Hematologic and serum biochemical reference intervals for the chimpanzee (Pan troglodytes) categorized by age and sex

Normal reference range intervals for hematologic and serum biochemical values in the chimpanzee (Pan troglodytes) have seldom been reported. The few studies that have been conducted either report values on the basis of a small number of animals, report values for all age groups or both sexes combined, or were designed specifically to document the effect of a particular condition on the normal range of hematologic and serum biochemical values. On the basis of data collected from 133 chimpanzees over a 17-year period, empirically based clinical reference ranges were derived to provide a guide for basic diagnostic and clinical care of chimpanzees. For either sex within each of four age groups, there is a table that summarizes serum biochemical and a table that summarizes hematologic values. These values are compared with prior values, and their importance in the care and well being of captive chimpanzee populations is discussed.     

Normal hematologic and serum clinical chemistry values for captive chimpanzees (Pan troglodytes)

In the study reported here, reference intervals for hematologic and serum clinical chemistry variables in the chimpanzee (Pan troglodytes) were developed and characterized. Data were collected longitudinally across a 10-year period for 86 subjects at the Primate Foundation of Arizona (PFA). Variables included nine standard hematologic and 25 standard serum clinical chemistry values. An analysis of variance (ANOVA) was used to test for main effects by age and sex. In addition, PFA mean and range values were compared with those published for humans and six other chimpanzee colonies. The ANOVA results suggest an age effect on hematologic (mean corpuscular hemoglobin, mean corpuscular volume, neutrophils) and serum clinical chemical (creatinine, total protein, globulin, tryglycerides, direct bilirubin, iron, (gamma-glutamyltransferase, alanine transaminase, creatine kinase) values. In addition, sex had a main effect on several variables (red blood cells, hemoglobin concentration, hematocrit, uric acid and sodium concentrations, and aspartate transminase and creatine kinase activities); values for males were greater than those for females. Further, human and chimpanzee mean and range values often were indistinguishable from one another. However, changes in human and chimpanzee values associated with age differ and suggest that hematologic and serum clinical chemistry values may be differentially affected by physical and sexual maturation in humans and chimpanzees.     

Interaction sequences between chimpanzees and human visitors at the Zoo

Data were collected on the behavior and physical characteristics of 259 human visitors and 24 chimpanzees at Chester Zoo. The successive responses of humans and chimpanzees to each other's behavior were recorded, the resulting long sequence being referred to as an interaction sequence. There was no particular set of characteristics that distinguished interactors from noninteractors in either humans or chimpanzees, although there was some evidence that chimpanzees were particularly likely to respond to men carrying objects. Chimpanzee responses were random with respect to the previous human behavior, but human responses were significantly associated with the preceding chimpanzee behavior. In particular, chimpanzee sounds were likely to be followed by human sounds, and begging was likely to be followed by the offer of food. Interaction sequences varied in length, but 9% of chimpanzee-initiated sequences went as far as a ninth interaction. Sequences resulted in the chimpanzees being given food in 25% of human-initiated, but only 8% of chimpanzee-initiated sequences. The results are consistent with the interpretation that humans and chimpanzees are motivated to interact with one another and that the chimpanzees do this primarily to obtain food. © 1995 Wiley-Liss, Inc.     

Epidermal patterns of the hands and feet of the pygmy chimpanzee (Pan paniscus)

The characteristics of the epidermal ridge system were studied in a series of eighteen lesser or pygmy chimpanzees (Pan paniscus). The general ridge alignments are very similar to those of the chimpanzee (Pan troglodytes); Biegert ('61). On the average the pattern intensity (P.I.) of the palm configurations is considerably higher in the pygmy chimpanzee than in the chimpanzee, thus representing the highest total palm pattern intensity of all species of the Hominoidea. The sole configurations show parallel main results to those of the palm; however, the decreased sole pattern frequency of the pygmy chimpanzee is of a smaller predominance only as compared to the values of the other species of this superfamily. The preliminary data on the finger tip patterns, translated into P.I. values, are much higher than in chimpanzees and within the range of the mean values of gorillas (Brehme, '73), while those of the toes of pygmy chimpanzees seem to possess the lowest P.I. values of the African apes.     

