Brain activity during the encoding, retention, and retrieval of stimulus representations

Studies of delayed nonmatching-to-sample (DNMS) performance following lesions of the monkey cortex have revealed a critical circuit of brain regions involved in forming memories and retaining and retrieving stimulus representations. Using event-related functional magnetic resonance imaging (fMRI), we measured brain activity in 10 healthy human participants during performance of a trial-unique visual DNMS task using novel barcode stimuli. The event-related design enabled the identification of activity during the different phases of the task (encoding, retention, and retrieval). Several brain regions identified by monkey studies as being important for successful DNMS performance showed selective activity during the different phases, including the mediodorsal thalamic nucleus (encoding), ventrolateral prefrontal cortex (retention), and perirhinal cortex (retrieval). Regions showing sustained activity within trials included the ventromedial and dorsal prefrontal cortices and occipital cortex. The present study shows the utility of investigating performance on tasks derived from animal models to assist in the identification of brain regions involved in human recognition memory.

Human cortical processing of colour and pattern

The present study investigates human visual processing of simple two-colour patterns using a delayed match to sample paradigm with positron emission tomography (PET). This study is unique in that we specifically designed the visual stimuli to be the same for both pattern and colour recognition with all patterns being abstract shapes not easily verbally coded composed of two-colour combinations. We did this to explore those brain regions required for both colour and pattern processing and to separate those areas of activation required for one or the other. We found that both tasks activated similar occipital regions, the major difference being more extensive activation in pattern recognition. A right-sided network that involved the inferior parietal lobule, the head of the caudate nucleus, and the pulvinar nucleus of the thalamus was common to both paradigms. Pattern recognition also activated the left temporal pole and right lateral orbital gyrus, whereas colour recognition activated the left fusiform gyrus and several right frontal regions. (C) 2001 Wiley-Liss, Inc.

Monocular and binocular distance cues: insights from visual form agnosia I (of III)

The human nervous system constructs a Euclidean representation of near (personal) space by combining multiple sources of information (cues). We investigated the cues used for the representation of personal space in a patient with visual form agnosia (DF). Our results indicated that DF relies predominantly on binocular vergence information when determining the distance of a target despite the presence of other (retinal) cues. Notably, DF was able to construct an Euclidean representation of personal space from vergence alone. This finding supports previous assertions that vergence provides the nervous system with veridical information for the construction of personal space. The results from the current study, together with those of others, suggest that: (i) the ventral stream is responsible for extracting depth and distance information from monocular retinal cues (i.e. from shading, texture, perspective) and (ii) the dorsal stream has access to binocular information (from horizontal image disparities and vergence). These results also indicate that DF was not able to use size information to gauge target distance, suggesting that intact temporal cortex is necessary for learned size to influence distance processing. Our findings further suggest that in neurologically intact humans, object information extracted in the ventral pathway is combined with the products of dorsal stream processing for guiding prehension. Finally, we studied the size-distance paradox in visual form agnosia in order to explore the cognitive use of size information. The results of this experiment were consistent with a previous suggestion that the paradox is a cognitive phenomenon.

Interferon-gamma enhances cytotoxic T lymphocyte recognition of endogenous peptide in keratinocytes without lowering the requirement for surface peptide

