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Neural basis of shape representation in the primate brain.

Visual shape recognition--the ability to recognize a wide variety of shapes regardless of their size, position, view, clutter and ambient lighting--is a remarkable ability essential for complex behavior. In the primate brain, this depends on information processing in a multistage pathway running from primary visual cortex (V1), where cells encode local orientation and spatial frequency information, to the inferotemporal cortex (IT), where cells respond selectively to complex shapes. A fundamental question yet to be answered is how the local orientation signals (in V1) are transformed into selectivity for complex shapes (in IT). To gain insights into the underlying mechanisms we investigated the neural basis of shape representation in area V4, an intermediate stage in this processing hierarchy. Theoretical considerations and psychophysical evidence suggest that contour features, i.e. angles and curves along an object contour, may serve as the basis of representation at intermediate stages of shape processing. To test this hypothesis we studied the response properties of single units in area V4 of primates. We first demonstrated that V4 neurons show strong systematic tuning for the orientation and acuteness of angles and curves when presented in isolation within the cells' receptive field. Next, we found that responses to complex shapes were dictated by the curvature at a specific boundary location within the shape. Finally, using basis function decoding, we demonstrated that an ensemble of V4 neurons could successfully encode complete shapes as aggregates of boundary fragments. These findings identify curvature as a basis of shape representation in area V4 and provide insights into the neurophysiological basis for the salience of convex curves in shape perception.

Animals↗

Gene transfer into primates and prospects for gene therapy in humans.

Retroviral vectors infect primate bone marrow cells and express in vivo the transferred genes (the human ADA gene and the bacterial gene for neomycin resistance). The SAX vector appears to express human ADA at normal levels, but the infection efficiency is low (less than 1%) so that the gene product is only detectable in the peripheral blood at low levels. Vector expression disappears after 5 months (except for occasional T cells), presumably due to a failure to infect a renewal stem cell. While the level of ADA expression obtained in primates would not appear to be sufficient to correct outright the disease caused by ADA deficiency, it is possible that T-cell progenitors in the marrow will have a selective advantage. T cells expressing an ADA vector would then able to expand and potentially restore immune function. Unfortunately, this hypothesis will go untested until an animal model for ADA deficiency is found or a human clinical trial is performed. At present, consideration of gene therapy as a treatment for ADA deficiency would only be appropriate if all conventional forms of treatment were unsuccessful. If such a scenario should present itself, the critical question becomes one of safety, to both the patient and those in contact with the patient. We have begun to address the safety issues associated with gene therapy. Five animals exposed to replication-competent retrovirus during bone marrow transplantation show no evidence of helper virus, with a mean follow-up of 18.3 months. Four animals injected with replication-competent helper virus cleared the virus rapidly and, after the initial clearance, have shown no evidence of retroviremia, with a mean follow-up of 5.2 months. Our preliminary findings suggest that murine retorviruses do not cause a productive infection in vivo. These results, combined with the availability of better producer cell lines free of helper virus, are encouraging, and suggest that the risk of clinical disease from murine retrovirus introduced by a gene therapy protocol should be small. Unfortunately, high infection efficiency and long-term vector expression still must be obtained before retroviral-mediated gene transfer can be considered as first-line therapy for ADA deficiency.

Animals↗

Conservation in decay accelerating factor (DAF) structure among primates.

The decay accelerating factor (DAF, CD55) protects self cells from activation of autologous complement on their surfaces. It functions to disable the C3 convertases, the central amplification enzymes of the cascade. Its active site(s) are contained within four approximately 60 amino acid long units, termed complement control protein repeats (CCPs), which are suspended above the cell surface on a 68 amino acid long serine/threonine (S/T)-rich cushion that derives from three exons. We previously proposed a molecular model of human DAF's four CCPs in which certain amino acids were postulated to be recognition sites for the interaction between DAF and the C3 convertases. In the current study, we characterized DAF in five non-human primates: the great apes, gorilla and common chimpanzee, and the Old World monkeys: hamadryas baboon, Rhesus macaque, and patas monkey. Amino acid homology to human DAF was approximately 98% for the two great apes and 83% for the three Old World monkeys. The above cited putative ligand interactive residues were found to be fully conserved in all of the non-human primates, although there were amino acid changes outside of these areas. In the chimpanzee, alternative splicing of the S/T region was found potentially to be the source of multiple protein isoforms in erythrocytes, whereas in the patas monkey, similar alternative splicing was observed but only one protein band was seen. Interestingly, a Rhesus macaque was found to exhibit a phenomenon paralleling the human Cromer Dr(a-) blood group, in which a 44-base pair deletion in CCP3 leads to a frameshift and early STOP codon.

