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Posttransplant lymphoproliferative disorder associated with primate gamma-herpesvirus in cynomolgus monkeys used in pig-to-primate renal xenotransplantation and primate renal allotransplantation.

BACKGROUND: A series of immunosuppressed cynomolgus monkeys were used in porcine-to-primate and primate-to-primate renal transplantation. In a number of animals nodal and extranodal lymphomas as well as areas of lymphoid hyperplasia in multiple organs (posttransplant lymphoproliferative disorder, PTLD) were recorded. METHODS: PTLD was characterized with respect to manifestation sites, histopathology, immunophenotype, and association with primate Epstein Barr-like Virus by in situ hybridization and quantitative polymerase chain reaction. RESULTS: PTLD was observed in 10 of 245 xenotransplanted and 9 of 231 allotransplanted monkeys; its detection in xenotransplanted animals was significantly earlier after transplantation than that in allo-transplanted animals (median, 40 and 104 days, respectively; P<0.001). In the xenotransplanted animals, four cases showed a B-cell lymphoma and six cases were nonneoplastic (lymphoid hyperplasia). All nine PTLD cases from allotransplanted animals were diagnosed as lymphoma. There was no clear relationship between the use of a particular drug or drug combination in maintenance immunosuppression and the occurrence of PTLD. Fourteen of 19 animals (six of the cases from xenotransplants, eight from the allotransplant series) were positive by in situ hybridization with oligonucleotide probes detecting primate gamma-herpesvirus. CONCLUSION: These data indicate that PTLD in the xeno- and allotransplanted cynomolgus monkeys are associated with primate gamma-herpesvirus-induced B-cell proliferation.

Animals↗

Micronucleated erythrocyte frequencies in old and new world primates: measurement of micronucleated erythrocyte frequencies in peripheral blood of Callithrix jacchus as a model for evaluating genotoxicity in primates.

Nonhuman primates are of particular relevance in evaluating the potential toxicity of drugs and environmental agents. We have used previously published information and data from the present study to establish a relationship for New World (NW) and Old World (OW) primates on the basis of the frequency of spontaneous micronucleated erythrocytes (MNEs) observed in peripheral blood. Data on spontaneous MNEs in peripheral blood from 15 species of primates, including humans, indicate that NW primates have significantly (P < 0.01) higher MNE frequencies (group mean, 9.5 +/- 7.3 MNEs/10,000 erythrocytes; range, 0.7-20.5/10,000 erythrocytes) than OW primates (group mean, 1.0 +/- 0.9 MNEs/10,000 erythrocytes; range, 0.0-2.6 MNEs/10,000 erythrocytes). Humans are believed to have developed in the OW, and human MNE frequencies were similar to those described for OW primate species. We selected the common marmoset (Callithrix jacchus), a NW primate, to determine whether therapeutic pediatric doses of Metotrexate (MTX; 2.5 mg/kg), Cyclophosphamide (CP; 5 mg/kg), Cytosine-arabinoside (Ara-C; 3 mg/kg), or 5-Fluorouracil (5-FU; 10 mg/kg), administered daily for two consecutive days, increase the frequency of micronuclei. Micronucleated polychromatic erythrocyte frequencies were increased significantly in groups receiving MTX, CP and Ara-C, while MNE frequencies were increased by the Ara-C treatment. The results of this study indicate that NW primates have higher spontaneous MNE frequencies than OW primates, and because of this, NW primates like the common marmoset, may be suitable for evaluating the genotoxicity of chemical agents.

Animals↗

Compliant walking in primates: elbow and knee yield in primates compared to other mammals.

It has been suggested that primates utilize a compliant gait to help reduce peak locomotor stresses on their limbs (Schmitt [1994] J. Hum. Evol. 26:441-458; Schmitt [ 1998] Primate Locomotion, p. 175-200; Schmitt [ 1999] J. Zool. Lond. 248:149-160). However, the components of such a gait, i.e., increased step length, prolonged contact time, and substantial limb yield, have only been documented on a handful of primate species. In order to explore the generality of this claim, elbow and knee angles during walking were documented at touchdown, midstance, and liftoff in a sample of primates, carnivores, marsupials, rodents, and artiodactyls, all under 25 kg. Limb yield was calculated as the change in angle from touchdown to midstance, and re-extension as the change in angle from midstance to liftoff for both forelimbs and hind limbs. Use of a compliant gait (as reflected in significant limb yield) in primates was confirmed for both forelimbs and hind limbs. However, there was variability within primates in the degree of either elbow or knee yield. Surprisingly, marsupials were found to exhibit almost as much elbow yield and even greater knee yield than primates. Carnivores and rodents display a modest amount of limb yield during walking, while artiodactyls appear to display a relatively stiff gait. These data are consistent with the suggestion that the use of a compliant gait to attenuate peak substrate reaction forces may have facilitated the primate invasion of a small-branch niche. However, limb compliance (as reflected by elbow or knee yield) does not appear to be exclusive to the primate order.