How does stone-tool use emerge? Introduction of stones and nuts to naïve chimpanzees in captivity

Nut-cracking behavior has been reported in several communities in West Africa but not in East and Central Africa. Furthermore, even within nut-cracking communities, there are individuals who do not acquire the skill. The present study aimed to clarify the cognitive capability required for nut-cracking behavior and the process through which the the nut-cracking behavior emerges. To examine emergence, we provided three naïve adult chimpanzees with a single opportunity to observe human models. A human tester demonstrated nut-cracking behavior using a pair of stones and then supplied stones and nuts to the chimpanzee subjects. Two out of three chimpanzees proceeded to hit a nut on an anvil stone using a hammer stone, one of whom succeeded in cracking open the nuts during the first test session. The third chimpanzee failed to crack open nuts. We used four variables (object, location, body part used, and action) to describe stone/nut manipulation in order to analyze further the patterns of object manipulation exhibited by the subjects. The analysis revealed that there were three main difficulties associated with nut-cracking behavior. (1) The chimpanzee who failed at the task never showed hitting action. (2) The chimpanzee who failed at the task manipulated nuts but rarely stones. (3) The combination of three objects was not commonly observed in the three chimpanzees. We also discuss our results with reference to the effect of enculturation in captivity and the social context of learning in the wild.     

The evolutionary history of human and chimpanzee Y-chromosome gene loss

Recent studies have suggested that gene gain and loss may contribute significantly to the divergence between humans and chimpanzees. Initial comparisons of the human and chimpanzee Y-chromosomes indicate that chimpanzees have a disproportionate loss of Y-chromosome genes, which may have implications for the adaptive evolution of sex-specific as well as reproductive traits, especially because one of the genes lost in chimpanzees is critically involved in spermatogenesis in humans. Here we have characterized Y-chromosome sequences in gorilla, bonobo, and several chimpanzee subspecies for 7 chimpanzee gene-disruptive mutations. Our analyses show that 6 of these gene-disruptive mutations predate chimpanzee-bonobo divergence at approximately 1.8 MYA, which indicates significant Y-chromosome change in the chimpanzee lineage relatively early in the evolutionary divergence of humans and chimpanzees.     

Lessons from chimpanzee-based research on human disease: the implications of genetic differences

Assertions that the use of chimpanzees to investigate human diseases is valid scientifically are frequently based on a reported 98-99% genetic similarity between the species. Critical analyses of the relevance of chimpanzee studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for the chimpanzee to constitute a good model for research, and furthermore, that chimpanzee data do not translate well to progress in clinical practice for humans. Leading examples include the minimal citations of chimpanzee research that is relevant to human medicine, the highly different pathology of HIV/AIDS and hepatitis C virus infection in the two species, the lack of correlation in the efficacy of vaccines and treatments between chimpanzees and humans, and the fact that chimpanzees are not useful for research on human cancer. The major molecular differences underlying these inter-species phenotypic disparities have been revealed by comparative genomics and molecular biology - there are key differences in all aspects of gene expression and protein function, from chromosome and chromatin structure to post-translational modification. The collective effects of these differences are striking, extensive and widespread, and they show that the superficial similarity between human and chimpanzee genetic sequences is of little consequence for biomedical research. The extrapolation of biomedical data from the chimpanzee to the human is therefore highly unreliable, and the use of the chimpanzee must be considered of little value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to science.     

