl rings are well stacked, indicating interplay of the pi-pi interactions. The pi-pi interactions are believed to stabilize host-guest complexes, thereby endowing the highly flexible receptors with a substantial enantio-discrimination.

Crystallography, X-Ray↗

NFI and Oct-1 bend the Ad5 origin in the same direction leading to optimal DNA replication.

Two cellular transcription factors, nuclear factor I (NFI) and octamer binding protein (Oct-1), bind simultaneously to their recognition sequences in the Ad5 origin of replication thereby enhancing initiation. Using scanning force microscopy we have previously shown that NFI induces a 60 degrees bend in the origin DNA. Here we demonstrate that Oct-1 induces a 42 degrees bend in the origin DNA. Simultaneous binding of NFI and Oct-1 induces an 82 degrees collective bend suggesting that both bends are oriented towards each other. In functional replication assays we further demonstrate that this extensive DNA bending leads to a synergistic enhancement of DNA replication. We propose that collective DNA bending induced by NFI and Oct-1 facilitates the optimal assembly of the preinitiation complex and plays an important role in the stimulatory mechanism of NFI and Oct-1 in replication.

Adenoviridae↗

Emergent modes of work and communities of practice.

This paper argues that the recent emphasis on teams in the health services research literature tends to be attributed to our rising recognition that flexible and self-organizing teams are in the best position to handle the increasing complexity and fragmentation of health services. With a brief review of two papers on health-care teams as its point of departure, this paper argues that the concern with teams harbours a realization that the organizational-managerial point of gravity of most clinical work lies with those who do the work. In the context of health reforms sweeping across most countries in the industrialized world, this means that teams are to embody dynamic self-organization as do 'communities of practice (CoPs)', and be the origin of the managerial and documentary realities that describe, define and validate them. Following through on this last point, the paper reflects on some of the constitutive facets of teams as CoPs, and proposes that in the context of health reform such emergent teamness encompass participating, knowledging and boundary spanning. Fusing contextual, attributional and processual dimensions of team conduct, these notions are elaborated to show how descriptions of teamness can be rendered sensitive to the prerogatives of health reform. The paper concludes with outlining some of the implications of this proposal for how we reconceptualize health services management.

Australia↗

Characterization by NMR and molecular modeling of the binding of polyisoprenols and polyisoprenyl recognition sequence peptides: 3D structure of the complexes reveals sites of specific interactions.

The objective of these studies was to test the hypothesis that proteins that contain potential polyisoprenyl recognition sequences (PIRSs) in their transmembrane-spanning domain can bind to the polyisoprenyl (PI) glycosyl carrier lipids undecaprenyl phosphate (C55-P) and dolichyl phosphate (C95-P). A number of prokaryotic and eukaryotic glycosyltransferases that utilize PI coenzymes contain a conserved PIRS postulated to be the active PI binding domain. To study this problem, we first determined the 3D structure of a PIRS peptide, NeuE, by homonuclear 2D 1H-nuclear magnetic resonance (NMR) spectroscopy. Experimentally generated distance constraints derived from nuclear Overhauser enhancement and torsion angle constraints derived from coupling constants were used for restrained molecular dynamics and energy minimization calculations. Molecular models of the NeuE peptide were built based on calculations of energy minimization using the DGII program NMRchitect. 3D models of dolichol (C95) and C95-P were built based on our 2D 1H-NMR nuclear Overhauser enhancement spectroscopy (NOESY) results and refined by energy minimization with respect to all atoms using the AMBER (assisted modeling with energy refinements) force field. Our energy minimization studies were carried out on a conformational model of dolichol that was originally derived from small-angle X-ray scattering and molecular mechanics methods. These results revealed that the PIs are conformationally nearly identical tripartite molecules, with their three domains arranged in a coiled, helical structure. Analyses of the intermolecular cross-peaks in the 2D NOESY spectra of PIRS peptides in the presence of PIs confirmed a highly specific interaction and identified key contact amino acids in the NeuE peptide that constituted a binding motif for interacting with the PIs. These studies also showed that subtle conformational changes occurred within both the PIs and the NeuE peptide after binding. 3D structures of the resulting molecular complexes revealed that each PI could bind more than one PIRS peptide. These studies thus represent the first evidence for a direct physical interaction between specific contact amino acids in the PIRS peptides and the PIs and supports the hypothesis of a bifunctional role for the PIs. The central idea is that these superlipids may serve as a structural scaffold to organize and stabilize in functional domains PIRS-containing proteins within multiglycosyltransferase complexes that participate in biosynthetic and translocation processes.