Animals↗

A comparison of primate, carnivoran and rodent limb bone cross-sectional properties: are primates really unique?

The cross-sectional properties of mammalian limb bones provide an important source of information about their loading history and locomotor adaptations. It has been suggested, for instance, that the cross-sectional strength of primate limb bones differs from that of other mammals as a consequence of living in a complex arboreal environment (Kimura, 1991, 1995). In order to test this hypothesis more rigorously, we have investigated cross-sectional properties in samples of humeri and femora of 71 primate species, 30 carnivorans and 59 rodents. Primates differ from carnivorans and rodents in having limb bones with greater cross-sectional strength than mammals of similar mass. This might imply that primates have stronger bones than carnivorans and rodents. However, primates also have longer proximal limb bones than other mammals. When cross-sectional dimensions are regressed against bone length, primates appear to have more gracile bones than other mammals. These two seemingly contradictory findings can be reconciled by recognizing that most limb bones experience bending as a predominant loading regime. After regressing cross-sectional strength against the product of body mass and bone length, a product which should be proportional to the bending moments applied to the limb, primates are found to overlap considerably with carnivorans and rodents. Consequently, primate humeri and femora are similar to those of nonprimates in their resistance to bending. Comparisons between arboreal and terrestrial species within the orders show that the bones of arboreal carnivorans have greater cross-sectional properties than those of terrestrial carnivorans, thus supporting Kimura's general notion. However, no differences were found between arboreal and terrestrial rodents. Among primates, the only significant difference was in humeral bending rigidity, which is higher in the terrestrial species. In summary, arboreal and terrestrial species do not show consistent differences in long bone reinforcement, and Kimura's conclusions must be modified to take into account the interaction of bone length and cross-sectional geometry.

Animals↗

Human anti-heparin-platelet factor 4 antibodies are capable of activating primate platelets: towards the development of a HIT model in primates.

In the first step to establish an animal model of heparin-induced thrombocytopenia (HIT) that is physiologically relevant to humans, studies were undertaken to determine the similarities or differences between human and non-human primate (Macaca mulatta) platelets in HIT assay systems. The collagen-, ADP-, and TRAP-induced platelet aggregation, and flow cytometric analysis of P-selectin expression and microparticle formation were similar for both species platelets (p>0.1, n=18 each). The classical HIT assays using platelet-rich plasma (PRP) as well as a flow cytometric assay revealed the activation/aggregation and serotonin release assay (SRA) profiles for both primate and human platelets were similar in response to human HIT positive sera. All assays were heparin concentration-dependent; heparin, at 0.1 U/mL, produced maximum and similar platelet activation/aggregation and SRA responses with both primate (76+/-7%, n=18) and human (68+/-11%, n=20; p>0.1) platelets. At concentrations > or =10 U/mL, heparin suppressed the platelet aggregation and SRA responses in both systems. Primate and human platelets displayed similar behavior to low molecular weight heparin and pentasaccahride in HIT assay systems. Immunoglobulins isolated from serum of patients with HIT caused activation/aggregation of human (65+/-18%, n=10 donors) and primate (79+/-12%, n=6 monkeys, p>0.08) platelets. Unlike human platelets, the primate platelets exhibited a more consistent aggregation/release response (15 out of 18 primate platelets reactive). In contrast, human donors showed wide variations in the activation/release response (4 out of 10 reactive). These observations suggest that primate platelets are activatable by anti-H-PF4 antibodies, and support the hypothesis that primates can be used to develop an animal model to study the pathogenesis of HIT.

Animals↗

New Palaeogene primate basicrania and the definition of the order Primates.