The quality of chimpanzee T-cell activation and simian immunodeficiency virus/human immunodeficiency virus susceptibility achieved via antibody-mediated T-cell receptor/CD3 stimulation is a function of the anti-CD3 antibody isotype

While human immunodeficiency virus type 1 (HIV-1) infection is associated with hyperimmune activation and systemic depletion of CD4⁺ T cells, simian immunodeficiency virus (SIV) infection in sooty mangabeys or chimpanzees does not exhibit these hallmarks. Control of immune activation is thought to be one of the major components that govern species-dependent differences in the disease pathogenesis. A previous study introduced the idea that the resistance of chimpanzees to SIVcpz infection-induced hyperimmune activation could be the result of the expression of select sialic acid-recognizing immunoglobulin (Ig)-like lectin (Siglec) superfamily members by chimpanzee T cells. Siglecs, which are absent on human T cells, were thought to control levels of T-cell activation in chimpanzees and were thus suggested as a cause for the pathogenic differences in the course of SIVcpz or HIV-1 infection. As in human models of T-cell activation, stimulation had been attempted using an anti-CD3 monoclonal antibody (MAb) (UCHT1; isotype IgG1), but despite efficient binding, UCHT1 failed to activate chimpanzee T cells, an activation block that could be partially overcome by MAb-induced Siglec-5 internalization. We herein demonstrate that anti-CD3 MAb-mediated chimpanzee T-cell activation is a function of the anti-CD3 MAb isotype and is not governed by Siglec expression. While IgG1 anti-CD3 MAbs fail to stimulate chimpanzee T cells, IgG2a anti-CD3 MAbs activate chimpanzee T cells in the absence of Siglec manipulations. Our results thus imply that prior to studying possible differences between human and chimpanzee T-cell activation, a relevant model of chimpanzee T cell activation needs to be established.     

Species differences in tears; Comparative investigation in the chimpanzee (Pan troglodytes)

This paper describes evolutionary divergence in composition of tear fluid among some mammals, and discusses the implications of these differences with regard to the choice of appropriate animals for use as models in ophthalmic research. For the first time a comprehensive investigation of tear fluid in the chimpanzee (Pan troglodytes) is presented in which tear fluid was collected during narcosis of eight chimpanzees. Total protein in chimpanzee tear fluid (8.8±0.3 g/l) is not significantly different from total protein of human tear fluid (10.0±0.6 g/l). The values in tear fluid for lysozyme (6.2±1.5 mg Hen Egg Lysozyme, HEL/ml), peroxidase (115±18 U/ml), and amylase (3.5±0.4 U/ml) in chimpanzees were significantly different from those of human lysozyme (11.8±1.6 mg HEL/ml), peroxidase (70±5 U/ml), and amylase (1.0±0.2 U/ml). Polyacrylamide gelelectrophoresis of tear fluid of the chimpanzees shows in comparison with human tear fluid an additional low-molecular protein (<14 kiloDalton).     

The resistance of HIV-infected chimpanzees to progression to AIDS correlates with absence of HIV-related T-cell dysfunction

Differences in the in vivo and in vitro responses of T lymphocytes from chimpanzees and human subjects were compared for evidence of HIV-1 related T-cell dysfunction. There was no increased level of programmed cell death (PCD) in HIV-1 infected chimpanzees in contrast to asymptomatic individuals. Anergy could be induced with HIV-1 gp120 in human but not chimpanzee T_H lymphocytes, however in vitro infection of chimpanzee T_H cultures with HIV-1 resulted in complete lysis of cells within three weeks. These findings suggest that the resistance of HIV-1 infected chimpanzees to progression to AIDS is due to their relative resistance to the systemic effects of HIV-1 on T-cell dysfunction.     

Reexamination of the African hominoid trichotomy with additional sequences from the primate beta-globin gene cluster.