Amino Acid Sequence↗

Highly efficient tandem affinity purification of trypanosome protein complexes based on a novel epitope combination.

Tandem affinity purification (TAP) allows for rapid and efficient purification of epitope-tagged protein complexes from crude extracts under native conditions. The method was established in yeast and has been successfully applied to other organisms, including mammals and trypanosomes. However, we found that the original method, which is based on the TAP tag, consisting of a duplicate protein A epitope, a tobacco etch virus protease cleavage site, and the calmodulin-binding peptide (CBP), did not yield enough recovery of transcription factor SNAPc (for small nuclear RNA-activating protein complex) from crude trypanosome extracts for protein identification. Specifically, the calmodulin affinity chromatography step proved to be inefficient. To overcome this problem, we replaced CBP by the protein C epitope (ProtC) and termed this new epitope combination PTP tag. ProtC binds with high affinity to the monoclonal antibody HPC4, which has the unique property of requiring calcium for antigen recognition. Thus, analogous to the calcium-dependent CBP-calmodulin interaction, ProtC-tagged proteins can be released from immobilized HPC4 by a chelator of divalent cations. While this property was retained, epitope substitution improved purification in our experiments by eliminating the inefficiency of calmodulin affinity chromatography and by providing an alternative way of elution using the ProtC peptide in cases where EGTA inactivated protein function. Furthermore, HPC4 allowed highly sensitive and specific detection of ProtC-tagged proteins after protease cleavage. Thus far, we have successfully purified and characterized the U1 small nuclear ribonucleoprotein particle, the transcription factor complex TATA-binding protein related factor 4 (TRF4)/SNAPc/transcription factor IIA (TFIIA), and RNA polymerase I of Trypanosoma brucei.

Animals↗

Open Set face recognition using transduction.

This paper motivates and describes a novel realization of transductive inference that can address the Open Set face recognition task. Open Set operates under the assumption that not all the test probes have mates in the gallery. It either detects the presence of some biometric signature within the gallery and finds its identity or rejects it, i.e., it provides for the "none of the above" answer. The main contribution of the paper is Open Set TCM-kNN (Transduction Confidence Machine-k Nearest Neighbors), which is suitable for multiclass authentication operational scenarios that have to include a rejection option for classes never enrolled in the gallery. Open Set TCM-kNN, driven by the relation between transduction and Kolmogorov complexity, provides a local estimation of the likelihood ratio needed for detection tasks. We provide extensive experimental data to show the feasibility, robustness, and comparative advantages of Open Set TCM-kNN on Open Set identification and watch list (surveillance) tasks using challenging FERET data. Last, we analyze the error structure driven by the fact that most of the errors in identification are due to a relatively small number of face patterns. Open Set TCM-kNN is shown to be suitable for PSEI (pattern specific error inhomogeneities) error analysis in order to identify difficult to recognize faces. PSEI analysis improves biometric performance by removing a small number of those difficult to recognize faces responsible for much of the original error in performance and/or by using data fusion.

Algorithms↗

Direct binding of a synthetic multichain polypeptide to class II major histocompatibility complex molecules on antigen-presenting cells and stimulation of a specific T-cell line require processing of the polypeptide.