The anatomy of the posterior basicranium has been repeatedly invoked in systematic definitions of Primates. One widely cited definition of the order claims that 'all undoubted primates' are distinguished from other mammals by two basicranial specializations: (1) absence of a major vascular foramen on the medial side of the auditory region, and (2) development of the auditory bulla from the petrosal bone. As we show here, specialization (1) does not apply to the paromomyid Ignacius, and is of uncertain incidence in other unquestioned members of suborder Plesiadapiformes (archaic primates from the early Cenozoic of Europe and North America). Specialization (2) cannot be demonstrated without ontogenetic evidence, and all relevant plesiadapiform fossils are adult. In fact, the only plesiadapiform with an arterial pattern remotely resembling that of early primates of modern aspect (or 'euprimates') is the microsyopid Cynodontomys, but it is often regarded as non-primate because it lacks a petrosal bulla. Although plesiadapiforms resemble euprimates in traits of the cheek teeth and postcranium, some other (presumably non-primate) groups possess these traits as well. Since the order Primates is not clearly definable by unique specializations, the best grounds for regarding plesiadapiforms as euprimate antecedents are stratigraphic and phenetic. This fact may be best expressed by systematic arrangements that emphasize adaptive grades rather than unsubstantiated clades.

Animals↗

Evolution of the sweetness receptor in primates. II. Gustatory responses of non-human primates to nine compounds known to be sweet in man.

The gustatory responses of nine compounds, namely glycine, D-phenylalanine, D-tryptophan, cyanosuosan, magapame, sucrononate, campame, cyclamate and superaspartame, all known as sweet in man, were studied in 41 species or subspecies of non-human primates, selected among Prosimii (Lemuridae and Lorisidae), Platyrrhini (Callitrichidae and Cebidae) and Catarrhini (Cercopithecidae, Hylobatidae and Pongidae). The first six compounds are generally sweet to all primates, which implies that they interact with the primate sweetness receptors essentially through constant recognition sites. Campame is sweet only to Cebidae and Catarrhini, cyclamate only to Catarrhini, superaspartame principally to Callitrichidae and Catarrhini, which implies that all these compounds interact with the receptors partly through variable recognition sites. From the present work, from other previous results (where notably it was observed that alitame is sweet to all primates, ampame only to Prosimii and Catarrhini, and aspartame only to Catarrhini), and from the multipoint attachment (MPA) theory of sweetness reception (as elaborated by Nofre and Tinti from a detailed study of structure-activity relationships of various sweeteners in man), it is inferred that the primate sweetness receptors are very likely made up of eight recognition sites, of which the first, second, third, fourth, seventh and eighth are constant, and the fifth and sixth variable. From these results and from the MPA theory, it is also inferred that the recognition sites of the primate sweetness receptors could be: Asp-1 or Glu-1, Lys-2, Asp-3 or Glu-3, Thr-4, X-5, X-6, Thr-7, Ser-8, where the variable recognition sites X-5 and X-6 would be: Ala-5 and Ala-6 for Callitrichidae, Ser-5 and Ala-6 for Cebidae, Ala-5 and Thr-6 for Prosimii, and Thr-5 and Thr-6 for Catarrhini. By using Tupaiidae (tree shrews) as a reference outgroup and by means of other structural and functional molecular considerations, it appears that Callitrichidae have retained the most primitive receptor among the four types of primate receptors. The possible taxonomic and phylogenetic implications of these findings are discussed.

Animals↗

Complement receptor expression of primates and non-primates detected by the rosette formation technique.

The expression of complement receptors were studied on erythrocytes and platelets from 14 non-human primates and 3 non-primate species by rosette formation. It was found that the reactivity of erythrocytes with the cell bound complement is deeply dependent on which species are used as the complement source. The erythrocytes from Prosimian do not react with any kind of complement, while their platelets react with many kinds of complement. New World monkey erythrocytes do not react with indicator cells binding complements from guinea pig or man, while some of them react with indicators binding complements from non-human primate species. Contrarily Old World monkey erythrocytes react with complements from guinea pig, man and non-human primate. Hominoidea erythrocytes reacted with all the complements tested. Rabbit expresses C3 receptors on their erythrocytes for rabbit C3 and on their platelets for rabbit, guinea pig or mouse C3. Guinea pig expresses receptors on their erythrocytes for guinea pig and mouse C3, and on their platelets for guinea pig, mouse, rabbit and human C3. It becomes clear that not all of erythrocytes from primate and platelets from non-primate always express complement receptors as has been stated in the text books.

