Models of face recognition and delusional misidentification: a critical review

The "two-route model of face recognition" proposed by Bauer (1984) and adopted by Ellis and Young (1990), has become a widely accepted model in studies of face processing disorders, including both prosopagnosia and the delusional misidentification syndromes. We review the origin and application of the two-route model of face recognition in examining both the neuroanatomical pathways and the cognitive pathways to face recognition. With respect to the neuroanatomy, we conclude that face recognition is subserved by a single pathway, the ventral visual pathway, as there is no evidence to suggest that the dorsal visual pathway is capable of visual recognition or of providing an affective response to familiar stimuli. We demonstrate how operation of the ventral visual pathway and its connections to the amygdala can parsimoniously account for the findings in the literature on prosopagnosia and delusional misidentification syndromes. In addition, we propose a cognitive model of face processing stemming from the work of Bruce and Young (1986). Our model involves two pathways subsequent to the system responsible for face recognition: one pathway to a system containing semantic and biographical information about the seen face, and a second pathway to a system responsible for the generation of an affective response to faces that are familiar. We demonstrate how this cognitive model can explain the dissociations between overt and covert recognition observed in prosopagnosia and the Capgras delusion.     

102T/C polymorphism of serotonin receptor type 2A gene is not associated with schizophrenia in either Chinese or British populations

Several pieces of evidence implicate serotonin receptors in the aetiology of schizophrenia, and recently a number of studies have reported a genetic association between the 102T/C polymorphism of serotonin receptor type 2A gene and schizophrenia. Unfortunately a number of failures to replicate these positive associations in both Caucasian and Chinese populations have also been reported. We have examined the 102T/C polymorphism by PCR amplification and restriction analysis of DNA from: 202 schizophrenics and 202 controls from Shanghai; 112 schizophrenics and 224 parents from Chengdu, Cina; and 253 schizophrenics and 244 controls from the the UK. We find no evidence of association or transmission disequilibrium between the 102T/C polymorphism and schizophrenia in any of the groups we have examined. We conclude that either the original positive reports occurred by chance or any effect must be minimal, and urge caution in interpreting small positive results derived using data from different centres.     

The search for a marsupial XIC reveals a break with vertebrate synteny

X-chromosome inactivation (XCI) evolved in mammals to deal with X-chromosome dosage imbalance between the XX female and the XY male. In eutherian mammals, random XCI of the soma requires a master regulatory locus known as the ‘X-inactivation center’ (XIC/Xic), wherein lies the noncoding XIST/Xist silencer RNA and its regulatory antisense Tsix gene. By contrast, marsupial XCI is imprinted to occur on the paternal X chromosome. To determine whether marsupials and eutherians share the XIC-driven mechanism, we search for the sequence equivalents in the genome of the South American opossum, Monodelphis domestica. Positional cloning and bioinformatic analysis reveal several interesting findings. First, protein-coding genes that flank the eutherian XIC are well-conserved in M. domestica, as well as in chicken, frog, and pufferfish. However, in M. domestica we fail to identify any recognizable XIST or TSIX equivalents. Moreover, cytogenetic mapping shows a surprising break in synteny with eutherian mammals and other vertebrates. Therefore, during the evolution of the marsupial X chromosome, one or more rearrangements broke up an otherwise evolutionarily conserved block of vertebrate genes. The failure to find XIST/TSIX in M. domestica may suggest that the ancestral XIC is too divergent to allow for detection by current methods. Alternatively, the XIC may have arisen relatively late in mammalian evolution, possibly in eutherians with the emergence of random XCI. The latter argues that marsupial XCI does not require XIST and opens the search for alternative mechanisms of dosage compensation.     

Binding of Streptococcus pyogenes to soluble and insoluble fibronectin.