T-cell activation involves the recognition of foreign antigens as a complex with self-major histocompatibility complex (MHC) proteins on the surface of antigen-presenting cells (APC). Protein antigens usually require uptake by the APC and processing that results in the generation of peptide fragments. The branched synthetic polypeptide (Tyr, Glu)-Ala--Lys was chosen as a model antigen to follow the processing requirements, leading to T-cell activation. It has been demonstrated, by using fixed APC and various inhibitors of proteases, that (Tyr, Glu)-Ala--Lys has to be processed to stimulate a (Tyr, Glu)-Ala--Lys-specific T-cell line of C3H.SW (H-2b) origin to proliferate. To determine whether processing of (Tyr,Glu)-Ala--Lys is required to allow its association with the MHC class II molecules, biotin was covalently attached to it. Binding of the biotinylated (Tyr,Glu)-Ala--Lys to MHC class II gene products on the surface of intact normal APC was directly detected by phycoerythrin-streptavidin. The specificity of the binding was confirmed by its inhibition with anti-I-Ab antibodies as well as with excess of nonlabeled (Tyr,Glu)-Ala--Lys. Furthermore, introducing several inhibitors of proteases to the binding assay, we could substantiate that the proteolysis of (Tyr,Glu)-Ala--Lys is required to allow association of the resulting peptidyl T-cell epitopes with the MHC class II molecules themselves. The presence of the biotin moiety in the resulting peptides suggests that the T-cell epitopes of (Tyr,Glu)-Ala--Lys contain the N-terminal portion of the side chains of the branched polypeptide. An apparent Kd of 8.05 x 10(-8) M was determined, and optimal binding was detected after 10 hr of incubation with the antigen. The latter phenomenon is not due to slow uptake, since uptake of (Tyr,Glu)-Ala--Lys occurs mainly during the first 30 min of incubation, but rather reflects the events of processing that precede MHC interaction.

Animals↗

Structure-based prediction of binding peptides to MHC class I molecules: application to a broad range of MHC alleles.

Specific binding of antigenic peptides to major histocompatibility complex (MHC) class I molecules is a prerequisite for their recognition by cytotoxic T-cells. Prediction of MHC-binding peptides must therefore be incorporated in any predictive algorithm attempting to identify immunodominant T-cell epitopes, based on the amino acid sequence of the protein antigen. Development of predictive algorithms based on experimental binding data requires experimental testing of a very large number of peptides. A complementary approach relies on the structural conservation observed in crystallographically solved peptide-MHC complexes. By this approach, the peptide structure in the MHC groove is used as a template upon which peptide candidates are threaded, and their compatibility to bind is evaluated by statistical pairwise potentials. Our original algorithm based on this approach used the pairwise potential table of Miyazawa and Jernigan (Miyazawa S, Jernigan RL, 1996, J Mol Biol 256:623-644) and succeeded to correctly identify good binders only for MHC molecules with hydrophobic binding pockets, probably because of the high emphasis of hydrophobic interactions in this table. A recently developed pairwise potential table by Betancourt and Thirumalai (Betancourt MR, Thirumalai D, 1999, Protein Sci 8:361-369) that is based on the Miyazawa and Jernigan table describes the hydrophilic interactions more appropriately. In this paper, we demonstrate how the use of this table, together with a new definition of MHC contact residues by which only residues that contribute exclusively to sequence specific binding are included, allows the development of an improved algorithm that can be applied to a wide range of MHC class I alleles.

Alleles↗

Familiarity, spatial frequency and task determinants in processing laterally presented representations of faces.

Laterally presented portraits were judged as familiar or unfamiliar (Experiments 1 and 2), or were processed in a target matching task (Experiment 3). Exposure durations (100 or 190 msec.) were varied between (Experiments 1 and 2) or within (Experiment 3) the experiments. Clear and degraded faces appeared either randomly intermingled (Experiment 1) or in blocked sequences (Experiments 2 and 3). In Experiment 3 familiar and unfamiliar stimuli also appeared in blocks. Stimulus degradation was achieved by coarse quantization of the image into blocks, so replacing relevant high-spatial-frequencies (the features) by spurious information, preserving only the original lower-spatial-frequency components. Left hemisphere mediation was strongest and most consistent with long exposures and random sequences of clear and degraded stimuli. Right hemisphere mediation tended to appear with shorter exposures and degraded stimuli presented in blocks. Though the interactions were often complex, the general pattern of results was consistent with the analytic-holistic processing dichotomy.

Discrimination Learning↗

Helix bending as a factor in protein/DNA recognition.