Additional DNA sequence information from a range of primates, including 13.7 kb from pygmy chimpanzee (Pan paniscus), was added to data sets of beta-globin gene cluster sequence alignments that span the gamma 1, gamma 2, and psi eta loci and their flanking and intergenic regions. This enlarged body of data was used to address the issue of whether the ancestral separations of gorilla, chimpanzee, and human lineages resulted from only one trichotomous branching or from two dichotomous branching events. The degree of divergence, corrected for superimposed substitutions, seen in the beta-globin gene cluster between human alleles is about a third to a half that observed between two species of chimpanzee and about a fourth that between human and chimpanzee. The divergence either between chimpanzee and gorilla or between human and gorilla is slightly greater than that between human and chimpanzee, suggesting that the ancestral separations resulted from two closely spaced dichotomous branchings. Maximum parsimony analysis further strengthened the evidence that humans and chimpanzees share the longest common ancestry. Support for this human-chimpanzee clade is statistically significant at P = 0.002 over a human-gorilla clade or a chimpanzee-gorilla clade. An analysis of expected and observed homoplasy revealed that the number of sequence changes uniquely shared by human and chimpanzee lineages is too large to be attributed to homoplasy. Molecular clock calculations that accommodated lineage variations in rates of molecular evolution yielded hominoid branching times that ranged from 17-19 million years ago (MYA) for the separation of gibbon from the other hominoids to 5-7 MYA for the separation of chimpanzees from humans. Based on the relatively late dates and mounting corroborative evidence from unlinked nuclear genes and mitochondrial DNA for the close sister grouping of humans and chimpanzees, a cladistic classification would place all apes and humans in the same family. Within this family, gibbons would be placed in one subfamily and all other extant hominoids in another subfamily. The later subfamily would be divided into a tribe for orangutans and another tribe for gorillas, chimpanzees, and humans. Finally, gorillas would be placed in one subtribe with chimpanzees and humans in another, although this last division is not as strongly supported as the other divisions.     

Campylobacter troglodytis sp. nov., isolated from feces of human-habituated wild chimpanzees (Pan troglodytes schweinfurthii) in Tanzania

The transmission of simian immunodeficiency and Ebola viruses to humans in recent years has heightened awareness of the public health significance of zoonotic diseases of primate origin, particularly from chimpanzees. In this study, we analyzed 71 fecal samples collected from 2 different wild chimpanzee (Pan troglodytes) populations with different histories in relation to their proximity to humans. Campylobacter spp. were detected by culture in 19/56 (34%) group 1 (human habituated for research and tourism purposes at Mahale Mountains National Park) and 0/15 (0%) group 2 (not human habituated but propagated from an introduced population released from captivity over 30 years ago at Rubondo Island National Park) chimpanzees, respectively. Using 16S rRNA gene sequencing, all isolates were virtually identical (at most a single base difference), and the chimpanzee isolates were most closely related to Campylobacter helveticus and Campylobacter upsaliensis (94.7% and 95.9% similarity, respectively). Whole-cell protein profiling, amplified fragment length polymorphism analysis of genomic DNA, hsp60 sequence analysis, and determination of the mol% G+C content revealed two subgroups among the chimpanzee isolates. DNA-DNA hybridization experiments confirmed that both subgroups represented distinct genomic species. In the absence of differential biochemical characteristics and morphology and identical 16S rRNA gene sequences, we propose to classify all isolates into a single novel nomenspecies, Campylobacter troglodytis, with strain MIT 05-9149 as the type strain; strain MIT 05-9157 is suggested as the reference strain for the second C. troglodytis genomovar. Further studies are required to determine whether the organism is pathogenic to chimpanzees and whether this novel Campylobacter colonizes humans and causes enteric disease.     

A CD4 domain important for HIV-mediated syncytium formation lies outside the virus binding site

HIV infection of chimpanzees results in a chronic viremia unaccompanied by the ultimately fatal immunodeficiency that marks HIV infection in man. We show here that expression of HIV envelope proteins allows syncytium formation between cells expressing human but not chimpanzee or macaque CD4. We find that the CD4 sequences regulating cell fusion lie outside the recognized virus binding site; in the simplest exchange, chimpanzee CD4 bearing human residue 87 supports syncytium formation, while human CD4 bearing chimpanzee residue 87 does not. Neither the equilibrium nor the forward rate constants for HIV-CD4 association are affected by substitution at position 87. Infection of human cells expressing chimpanzee CD4 is insensitive to lysosomotropic agents, suggesting that viral penetration under these circumstances does not require endocytosis. The benign course of HIV infection in chimpanzees may reflect the failure of the host to support direct cell to cell transmission of the virus.     