Alternative Splicing↗

Social influences on endocrine activity in guinea pigs, with comparisons to findings in nonhuman primates.

Guinea pigs exhibit a rich and varied social organization. Studies in recent years have demonstrated that social stimuli have widespread neuroendocrine effects in guinea pigs. Here, effects on the hypothalamic-pituitary-adrenal, adrenal medullary/sympathetic, and hypothalamic-pituitary-gonadal systems of both adult and developing guinea pigs are reviewed. These systems respond to various social variables, or factors that affect social variables, including: separation from attachment objects, housing conditions, changes in housing, the familiarity of the environment in which social interactions occur, foraging conditions, surrogate-rearing, agonistic interactions, and the establishment of dominance rank. Similarities and differences between these findings and those in nonhuman primates are discussed. It is argued that the guinea pig is well suited for the study of socioendocrine effects throughout the life span, and can provide a valuable complement to nonhuman primate research in this area.

Animals↗

How are immune complexes bound to the primate erythrocyte complement receptor transferred to acceptor phagocytic cells?

Immune complexes (IC) bound to the primate erythrocyte (E) complement receptor (CR1) are cleared from the circulation of primates and localized to phagocytic cells in the liver and spleen without E destruction. IC can be bound to E CRI either via C3b opsonization or with cross-linked mAb complexes (heteropolymers, HP) which contain a mAb specific for CRI and a mAb specific for an antigen. The long-term goal of our work is to apply the HP system to the treatment of human diseases associated with blood-borne pathogens. This review discusses the mechanism by which the E-bound IC are transferred to acceptor cells. Our studies in animal models as well as our in vitro investigations indicate that IC transfer is rapid (usually >90% in 10 min) and does not lead to lysis or phagocytosis of the E. Experiments with specific inhibitors and the use of IC prepared with Fab' fragments suggest that transfer depends mainly upon recognition by Fc receptors on the acceptor cell. Moreover, we find that IC release from the E is associated with a concerted loss of CR1, and is followed by uptake and internalization of the IC by the acceptor cell. We suggest that recognition and binding of the E-bound IC substrates by Fc receptors allows close contact between the E and acceptor cells, which in turn facilitates proteolysis of E CR1, presumably by a macrophage-associated protease. After proteolysis, the released IC are internalized by the macrophages.

Animals↗

Immunological response in the primate oviduct to a defined recombinant sperm immunogen.

Assessment of immune responses in the oviduct is of importance in understanding reproductive tract responses to infections, vaccination against reproductive tract pathogens, or contraceptive immunogens. This review discusses a technique that permits repeated sampling of oviductal fluid from the same monkey at intervals spanning up to several years, and the analysis of antigen-specific immunoglobulins in the fluid. This technique is important to immunocontraceptive development because previous studies in primates have lacked information on oviductal immune responses and contraceptive efficacy may not correlate well with serum antibody titers. Thus, a reliable method of sampling oviductal fluid before and after immunization with a defined antigen is required to determine the quantity and type of local immune responses necessary to achieve contraceptive effects. Implantation of access ports proved useful for repeatedly aspirating oviductal fluid in vivo from cynomolgus monkeys that was free from artifactual contaminants and with no observable changes in the behavior or health of the animals. Subsequent assays of relative and absolute concentrations of antibodies in oviductal fluid and serum demonstrated the presence of IgA and IgG specific for the recombinant sperm immunogen SP-10 in fluid collected from the periovulatory oviduct of primates after intramuscular inoculations. The antibodies evoked by the recombinant sperm vaccinogen recognized the endogenous antigen target on both human and macaque sperm, lending support for the possibility of developing a contraceptive immunogen that prevents fertilization.