Keratinocytes expressing the human papillomavirus (HPV) type 16 E7 protein, as a transgene driven by the K14 promoter, form a murine model of HPV-mediated epithelial cancers in humans. Our previous studies have shown that K14E7 transgenic skin grafts onto syngeneic mice are not susceptible to immune destruction despite the demonstrated presence of a strong, systemic CTL response directed against the E7 protein. Consistent with this finding, we now show that cultured, E7 transgenic keratinocytes (KC) express comparable endogenous levels of E7 protein to a range of CTL-sensitive E7-expressing cell lines but are not susceptible to CTL-mediated lysis in vitro . E7 transgenic and non-transgenic KC are susceptible to conventional mechanisms of CTL-mediated lysis, including perforin and Fas/FasL interaction when an excess of exogenous peptide is provided. The concentration of exogenous peptide required to render a cell susceptible to lysis was similar between KC and other conventional CTL targets (e.g. EL-4), despite large differences in H-2D(b) expression at the cell surface. Furthermore, exposure of KC to IFN-gamma increased H-2D(b) expression, but did not substantially alter the exogenous peptide concentration required to sensitize cells for half maximal lysis. In contrast, the lytic sensitivity of transgenic KC expressing endogenous E7 is modestly improved by exposure to IFN-gamma. Thus, failure of CTL to eliminate KC expressing endogenous E7, and by inference squamous tumours expressing E7, may reflect the need for a sustained, local inflammatory environment during the immune effector phase.

Interaction between natural and sexual selection during the evolution of mate recognition

The interaction between natural and sexual selection is central to many theories of how mate choice and reproductive isolation evolve, but their joint effect on the evolution of mate recognition has not, to my knowledge, been investigated in an evolutionary experiment. Natural and sexual selection were manipulated in interspecific hybrid populations of Drosophila to determine their effects on the evolution of a mate recognition system comprised of cuticular hydrocarbons (CHCs). The effect of natural selection in isolation indicated that CHCs were costly for males and females to produce. The effect of sexual selection in isolation indicated that females preferred males with a particular CHC composition. However, the interaction between natural and sexual selection had a greater effect on the evolution of the mate recognition system than either process in isolation. When natural and sexual selection were permitted to operate in combination, male CHCs became exaggerated to a greater extent than in the presence of sexual selection alone, and female CHCs evolved against the direction of natural selection. This experiment demonstrated that the interaction between natural and sexual selection is critical in determining the direction and magnitude of the evolutionary response of the mate recognition system.

Evolutionary experiments on mate recognition in the Drosophila serrata species complex

It is becoming increasingly apparent that at least some aspects of the evolution of mate recognition may be amenable to manipulation in evolutionary experiments. Quantitative genetic analyses that focus on the genetic consequences of evolutionary processes that result in mate recognition evolution may eventually provide an understanding of the genetic basis of the process of speciation. We review a series of experiments that have attempted to determine the genetic basis of the response to natural and sexual selection on mate recognition in the Drosophila serrata species complex. The genetic basis of mate recognition has been investigated at three levels: (1) between the species of D. serrata and D. birchii using interspecific hybrids, (2) between populations of D. serrata that are sympatric and allopatric with respect to D. birchii, and (3) within populations of D. serrata. These experiments suggest that it may be possible to use evolutionary experiments to observe important events such as the reinforcement of mate recognition, or the generation of the genetic associations that are central to many sexual selection models.

Interspecific variation in plumage colour among birds: species recognition or light environment?

The traditional explanation for interspecific plumage colour variation in birds is that colour differences between species are adaptations to minimize the risk of hybridization. Under this explanation, colour differences between closely related species of birds represent reproductive character displacement. An alternative explanation is that interspecific variation in plumage colour is an adaptive response to variation in light environments across habitats. Under this explanation, differences in colour between closely related species are a product of selection on signal efficiency. We use a comparative approach to examine these two hypotheses, testing the effects of sympatry and habitat use, respectively, on divergence in male plumage colour. Contrary to the prediction of the Species Isolation Hypothesis, we find no evidence that sympatric pairs of species are consistently more divergent in coloration than are allopatric pairs of species. However, in agreement with the Light Environment Hypothesis, we find significant associations between plumage coloration and habitat use. All of these results remain qualitatively unchanged irrespective of the statistical methodology used to compare reflectance spectra, the body regions used in the analyses, or the exclusion of areas of plumage not used in sexual displays. Our results suggest that, in general, interspecific variation in plumage colour among birds is more strongly influenced by the signalling environment than by the risk of hybridization.