Animals↗

The olfactory receptor gene repertoire in primates and mouse: evidence for reduction of the functional fraction in primates.

Olfactory receptors (ORs) located in the cell membrane of olfactory sensory neurons of the nasal epithelium are responsible for odor detection by binding specific odorant ligands. Primates are thought to have a reduced sense of smell (microsmatic) with respect to other mammals such as dogs or rodents. We have previously demonstrated that over 70% of the human OR genes have become nonfunctional pseudogenes, leading us to hypothesize that the reduced sense of smell could correlate with the loss of functional genes. To extend these results, we sampled the OR gene repertoire of 10 primate species, from prosimian lemur to human, in addition to mouse. About 221 previously unidentified primate sequences and 33 mouse sequences were analyzed. These sequences encode ORs distributed in seven families and 56 subfamilies. Analysis showed a high fraction ( approximately 50% on average) of pseudogenes in hominoids. In contrast, only approximately 27% of OR genes are pseudogenes in Old World monkeys, and New World monkeys are almost free of pseudogenes. The prosimian branch seems to have evolved differently from the other primates and has approximately 37% pseudogene content. No pseudogenes were found in mouse. With the exception of New World monkeys, we demonstrate that primates have a high fraction of OR pseudogenes compared with mouse. We hypothesize that under relaxed selective constraints, primates would have progressively accumulated pseudogenes with the highest level seen in hominoids. The fraction of pseudogenes in the OR gene repertoire could parallel the evolution of the olfactory sensory function.

Animals↗

Mediolateral reaction forces and forelimb anatomy in quadrupedal primates: implications for interpreting locomotor behavior in fossil primates.

The forelimb joints of terrestrial primate quadrupeds appear better able to resist mediolateral (ML) shear forces than those of arboreal quadrupedal monkeys. These differences in forelimb morphology have been used extensively to infer locomotor behavior in extinct primate quadrupeds. However, the nature of ML substrate reaction forces (SRF) during arboreal and terrestrial quadrupedalism in primates is not known. This study documents ML-SRF magnitude and orientation and forelimb joint angles in six quadrupedal anthropoid species walking across a force platform attached to terrestrial (wooden runway) and arboreal supports (raised horizontal poles). On the ground all subjects applied a lateral force in more than 50% of the steps collected. On horizontal poles, in contrast, all subjects applied a medially directed force to the substrate in more than 75% of the steps collected. In addition, all subjects on arboreal supports combined a lower magnitude peak ML-SRF with a change in the timing of the ML-SRF peak force. As a result, during quadrupedalism on the poles the overall SRF resultant was relatively lower than it was on the runway. Most subjects in this study adduct their humerus while on the poles. The kinetic and kinematic variables combine to minimize the tendency to collapse or translate forelimbs joints in an ML plane in primarily arboreal quadrupedal primates compared to primarily terrestrial quadrupedal ones. These data allow for a more complete understanding of the anatomy of the forelimb in terrestrial vs. arboreal quadrupedal primates. A better understanding of the mechanical basis of morphological differences allows greater confidence in inferences concerning the locomotion of extinct primate quadrupeds.

Animals↗

Social interaction in nonhuman primates: an underlying theme for primate research.

Social living is assumed to be a critical feature of nonhuman primate existence inasmuch as most primate species live in social groups in nature. Recent USDA legislation emphasizes the importance of social contact in promoting psychological well-being and recommends that laboratory primates be housed with companions when consistent with research protocols. Our goals were to examine the link between social housing and psychological well-being and to explore the idea that research may be compromised when primates are studied in environments that vary too greatly from their natural ecological setting (individual cage housing versus group housing). Three general points emerge from these examinations. First, providing companionship may be a very potent way in which to promote psychological well-being in nonhuman primates; however, social living is not synonymous with well-being. The extent to which social housing promotes psychological well-being can vary across species and among individual members of the same species (for example, high- and low-ranking monkeys). Secondly, housing conditions can affect research outcomes in that group-housed animals may differ from individually housed animals in response to some manipulation. Social interaction may be a significant variable in regulating the biobehavioral responses of nonhuman primates to experimental manipulations. Finally, a larger number of socially housed subjects than individually housed subjects may be necessary for some biomedical research projects to yield adequate data analysis. Thus, social living has significant benefits and some potential costs not only for the animals themselves, but for the research enterprise.