Normal vectors perpendicular to individual base pairs are a powerful tool for studying the bending behavior of B-DNA, both in the form of normal vector plots and in matrices that list angles between vectors for all possible base pair combinations. A new analysis program, FREEHELIX, has been written for this purpose, and applied to 86 examples of sequence-specific protein/DNA complexes whose coordinates are on deposit in the Nucleic Acid Data Base. Bends in this sample of 86 structures almost invariably follow from roll angles between adjacent base pairs; tilt makes no net contribution. Roll in a direction compressing the broad major groove is much more common than that which compresses the minor groove. Three distinct types of B-DNA bending are observed, each with a different molecular origin: (1) Localized kinking is produced by large roll at single steps or at two steps separated by one turn of helix. (2) Smooth, planar curvature is produced by positive and negative roll angles spaced a half-turn apart, with random side-to-side zigzag roll at intermediate points, rather than a tilt contribution that might have been expected theoretically. (3) Three-dimensional writhe results from significant roll angles at a continuous series of steps. Writhe need not change the overall direction of helix axis, if it is continued indefinitely or for an integral number of helical turns. A-DNA itself can be formally considered as possessing uniform, continuous writhe that yields no net helix bending. Smooth curvature is the most intricate deformation of the three, and is least common. Writhe is the simplest deformation and is most common; indeed, a low level of continuous writhe is the normal condition of an otherwise unbent B-DNA helix of general sequence. With one exception, every example of major kinking in this sample of 86 structures involves a pyrimidine-purine step: C-A/T-G, T-A, or C-G. Purine-purine steps, especially A-A, show the least tendency toward roll deformations.

Animals↗

Thermodynamics of aminoglycoside-rRNA recognition: the binding of neomycin-class aminoglycosides to the A site of 16S rRNA.

We use spectroscopic and calorimetric techniques to characterize the binding of the aminoglycoside antibiotics neomycin, paromomycin, and ribostamycin to a RNA oligonucleotide that models the A-site of Escherichia coli 16S rRNA. Our results reveal the following significant features: (i) Aminoglycoside binding enhances the thermal stability of the A-site RNA duplex, with the extent of this thermal enhancement decreasing with increasing pH and/or Na(+) concentration. (ii) The RNA binding enthalpies of the aminoglycosides become more exothermic (favorable) with increasing pH, an observation consistent with binding-linked protonation of one or more drug amino groups. (iii) Isothermal titration calorimetry (ITC) studies conducted as a function of buffer reveal that aminoglycoside binding to the host RNA is linked to the uptake of protons, with the number of linked protons being dependent on pH. Specifically, increasing the pH results in a corresponding increase in the number of linked protons. (iv) ITC studies conducted at 25 and 37 degrees C reveal that aminoglycoside-RNA complexation is associated with a negative heat capacity change (Delta C(p)), the magnitude of which becomes greater with increasing pH. (v) The observed RNA binding affinities of the aminoglycosides decrease with increasing pH and/or Na(+) concentration. In addition, the thermodynamic forces underlying these RNA binding affinities also change as a function of pH. Specifically, with increasing pH, the enthalpic contribution to the observed RNA binding affinity increases, while the corresponding entropic contribution to binding decreases. (vi) The affinities of the aminoglycosides for the host RNA follow the hierarchy neomycin > paromomycin > ribostamycin. The enhanced affinity of neomycin relative to either paromomycin or ribostamycin is primarily, if not entirely, enthalpic in origin. (vii) The salt dependencies of the RNA binding affinities of neomycin and paromomycin are consistent with at least three drug NH(3)(+) groups participating in electrostatic interactions with the host RNA. In the aggregate, our results reveal the impact of specific alterations in aminoglycoside structure on the thermodynamics of binding to an A-site model RNA oligonucleotide. Such systematic comparative studies are critical first steps toward establishing the thermodynamic database required for enhancing our understanding of the molecular forces that dictate and control aminoglycoside recognition of RNA.

Anti-Bacterial Agents↗

Cystic malformations of the posterior cranial fossa originating from a defect of the posterior membranous area. Mega cisterna magna and persisting Blake's pouch: two separate entities.