Developmental changes in the cone visual pigments of black bream Acanthopagrus butcheri

The spectral absorption characteristics of the visual pigments in the photoreceptors of the black bream Acanthopagrus butcheri Munro (Sparidae, Teleostei), were measured using microspectrophotometry. A single cohort of fish aged 5-172 days post-hatch (dph), aquarium-reared adults and wild-caught juveniles were investigated. During the larval stage and in juveniles younger than 100 dph, two classes of visual pigment were found, with wavelengths of maximum absorbance (lambda(max)) at approximately 425 nm and 535 nm. Following double cone formation, from 40 dph onwards, the short wavelength-sensitive pigment was recorded in single cones and the longer wavelength-sensitive pigment in double cones. From 100 dph, a gradual shift in the lambda(max) towards longer wavelengths was observed in both cone types. By 160 dph, and in adults, all single cones had a lambda(max) at approximately 475 nm while the lambda(max) in double cones ranged from 545 to 575 nm. The relationships between the lambda(max) and the ratio of bandwidth:lambda(max), for changes in either chromophore or opsin, were modelled mathematically for the long-wavelength-sensitive visual pigments. Comparing our data with the models indicated that changes in lambda(max) were not mediated by a switch from an A(1) to A(2) chromophore, rather a change in opsin expression was most likely. The shifts in the lambda(max) of the visual pigments occur at a stage when the juvenile fish begin feeding in deeper, tannin-stained estuarine waters, which transmit predominantly longer wavelengths, so the spectral sensitivity changes may represent an adaptation by the fish to the changing light environment.

Does a reading lexicon provide orthographic representations for spelling?

University students spelled low-frequency words to dictation and subsequently made lexical decisions to them. In Experiment I, lexical decisions were slower on words students had spelled incorrectly relative to words they had spelled correctly, and there A as a larger repetition benefit 101 incorrectly spelled words. In experiment 2, the latency advantage for items spelled correctly was replicated when words were presented for only 200 ms and also in a spelling recognition task, In Experiment 3. masked identity and form priming effects were similar for words that had been spelled correctly and incorrectly, Item spelling accuracy tracked word frequency effects in the way chat it combined with repetition and priming effects. we inter that an individuals learning with a word's orthography underlies word frequency and item spelling accuracy effects and that a single orthographic lexicon serves visual word recognition and spelling. (C) 2000 Elsevier Science (USA).

Enhancing the immunogenicity and modulating the fine epitope recognition of antisera to a helical group A streptococcal peptide vaccine candidate from the M protein using lipid-core peptide technology

A conserved helical peptide vaccine candidate from the M protein of group A streptococci, p145, has been described. Minimal epitopes within p145 have been defined and an epitope recognized by protective antibodies, but not by autoreactive T cells, has been identified. When administered to mice, p145 has low immunogenicity. Many boosts of peptide are required to achieve a high antibody titre (> 12 800). To attempt to overcome this low immunogenicity, lipid-core peptide technology was employed. Lipid-core peptides (LCP) consist of an oligomeric polylysine core, with multiple copies of the peptide of choice, conjugated to a series of lipoamino acids, which acts as an anchor for the antigen. Seven different LCP constructs based on the p145 peptide sequence were synthesized (LCP1-->LCP7) and the immunogenicity of the compounds examined. The most immunogenic constructs contained the longest alkyl side-chains. The number of lipoamino acids in the constructs affected the immunogenicity and spacing between the alkyl side-chains increased immunogenicity. An increase in immunogenicity (enzyme-linked immunosorbent assay (ELISA) titres) of up to 100-fold was demonstrated using this technology and some constructs without adjuvant were more immunogenic than p145 administered with complete Freund's adjuvant (CFA). The fine specificity of the induced antibody response differed for the different constructs but one construct, LCP4, induced antibodies of identical fine specificity to those found in endemic human serum. Opsonic activity of LCP4 antisera was more than double that of p145 antisera. These data show the potential for LCP technology to both enhance immunogenicity of complex peptides and to focus the immune response towards or away from critical epitopes.