Acrosome↗

The serial organisation of behaviour by non-human primates; an evaluation of experimental paradigms.

On close examination of research programs which focus, either implicitly or explicitly, on the problem of the organisation of serial order in non-human primates, it is possible to detect some limitations in the paradigms conventionally used. Serial learning studies, which focus on the acquisition of arbitrary lists of unconnected elements point towards a distinction between the representation of ordered series formed by monkeys and pigeons. However, the use of unconnected items prevents an assay of the degree to which primates might be able to impose a structure over the list to be reported. The study of transitive reasoning has been implemented by means of a paradigm where the order of a series is conveyed be presenting a common item in pairs of binary discriminations. Animals tested with this paradigm develop control strategies using more information than that provided by reward contingencies alone. A restriction of this paradigm is that, in its binary form, it does not allow a differentiation between the performance of monkeys and pigeons and even simple models account for a transitive bias in the task. On the basis of these observations it is proposed that novel paradigms which go beyond the binary context, feature multiple connected items, and accord a high degree of spontaneity to the subjects might allow better than traditional ones to uncover qualitative different ways in which different organisms serially organise their behaviour. Some recent research programs based on such rationale, and implemented as search tasks, are then outlined and compared with other approaches to the study of search behaviour. Preliminary results obtained from these studies indicate that the spontaneous serial organisation of multiple connected items might uncover new dimensions of promising comparative relevance.

Animals↗

Evolution of MHC-G in humans and primates based on three new 3'UT polymorphisms.

MHC-G is a class Ib (non-classical) major histocompatibility complex (MHC) whose functional and evolutionary characteristics are still under scrutiny. The study of noncoding sequences in the MHC genes may provide important phylogenetic information. In this work we have sequenced the MHC-G exon 8, which encodes for the 3'UT region, in different species of primates. It has been shown that: (1) a previously described 14 base pair (bp) deletion polymorphism is human-specific and the HLA-G alleles may be classified according to its absence or presence; (2) another newly described 3 bp deletion/insertion polymorphism is also human-specific; and (3) another newly described 51 bp deletion polymorphism is common to Pongidae and humans, but is not found in other primates belonging to the Cercopithecinae family. A hypothesis on the evolutionary pathway of this gene is put forward in the light of these findings.

3' Untranslated Regions↗

Nonhuman primate models to evaluate vaccine safety and immunogenicity.

When considering preclinical studies to evaluate the safety and immunogenicity of putative vaccine candidates, such as nucleic acid vaccines, species most closely related to humans should be considered. Phylogenetically, the great apes (chimpanzees, orangutans, gorillas, and gibbons) are most closely related to humans. However, the great apes, which diverged from humans over 5 million years ago, represent endangered or threatened species that limits their utility in preclinical studies. In addition, cost considerations for using great apes in biomedical studies represents another serious limitation. The Old World monkeys, (macaques, baboons, mandrills, and mangabeys), diverged from humans over 15 million years ago. A number of the Old World monkey species including rhesus, cynomolgus, and African green monkeys, have also been employed in biomedical research to evaluate vaccine safety and immunogenicity. New World monkeys (aotus, owl, cebus monkeys, and marmosets) are the most phylogenetically divergent from humans, yet they have also been utilized to develop nonhuman primate models for a number of human infectious diseases and tumors. The advantages and disadvantages in selecting a particular nonhuman primate species for studies to evaluate DNA vaccine safety and immunogenicity are briefly discussed. Comparative immunology, reproductive physiology, endogenous infectious agents, and cost considerations are briefly described.

Animals↗

A comparative study on the cortico-hypoglossal connections in primates, using biotin dextranamine.