Human and chimpanzee gene expression differences replicated in mice fed different diets

Although the human diet is markedly different from the diets of closely related primate species, the influence of diet on phenotypic and genetic differences between humans and other primates is unknown. In this study, we analyzed gene expression in laboratory mice fed diets typical of humans and of chimpanzees. The effects of human diets were found to be significantly different from that of a chimpanzee diet in the mouse liver, but not in the brain. Importantly, 10% of the genes that differ in their expression between humans and chimpanzee livers differed also between the livers of mice fed the human and chimpanzee diets. Furthermore, both the promoter sequences and the amino acid sequences of these diet-related genes carry more differences between humans and chimpanzees than random genes. Our results suggest that the mouse can be used to study at least some aspects of human-specific traits.     

Comparison of chimpanzee and human leukocyte Ig-like receptor genes reveals framework and rapidly evolving genes.

The leukocyte receptor complex (LRC) on human chromosome 19 contains related Ig superfamily killer cell Ig-like receptor (KIR) and leukocyte Ig-like receptor (LIR) genes. Previously, we discovered much difference in the KIR genes between humans and chimpanzees, primate species estimated to have approximately 98.8% genomic sequence similarity. Here, the common chimpanzee LIR genes are identified, characterized, and compared with their human counterparts. From screening a chimpanzee splenocyte cDNA library, clones corresponding to nine different chimpanzee LIRs were isolated and sequenced. Analysis of genomic DNA from 48 unrelated chimpanzees showed 42 to have all nine LIR genes, and six animals to lack just one of the genes. In structural diversity and functional type, the chimpanzee LIRs cover the range of human LIRs. Although both species have the same number of inhibitory LIRs, humans have more activating receptors, a trend also seen for KIRs. Four chimpanzee LIRs are clearly orthologs of human LIRs. Five other chimpanzee LIRs have paralogous relationships with clusters of human LIRs and have undergone much recombination. Like the human genes, chimpanzee LIR genes appear to be organized into two duplicated blocks, each block containing two orthologous genes. This organization provides a conserved framework within which there are clusters of faster evolving genes. Human and chimpanzee KIR genes have an analogous arrangement. Whereas both KIR and LIR genes can exhibit greater interspecies differences than the genome average, within each species the LIR gene family is more conserved than the KIR gene family.     

Analysis of chimpanzee history based on genome sequence alignments

Population geneticists often study small numbers of carefully chosen loci, but it has become possible to obtain orders of magnitude for more data from overlaps of genome sequences. Here, we generate tens of millions of base pairs of multiple sequence alignments from combinations of three western chimpanzees, three central chimpanzees, an eastern chimpanzee, a bonobo, a human, an orangutan, and a macaque. Analysis provides a more precise understanding of demographic history than was previously available. We show that bonobos and common chimpanzees were separated ~1,290,000 years ago, western and other common chimpanzees ~510,000 years ago, and eastern and central chimpanzees at least 50,000 years ago. We infer that the central chimpanzee population size increased by at least a factor of 4 since its separation from western chimpanzees, while the western chimpanzee effective population size decreased. Surprisingly, in about one percent of the genome, the genetic relationships between humans, chimpanzees, and bonobos appear to be different from the species relationships. We used PCR-based resequencing to confirm 11 regions where chimpanzees and bonobos are not most closely related. Study of such loci should provide information about the period of time 5–7 million years ago when the ancestors of humans separated from those of the chimpanzees.     

Auditory ERPs to stimulus deviance in an awake chimpanzee (Pan troglodytes): towards hominid cognitive neurosciences

Background

For decades, the chimpanzee, phylogenetically closest to humans, has been analyzed intensively in comparative cognitive studies. Other than the accumulation of behavioral data, the neural basis for cognitive processing in the chimpanzee remains to be clarified. To increase our knowledge on the evolutionary and neural basis of human cognition, comparative neurophysiological studies exploring endogenous neural activities in the awake state are needed. However, to date, such studies have rarely been reported in non-human hominid species, due to the practical difficulties in conducting non-invasive measurements on awake individuals.