The interaction of soluble and insoluble fibronectin with Streptococcus pyogenes was investigated. Soluble fibronectin bound to S. pyogenes in a dose-dependent and irreversible manner. Lipoteichoic acid competitively inhibited the binding of fibronectin to S. pyogenes but had little effect on the binding of fibronectin to staphylococci or pneumococci. The phase of growth of the streptococci had a slight effect on binding of fibronectin, with optimal binding occurring in the late log phase. S. pyogenes cells bound to fibronectin immobilized on microtiter plates in a dose-dependent and saturable manner. Both soluble fibronectin and lipoteichoic acid inhibited the binding of streptococci to immobilized fibronectin, suggesting that streptococci interact with soluble and insoluble fibronectin in a similar manner. Antibodies to fibronectin blocked the attachment of streptococci to immobilized fibronectin, whereas normal serum had no effect. Adherence of streptococci to buccal epithelial cells was inhibited by antibodies to fibronectin, but not by normal sera or by antibodies to buccal epithelial cells. The data suggest that lipoteichoic acid on the surface of S. pyogenes binds to fibronectin exposed on the host cell and that such binding mediates the attachment of streptococci to host cells.     

Characterization of lipoteichoic acid binding to polymorphonuclear leukocytes of human blood.

Human polymorphonuclear leukocytes (PMN) were shown to possess specific binding sites for lipoteichoic acid (LTA). LTA binding was reversible and time and temperature dependent. Scatchard plot analysis revealed an apparently single population of 6.6 X 10(6) LTA binding sites per PMN with a dissociation constant of 5.6 microM. Attachment of an avirulent, unencapsulated, M-negative strain of group A streptococci to PMN was inhibited by LTA, but not by other bacterial somatic antigens tested. Occupation of 30% of the LTA binding sites resulted in greater than 70% inhibition of streptococcal attachment to PMN. In contrast, LTA failed to block attachment of Escherichia coli or antibody-coated streptococci, indicating that binding sites for E. coli and the Fc portion of immunoglobulin G are distinct from those for LTA. Immunofluorescent studies demonstrated that LTA remained uniformly bound to PMN membranes for as long as 2 h at 37 degrees C. Cross-linking of PMN-bound LTA with anti-LTA resulted in rapid capping of LTA receptor sites. The results suggest that LTA is a monovalent ligand interacting with mobile receptors in the plasma membrane of PMN.     

Thymocyte expression of cathepsin L is essential for NKT cell development

CD1d antigen presentation to natural killer T (NKT) cells expressing the semi-invariant T cell receptor V(alpha)14J(alpha)18 requires CD1d trafficking through endosomal compartments; however, the endosomal events remain undefined. We show that mice lacking the endosomal protease cathepsin L (catL) have greatly reduced numbers of V(alpha)14(+)NK1.1(+) T cells. In addition, catL expression in thymocytes is critical not only for selection of these cells in vivo but also for stimulation of V(alpha)14(+)NK1.1(+) T cells in vitro. CD1d cell-surface expression and intracellular localization appear normal in catL-deficient thymocytes, as does the lysosomal morphology; this implies a specific role for catL in regulating presentation of natural CD1d ligands mediating V(alpha)14(+)NK1.1(+) T cell selection. These data implicate lysosomal proteases as key regulators of not only classical major histocompatibility complex class II antigen presentation but also nonclassical CD1d presentation.     

Isolation and characterization of a large molecular-weight polypeptide of herpes simplex virus type 1

Infection of human embryonic lung cells at the nonpermissive temperature (39°) with tsB2, a DNA-negative mutant of herpes simplex virus type 1 (HSV-1) resulted in the accumulation of a large molecular-weight (175,000) virus-induced polypeptide detectable by SDS-polyacrylamide gel electrophoresis. This polypeptide (VP175) was detectable only in small amounts and was found mainly in the nuclear fraction of cells infected with tsB2 at the permissive temperature (34°) or with wild-type HSV-1 at both 34° and 39°. However at 39° VP175 accumulated to become the major component in both the cytoplasmic and nuclear fractions of tsB2-infected cells. Identical results were obtained with a second mutant (tsB21) in the same complementation group. Temperature-shift studies suggest that the events responsible for the accumulation of VP175 at 39° occur early in the replicative cycle. With the use of a combination of SDS-preparative and analytical disc gel electrophoresis, VP175 was isolated and rabbit antisera to this polypeptide were prepared. By immunofluorescence assay, anti-VP175 sera reacted only with the nucleus of wild-type HSV-1-infected cells, whereas tsB2-infected cells cultured at 39° showed both cytoplasmic and nuclear immunofluorescence. In addition, the anti-VP175 serum reacted preferentially with HSV-1 as compared with HSV-2-infected cells, suggesting a possible type specificity for the reagent.