The anterograde projections of the motorcortical tongue area to the hypoglossal nucleus and neighbouring structures were studied in the rhesus monkey, squirrel monkey, saddle-back tamarin and tree shrew. Biotin dextranamine served as tracer. Direct projections into the hypoglossal nucleus were only found in the rhesus monkey and squirrel monkey. All four species, however, showed a direct projection into the dorsal and parvocellular reticular formation which in turn projects into the hypoglossal nucleus. The findings suggest a phylogenetic trend in the projections of the motorcortical tongue area from non-primate mammals via non-human primates to man in the sense that the cortico-motoneuronal connection is strengthened towards man. This might be one reason for the superior role the tongue plays in human vocal behaviour in contrast to non-human vocalization.

Animals↗

Variation of variable number of tandem repeat sequences in the 3'-untranslated region of primate dopamine transporter genes that affects reporter gene expression.

Genetic polymorphism has been reported in the 3'-untranslated region (3'-UTR) of the human dopamine transporter (DAT) gene and the variable number of tandem repeat (VNTR) polymorphism has been proposed to be associated with normal personal traits or psychoneurological disorders. To assess the variation of this region in nonhuman primates, we amplified the VNTR regions by the polymerase chain reaction in several species of apes and monkeys, and determined their DNA sequences. The 3'-UTR of the chimpanzee DAT gene was also polymorphic and alleles with one or two unit(s) of a 40 bp sequence were found, while all gorillas and orangutans examined had only 2-repeat allele. Cynomolgus macaques and African green monkeys shared 11- or 12-repeat and 5-repeat alleles, respectively. By performing transient transfection assay, we found that most of the VNTR sequences of nonhuman primates exhibited higher activities on reporter gene assay as compared to those of human 9-, 10- and 11-repeat sequences.

3' Untranslated Regions↗

Dynamics of regulatory evolution in primate beta-globin gene clusters: cis-mediated acquisition of simian gamma fetal expression patterns.

Phylogenetic reconstructions by parsimony were carried out on an enlarged body of primate gamma1 and gamma2-globin sequences. The results confirm that gamma1 and gamma2 arose from a tandem duplication in an ancient simian lineage ancestral to both platyrrhines (New World monkeys) and catarrhines (Old World monkeys and hominoids). Gene conversions between the two gamma homologs were frequent over the gamma gene proper but less frequent over the 5' flanking and very infrequent over the 3' flanking regions. The ancient platyrrhine conversion in the most distal 5' flanking region had the polarity of gamma2-->gamma1. Recent platyrrhine conversions between 5' regulatory sequences were very infrequent, in striking contrast to catarrhines which have large, uninterrupted stretches of converted 5' regulatory sequences. Comparisons of reconstructed ancestral primate and simian gamma promoter sequences revealed an accumulation of 21 nucleotide substitutions concentrated in or near cis-elements that may have mediated the change from embryonic to fetal gamma expression. Almost all 21 substitutions were retained in the lineages leading to functional gamma genes of extant catarrhines (both gamma1 and gamma2) and platyrrhines (most often gamma2). Fewer of these simian specific substitutions were retained in the platyrrhine gamma1 genes and new mutations occurred more often in the platyrrhine gamma1 than gamma2 promoters.

Animals↗

Use of primate folliculogenesis models in understanding human reproductive biology and applicability to toxicology.

The nonhuman primate reproductive system provides an excellent model for studying basic physiological processes applicable to humans. This article reviews hormonal observations and experimental manipulations useful in the evaluation of ovarian events in various stages of the reproductive life. As the need arises, primate reproductive toxicological studies may clarify questions relevant to human risk evaluations. Evaluation of reproductive toxicological observations may reveal biological parameters defining premature reproductive failure.

Animals↗

Nutritional characteristics of wild primate foods: do the diets of our closest living relatives have lessons for us?