Methodology/Principal Findings

We measured auditory event-related potentials (ERPs) of a fully awake chimpanzee, with reference to a well-documented component of human studies, namely mismatch negativity (MMN). In response to infrequent, deviant tones that were delivered in a uniform sound stream, a comparable ERP component could be detected as negative deflections in early latencies.

Conclusions/Significance

The present study reports the MMN-like component in a chimpanzee for the first time. In human studies, various ERP components, including MMN, are well-documented indicators of cognitive and neural processing. The results of the present study validate the use of non-invasive ERP measurements for studies on cognitive and neural processing in chimpanzees, and open the way for future studies comparing endogenous neural activities between humans and chimpanzees. This signifies an essential step in hominid cognitive neurosciences.     

Chimpanzees (<Emphasis Type="Italic">Pan troglodytes</Emphasis>) learn to act with other individuals in a cooperative task

We presented two chimpanzees with a task in which they were required to pull each end of a rope simultaneously to drag blocks supporting food into reach. The chimpanzees did not succeed in initial tests. They did not immediately understand the necessity for cooperation, and they did not adjust their behavior to work with the partner. However, the frequency of success gradually increased as the number of sessions increased and the task was varied. They began to look at the partner frequently, wait if the partner was not holding the rope, and pull the rope in synchrony with the partner. However, they did not use interactive behaviors or eye contact to synchronize their behavior. One chimpanzee was then paired with a human partner in the same situation. After initial failures, the chimpanzee began to solicit the human partner for cooperation: looking up at his face, vocalizing, and taking the partner’s hand. When this chimpanzee was again paired with the chimpanzee partner, no soliciting behavior was observed. Thus, the chimpanzees could learn to coordinate their behavior through trial and error. Communicative behavior emerged during the task, but the communication differed according to the identity of the partner.     

A chimpanzee-passaged human immunodeficiency virus isolate is cytopathic for chimpanzee cells but does not induce disease.

The human immunodeficiency virus type 1 (HIV-1) readily infects both humans and chimpanzees, but the pathologic outcomes of infection in these two species differ greatly. In attempts to identify virus-cell interactions that might account for this differential pathogenicity, chimpanzee peripheral blood lymphocytes and bone marrow macrophages were assessed in vitro for their ability to support the replication of several HIV-1 isolates. Although the IIIb, RF, and MN isolates did not readily infect chimpanzee peripheral blood lymphocytes, an isolate of HIV-1 passaged in vivo in chimpanzees not only replicated well in both chimpanzee peripheral blood lymphocytes and bone marrow macrophages but also was cytopathic for chimpanzee CD4+ lymphocytes. Because no evidence of HIV-induced disease has been observed in chimpanzees infected with this isolate, in vitro replication to high titers with concomitant loss of CD4+ cells is not, in this instance, a correlate of pathogenicity. These observations, therefore, indicate that caution must be used when making extrapolations from in vitro data to in vivo pathogenesis.     

Fatal Chimpanzee Attack in Loango National Park,Gabon

In some populations, chimpanzees engage in lethal aggression within and between social units. We report a fatal attack on an adult male chimpanzee at a new research site in Loango National Park, Gabon. We found a fresh corpse of an adult male chimpanzee only a few hundred meters from the research camp, after noting numerous vocalizations and chimpanzee movements the previous evening. Previous contacts with chimpanzees and fresh tracks in the area around the corpse suggest that 2 communities of chimpanzees range where the attack occurred and that members of the neighboring community killed the chimpanzee. To support the conclusion, we conducted genetic analysis for 13 Y-chromosome loci and 9 microsatellite loci of fecal samples from the dead individual, 5 possible attackers, and 2 members of the other community Though we cannot exclude the possibility of an intracommunity killing, the combined observational and genetic evidence suggest an intercommunity attack. The case study adds to the growing evidence that intercommunity killings are a rare but widespread phenomenon among chimpanzees and not an artifact of human provisioning or habituation.