Cystic malformations of the posterior cranial fossa are all but arachnoid cysts contained within the general context of the Dandy-Walker complex and may be further classified in two groups on the basis of their embryological origin: anomalies of the anterior membranous area (AMA) and anomalies of the posterior membranous area (PMA). Whether the latter group of malformations can be regarded as separate entities is still quite controversial. The present authors give a detailed account of the various embryological stages in the formation of the posterior cranial fossa and its contents and propose the identification of two anomalies derived from a defect of the PMA: the mega cisterna magna (MCM) and the persisting Blake's pouch, a new entity with different MRI features from MCM. Criteria for their recognition are discussed, stressing the capital importance of a differential diagnosis in view of the radically different therapeutic approach.

Arachnoid Cysts↗

Strategy of macromolecular grafting onto a gold substrate dedicated to protein-protein interaction measurements.

Many biotechnology applications use proteins immobilized on surface. For biosensor, the sensing layer is a key component interfacing the transducer and the sample. Strategies employed to activate the bidimensional surface act directly on the performance of the biosensor. In this paper we propose a novel strategy for engineered proteins self-assembly. Our original supramolecular structure allows a direct and fast covalent attachment of proteins onto bare gold substrate through a homobifunctional cross-linker, 1,4-di-([2'-pyridyldithio]propionamido)butane (DPDPB). In this work, engineered proteins and linker-protein complexes were synthesized and characterized by gel electrophoresis, chromatography and spectroscopy experiments. Macromolecular construction "DPDPB-GST tag-GEC1 protein" was conceived in order to guarantee a 2D architecture enhancing the capabilities of the target (tubulin) to recognize its partner (GEC1). Surface plasmon resonance measurements clearly showed potential of this particular self-assembled protein layer compared to a commercial immunosensor interface. At the concentrations tested, the recognition process occurs between tubulin and the immobilized GEC1; moreover enhanced binding was obtained with the home-made 2D sensing layer more than with 3D carboxymethyl dextran matrix.

Biosensing Techniques↗

Structural basis for removal of adenine mispaired with 8-oxoguanine by MutY adenine DNA glycosylase.

The genomes of aerobic organisms suffer chronic oxidation of guanine to the genotoxic product 8-oxoguanine (oxoG). Replicative DNA polymerases misread oxoG residues and insert adenine instead of cytosine opposite the oxidized base. Both bases in the resulting A*oxoG mispair are mutagenic lesions, and both must undergo base-specific replacement to restore the original C*G pair. Doing so represents a formidable challenge to the DNA repair machinery, because adenine makes up roughly 25% of the bases in most genomes. The evolutionarily conserved enzyme adenine DNA glycosylase (called MutY in bacteria and hMYH in humans) initiates repair of A*oxoG to C*G by removing the inappropriately paired adenine base from the DNA backbone. A central issue concerning MutY function is the mechanism by which A*oxoG mispairs are targeted among the vast excess of A*T pairs. Here we report the use of disulphide crosslinking to obtain high-resolution crystal structures of MutY-DNA lesion-recognition complexes. These structures reveal the basis for recognizing both lesions in the A*oxoG pair and for catalysing removal of the adenine base.

Adenine↗

Alteration of sequence specificity of the type II restriction endonuclease HincII through an indirect readout mechanism.

The functional and structural consequences of a mutation of the DNA intercalating residue of HincII, Q138F, are presented. Modeling has suggested that the DNA intercalation by Gln-138 results in DNA distortions potentially used by HincII in indirect readout of its cognate DNA, GTYRAC (Y = C or T, R = A or G) (Horton, N. C., Dorner, L. F., and Perona, J. J. (2002) Nat. Struct. Biol. 9, 42-47). Kinetic data presented here indicate that the mutation of glutamine 138 to phenylalanine (Q138F) results in a change in sequence specificity at the center two base pairs of the cognate recognition site. We show that the preference of HincII for cutting, but not binding, the three cognate sites differing in the center two base pairs has been altered by the mutation Q138F. Five new crystal structures are presented including Q138F HincII bound to GTTAAC and GTCGAC both with and without Ca2+ as well as the structure of wild type HincII bound to GTTAAC. The Q138F HincII/DNA structures show conformational changes in the protein, bound DNA, and at the protein-DNA interface, consistent with the formation of adaptive complexes. Analysis of these structures and the effect of Ca2+ binding on the protein-DNA interface illuminates the origin of the altered specificity by the mutation Q138F in the HincII enzyme.