The widespread prevalence of diet-related health problems, particularly in highly industrialized nations, suggests that many humans are not eating in a manner compatible with their biology. Anthropoids, including all great apes, take most of their diet from plants, and there is general consensus that humans come from a strongly herbivorous ancestry. Though gut proportions differ, overall gut anatomy and the pattern of digestive kinetics of extant apes and humans are very similar. Analysis of tropical forest leaves and fruits routinely consumed by wild primates shows that many of these foods are good sources of hexoses, cellulose, hemicellulose, pectic substances, vitamin C, minerals, essential fatty acids, and protein. In general, relative to body weight, the average wild monkey or ape appears to take in far higher levels of many essential nutrients each day than the average American and such nutrients (as well as other substances) are being consumed together in their natural chemical matrix. The recommendation that Americans consume more fresh fruits and vegetables in greater variety appears well supported by data on the diets of free-ranging monkeys and apes. Such data also suggest that greater attention to features of the diet and digestive physiology of non-human primates could direct attention to important areas for future research on features of human diet and health.

Animal Nutritional Physiological Phenomena↗

Comparative morphological studies on the stereo structure of the lingual papillae of selected primates using scanning electron microscopy.

A scanning electron microscope was used to observe the lingual papillae and their connective tissue cores (CTCs) in five primates (tupai, tamarin, crab-eating monkey, mandrill, and human). There were some slender protrusions rising from the top of the filiform papilla in all five types of primate. After removing the epithelium the filiform CTC from the tupai, tamarin and crab-eating monkey displayed a U-shaped arrangement of rod-shaped protrusions. The filiform CTC from the crab-eating monkey also had a columnar base. The human filiform CTC consisted of a primary columnar base, numerous short rod-shaped secondary protrusions from its upper periphery, and a few central protrusions. The filiform CTC from the Mandrill was fundamentally similar to that of the human, however, its base was shorter. The fungiform CTC from the tupai was column shaped, with several depressions for taste buds on the top. There were three vallate papillae in the tupai, tamarin, and mandrill, approximately four in the monkey, and between five and twelve in the human. Moderately developed foliate papillae were found in the tamarin, monkey, mandrill and human. The tupai, however, possessed a finger-like lateral organ instead. The lingual root area of the tupai, tamarin, crab-eating monkey and mandrill was relatively small with a smooth surface. Only the human had a tonsil-structure, which was located on the surface of its larger lingual root.

Animals↗

Influence of craniofacial morphology on primate paranasal pneumatization.

In order to test the hypothesis that variation in the maxillary sinus volume (MSV) of anthropoid primates is related to skull architecture, a mixed sex sample of adult primate crania covering Hominoidea, Cercopithecoidea and Ceboidea was examined using CT scans. MSV was regressed against basicranial length, using reduced major axis analysis. 2 distinct scaling patterns emerged: while a large MSV seems to be a primitive condition of Anthropoidea, it is clearly reduced in Cercopithecoidea. Although some correlations exist between MSV and different indices of the facial skeleton, they are relatively weak and differed among the 3 groups. A full appreciation of epigenetic factors and the relation of the paranasal sinuses to different cranial components is necessary to highlight the biological role of skull pneumatization.

Adult↗

The auditory behaviour of primates: a neuroethological perspective.

The ethological approach has already provided rich insights into the auditory neurobiology of a number of different taxa (e.g. birds, frogs and insects). Understanding the ethology of primates is likely to yield similar insights into the specializations of this taxa's auditory system for processing species-specific vocalisations. Here, we review the recent advances made in our understanding of primate vocal perception and its neural basis.

Animals↗

Colour coding in the primate retina: diverse cell types and cone-specific circuitry.

How is the trichromatic cone mosaic of Old World primates sampled by retinal circuits to create wavelength opponency? Red-green (L versus M cone) opponency appears to be mediated largely by the segregation of L versus M cone signals to the centre versus the surround of the midget ganglion cell receptive field, implying a complex cone type-specific wiring, the basis of which remains mysterious. Blue-yellow (S versus L+M cone) opponency is mediated by a growing family of low-density ganglion types that receive either excitatory or inhibitory input from S cones. Thus, the retinal circuits that underlie colour signalling in primates may be both more complex and more diverse then previously appreciated.

Animals↗

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