Animals↗

Accidental injuries associated with nonhuman primate exposure at two regional primate research centers (USA): 1988-1993.

Although occupationally acquired zoonoses of nonhuman primates have been well documented, the epidemiology of work-related injuries associated with occupational exposure to nonhuman primates has not been studied. To investigate such injuries, we retrospectively reviewed injury records at one regional primate research center and distributed a self-administered, anonymous questionnaire to at-risk personnel at two centers. Records of bite, animal-inflicted scratch, needlestick, cut, and mucous membrane exposure injuries were reviewed at one center for the 5-year period 1988 to 1993 to determine incidence and frequency of injuries and to identify possible risk factors. A total of 261 injuries were reported during this period, with an annual incidence for all injuries combined ranging from 43.5 to 65.5 injuries per 100,000 person workdays (pwd) at risk. For specific injuries the highest incidence was observed for animal-inflicted scratches and bites, with a rate of 82 and 81 per 100,000 pwd respectively. The job category Veterinary Resident was found to have the highest incidence for needlestick injuries (547 per 100,000 pwd), scratches (239 per 100,000 pwd), and cuts (171 per 100,000 pwd). The highest rates for bites were observed in the job categories Animal Health Technician and Animal Technician, with 171 and 150 per 100,000 pwd respectively; the category Staff Veterinarian had the highest rate of mucous membrane exposures (71 per 100,000 pwd). The frequency of all injuries was greatest in personnel employed < or = 2 years. Questionnaire responses indicated that having > 20 h per week of contact with nonhuman primates or contact with more than 50 nonhuman primates per week was associated with a significantly increased risk of bites, animal-inflicted scratches, needlesticks, and mucous membrane exposures. In addition, data analysis indicated that under-reporting of work-related injuries was high; 59% of scratches, 50% of mucous membrane exposures, 45% of cuts, 37% of bites, and 20% of needlestick injuries went unreported. Results of this study identify job categories with a high incidence of specific injuries, for which additional targeted training and prevention programs may be beneficial, as well as providing quantitative baseline data for evaluating the effectiveness of any new safety programs or practices.

Accidents, Occupational↗

Primate photopigments and primate color vision.

The past 15 years have brought much progress in our understanding of several basic features of primate color vision. There has been particular success in cataloging the spectral properties of the cone photopigments found in retinas of a number of primate species and in elucidating the relationship between cone opsin genes and their photopigment products. Direct studies of color vision show that there are several modal patterns of color vision among groupings of primates: (i) Old World monkeys, apes, and humans all enjoy trichromatic color vision, although the former two groups do not seem prone to the polymorphic variations in color vision that are characteristic of people; (ii) most species of New World monkeys are highly polymorphic, with individual animals having any of several types of dichromatic or trichromatic color vision; (iii) less is known about color vision in prosimians, but evidence suggests that at least some diurnal species have dichromatic color vision; and (iv) some nocturnal primates may lack color vision completely. In many cases the photopigments and photopigment gene arrangements underlying these patterns have been revealed and, as a result, hints are emerging about the evolution of color vision among the primates.

Animals↗

The primate embryo gene expression resource: a novel resource to facilitate rapid analysis of gene expression patterns in non-human primate oocytes and preimplantation stage embryos.

Detailed molecular studies of preimplantation stage development in a suitable nonhuman primate model organism have been inhibited due to the cost and scarcity of embryos. To circumvent these limitations, we have created a new resource for the research community, designated as the Primate Embryo Gene Expression Resource (PREGER). The PREGER sample collection currently contains over 160 informative samples of oocytes, obtained from various sized antral follicles, and embryos obtained through a variety of different protocols. The PREGER makes it possible to undertake quantitative gene-expression studies in rhesus monkey oocytes and embryos through simple and cost-effective hybridization-based methods. The PREGER also makes available other molecular tools to facilitate nonhuman primate embryology. We used PREGER here to compare the temporal expression patterns of five housekeeping mRNAs and three transcription factor mRNAs between mouse and rhesus monkey. We observed noticeable differences in temporal expression patterns between species for some mRNAs, but clear similarities for others. Our results also provide new information related to genome activation and the effects of embryo culture conditions on gene expression in primate embryos. These results provide one illustration of how the PREGER can be employed to obtain novel insight into primate embryogenesis.