Amino Acid Substitution↗

Multidetector-row computed tomography angiography for planning intra-arterial chemotherapy pump placement in patients with colorectal metastases to the liver.

PURPOSE: The purpose of this study was to evaluate the use of multidetector computed tomography (MDCT) in the preoperative arterial evaluation of patients scheduled to undergo intra-arterial chemotherapy pump placement. METHODS: Computed tomography scans of 30 patients with hepatic malignancies who were imaged with multiphase MDCT angiography for intra-arterial chemotherapy pump placement were retrospectively analyzed. Dual-phase helical CT was performed, and the arterial phase images were processed to depict the arterial anatomy and to identify pertinent anomalies. All findings were compared and correlated with surgical findings or catheter angiography if surgery was contraindicated. RESULTS: Arterial anomalies identified on CT angiography in 20 of 30 patients included a replaced right hepatic artery (RHA; n = 6) or left hepatic artery (LHA; n = 8), a replaced common hepatic artery (n = 1), an accessory RHA (n = 2) or LHA (n = 6), a replaced gastroduodenal artery (GDA; n = 2), an extrahepatic connection between the accessory RHA and the replaced RHA (n = 1), and a common origin composed of the GDA and RHA and LHA (n = 2). There were no additional arteries or anomalies identified by catheter angiography, when available, or during surgery. Only 1 variant, an accessory hepatic artery, was not located during surgery. In 2 patients, the surgical team decided that pump placement was not feasible because of overly complex anatomy as determined by CT angiography. Computed tomography angiography showed an overall sensitivity of 100% and specificity of 97%. CONCLUSIONS: Multidetector computed tomography angiography is accurate for the preoperative evaluation of normal and aberrant hepatic vasculature in patients under consideration for intra-arterial chemotherapy pump placement. Axial images alone permit recognition of vascular anomalies, including complex anatomy. Nevertheless, 3-dimensional rendering is useful to evaluate complex vascular anatomy and does not require catheter angiographic confirmation. In addition to aiding in selecting patients ideal for pump placement, MDCT permits noninvasive planning of their surgical approach.

Aged↗

Incest perpetrators. Their assessment and treatment.

The multitude of articles published in the last decade in the area of intrafamilial sexual abuse highlight the complexity of the issue--both its assessment and treatment. Although no unique profile of an incest perpetrator exists, a review of studies revealed problems in the areas of sexual satisfaction, psychological functioning, interpersonal relationships, and family of origin. As well, incest families have been reported to be dysfunctional, with power imbalances; control struggles; indirect, unclear communication; and inappropriate coalitions among family members. Based on these observations, a wide range of treatment interventions now exists, including offender-oriented cognitive/behavioral therapies and a family-focused multimodal systems approach. Although questions remain to be answered in regard to the effectiveness and process of treatment, efforts limited to the recognition of these problematic families are no longer adequate. The focus must move to prevention through the early identification of individuals at risk both for offending and being part of an incest family structure; the implementation of proven, cost-effective, proactive intervention strategies; and the continuing dissemination of information to the public.

Adolescent↗

Primary visual cortex and memory. Retinal position specificity and lack of size constancy at early stages of learning a visual memory task in the macaque.

Two monkeys were trained in a novel version of a delayed match-to-sample (DMS) task. They were required to fixate on a small spot at the center of the monitor and distinguish whether two gratings presented one after the other with delays up to 1.5 s in a specific visual field location were similar or not. It was found that such learning fails to transfer readily to other retinal locations. In fact, the learning was sensitive even to very small retinal displacements of the visual stimuli. Such acute retinal position specificity implies that at least a component of the learning in this particular memory task occurs at an early visual area such as the striate cortex, which has a fine-grain topographical representation. Furthermore, at early stages of learning the DMS task, when the monkeys had not generalized the learning to stimuli of different sizes, they failed to show size constancy. That is, when the display was placed at a different distance but with the same absolute size, the performance dropped. The performance was almost fully restored when, at the new display location, stimuli were changed to fit the original retinal size. This indicates that a crucial component of the learning does occur at a site even prior to size constancy. These results show that, under certain situations, an early visual area such as the primary visual cortex may be involved even in complex behaviours such as a memory task as more than just a feature-detecting area or a relay station.

Animals↗