Animals↗

The MPTP-treated primate as a model of motor complications in PD: primate model of motor complications.

Motor complications are a common cause of treatment failure in Parkinson's disease (PD). Although the underlying mechanisms remain obscure, research with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates may facilitate their investigation. Repeated administration of L-dopa to MPTP-treated primates results in a loss of drug efficacy ("wearing off") and periods of immobility ("on-off"). Immediately after each dose of L-dopa, animals show an initial worsening of motor performance ("beginning-of-dose deterioration") and, at the end of action of each dose, they exhibit a decline to levels of disability below those seen at baseline ("rebound worsening"). Dyskinesia (chorea, dystonia, athetosis) appears rapidly in MPTP-treated primates given L-dopa. The greater the degree of nigral denervation, the less exposure to L-dopa that is required to induce dyskinesia. The onset and intensity of dyskinesia are related to the dose and frequency of L-dopa administration. Increasing brain exposure to L-dopa increases the severity and intensity of involuntary movements. In contrast, long-acting dopamine agonists (DAs) induce a far lower incidence of dyskinesia, and continuous dopaminergic stimulation may provide a means of avoiding its onset. Recent data from MPTP-treated primates suggest that switching from L-dopa to a long-acting DA may reverse the priming process associated with induction of dyskinesia. Responses of MPTP-treated primates have proved to be highly predictive of antiparkinsonian activities of drugs in humans and their ability to induce dyskinesia, but they may also have utility in evaluating the mechanisms that underlie a range of long-term motor complications affecting patients with PD.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Myelo- and cytoarchitecture of the granular frontal cortex and surrounding regions in the strepsirhine primate Galago and the anthropoid primate Macaca.

As the first part of a comparative investigation of primate frontal cortex, we compared the frontal architectonic organization of Galago, a small-brained, strepsirhine (or "prosimian") primate, to that of an anthropoid primate, Macaca, by using myelin- and Nissl-stained material. We were able to distinguish many more areas in both taxa than have been recognized in most previous studies of the primate frontal lobe. In particular, we were able to subdivide many of the areas shown in the commonly cited architectonic map of Walker (J. Comp. Neurol. 73:59-86, 1940). Delineation of areas was greatly facilitated by the use of the Gallyas technique for staining myelin. The areal organization of much of frontal cortex (specifically, the premotor, orbital, and medial regions) appears to be very similar in Galago and Macaca. In these regions, we were able to recognize the same complement of areas in both taxa, with few exceptions. In the granular frontal cortex (GFC), by contrast, we were able to distinguish about twice as many areas in Macaca as in Galago. For most of the GFC areas of Galago, there are architectonically similar areas in Macaca; the areas shared by both taxa correspond mainly to the arcuate and superior areas of Macaca (i.e., the region encompassed by Walker's areas 45, 8A, and 8B). However, there are many additional, more rostral, areas in Macaca for which there are no obvious homologues in Galago. In particular, Galago lacks cortex resembling the distinctive, lightly myelinated cortex of the Macaca principal sulcus (Walker's area 46 and its subdivisions). Our results are difficult to reconcile with the view that frontal lobe organization varies little across taxa. Rather, they suggest that granular frontal cortex underwent considerable change during primate evolution, including the addition of new areas in anthropoids.

Animals↗

The effects of caretaker-primate relationships on primates in the laboratory.

As contact with caretakers is likely to make up the majority of human-primate interactions in laboratories, caretakers represent an important influence in the lives of captive primates. The aim of this study was to determine how caretaker-primate relationships affected the behavior of primates in the laboratory. We examined whether stump-tailed macaques (Macaca arctoides) who were evaluated by caretakers as being either friendly or unfriendly differed in the quality and quantity of interactions with their caretakers during husbandry procedures and in their behavior at times of high and low levels of caretaker activity. Results revealed that animals who had friendly relationships with caretakers were less disturbed by routine husbandry procedures, approached caretakers more often, and were willing to accept food offered by caretakers compared with animals considered unfriendly toward their caretakers. The study concluded that the quality of the primate-caretaker relationship may have an important impact on behavior and may have implications for the well-being of animals and caretakers, as both can benefit from positive feedback from one another.

Animal Welfare↗