Primate Biology最新文献

This study was undertaken to investigate the susceptibility of rhesus monkeys to the calpox virus, an orthopoxvirus (OPXV) of the Cowpox virus species (CPXV), which is uniformly lethal in common marmosets. Six rhesus monkeys were either intravenously (i.v.) or intranasally (i.n.) exposed to the virus. Monitoring of the macaques after viral exposure included physical examinations, the determination of viral load by real-time PCR and plaque assay, and the analysis of humoral responses. Two i.v. inoculated animals developed numerous classical pox lesions that started after inoculation at days 7 and 10. Both animals became viremic and seroconverted. They exhibited maximal numbers of lesions of approximately 50 and 140 by day 21. One animal completely recovered, while the other one suffered from a phlegmonous inflammation of a leg initially induced by a secondarily infected pox lesion and was euthanized for animal welfare reasons. In contrast to previous pathogenicity studies with the calpox virus in marmosets, none of the four animals inoculated intranasally with doses of the calpox virus exceeding those used in marmosets by orders of magnitude showed typical clinical symptoms. No viral DNA was detectable in the blood of those animals, but three animals seroconverted. In two of these three animals, infectious virus was sporadically isolated from saliva. This indicates that rhesus monkeys are less susceptible to calpox virus infection, which limits their use in further intervention studies with OPXV.

Induced pluripotent stem cells (iPS cells) generated by cellular reprogramming from nonhuman primates (NHPs) are of great significance for regenerative medicine and for comparative biology. Autologously derived stem cells would theoretically avoid any risk of rejection due to host-donor mismatch and may bypass the need for immune suppression post-transplant. In order for these possibilities to be realized, reprogramming methodologies that were initially developed mainly for human cells must be translated to NHPs. NHP studies have typically used pluripotent cells generated from young animals and thus risk overlooking complications that may arise from generating iPS cells from donors of other ages. When reprogramming is extended to a wide range of NHP species, available donors may be middle- or old-aged. Here we have pursued these questions by generating iPS cells from donors across the life span of the common marmoset (Callithrix jacchus) and then subjecting them to a directed neural differentiation protocol. The differentiation potential of different clonal cell lines was assessed using the quantitative polymerase chain reaction. The results show that cells derived from older donors often showed less neural marker induction. These deficits were rescued by a 24 h pretreatment of the cells with 0.5 % dimethyl sulfoxide. Another NHP that plays a key role in biological research is the chimpanzee (Pan troglodytes). iPS cells generated from the chimpanzee can be of great interest in comparative in vitro studies. We investigated if similar deficits in differentiation potential might arise in chimpanzee iPS cells reprogrammed using various technologies. The results show that, while some deficits were observed in iPS cell clones generated using three different technologies, there was no clear association with the vector used. These deficits in differentiation were also prevented by a 24 h pretreatment with 0.5 % dimethyl sulfoxide.

Daily travel distance (DTD), the distance an animal moves over the course of the day, is an important metric in movement ecology. It provides data with which to test hypotheses related to energetics and behaviour, e.g. impact of group size or food distribution on DTDs. The automated tracking of movements by applying GPS technology has become widely available and easy to implement. However, due to battery duration constraints, it is necessary to select a tracking-time resolution, which inevitably introduces an underestimation of the true underlying path distance. Here we give a quantification of this inherent systematic underestimation of DTDs for a terrestrial primate, the Guinea baboon. We show that sampling protocols with interval lengths from 1 to 120 min underestimate DTDs on average by 7 to 35 %. For longer time intervals (i.e. 60, 90, 120 min), the relative increase of deviation from the "true" trajectory is less pronounced than for shorter intervals. Our study provides first hints on the magnitude of error, which can be applied as a corrective when estimating absolute DTDs in calculations on travelling costs in terrestrial primates.

In times of increasing costs for health insurances, obstructive lung diseases are a burden for both the patients and the economy. Pulmonary symptoms of asthma and chronic obstructive pulmonary disease (COPD) are similar; nevertheless, the diseases differ in pathophysiology and therapeutic approaches. Novel therapeutics are continuously developed, and nonhuman primates (NHPs) provide valuable models for investigating novel biologicals regarding efficacy and safety. This review discusses the role of nonhuman primate models for drug development in asthma and COPD and investigates whether alternative methods are able to prevent animal experiments.

We report observations on fur-rubbing with leaves from Piper aduncum by a San Martín titi monkey, Callicebus oenanthe. Fur-rubbing occurred during the transition from the dry to the rainy season in a titi monkey group living in a forest fragment in the Moyobamba region of Peru. Since Piper leaves include very potent compounds that may affect ectoparasites, we tentatively interpret the observed fur-rubbing as self-medication.

Endometriosis is a poorly understood common debilitating women's reproductive disorder resulting from proliferative and ectopic endometrial tissue associated with variable clinical symptoms including dysmenorrhea (painful menstrual periods), dyspareunia (pain on intercourse), female infertility, and an increased risk of malignant transformation. The rhesus macaque (Macaca mulatta) develops a spontaneous endometriosis that is very similar to that seen in women. We hypothesized that specific major histocompatibility complex (MHC) alleles may contribute to the pathogenesis of endometriosis. As part of a collaboration between the Biomedical Primate Research Centre (BPRC) in the Netherlands and the New England Primate Research Center (NEPRC) in the United States, we analyzed DNA sequences of MHC class I (Macaca mulatta, Mamu-A1) and class II (Mamu-DRB) alleles from rhesus macaques with endometriosis and compared the allele frequencies with those of age-matched healthy macaques. We demonstrate that two MHC class I alleles are overrepresented in diseased macaques compared to controls: Mamu-A1*001, 33.3 % in BPRC animals with endometriosis vs. 11.6 % in healthy macaques ( $p=$  0.007), and Mamu-A1*007, 21.9 % NEPRC rhesus macaques vs. 6.7 %, ( $p=$  0.003). We provide evidence that select MHC class I alleles are associated with endometriosis in rhesus macaques and suggest that the disease pathogenesis contribution of MHC class I warrants further research.

Human immunodeficiency virus (HIV) comorbidities have become clinically more important due to antiretroviral therapy. Although therapy increases life expectancy, it does not completely suppress immune activation and its associated complications. The simian immunodeficiency virus (SIV)-infected rhesus macaque (Macaca mulatta) represents a valuable model for the investigation of SIV-associated diseases. Although cardiovascular (CV) changes are common in HIV-infected patients, there are only a few reports on the incidence of CV findings in SIV-infected animals. In addition, potential associations between pathohistological findings and hematological parameters are still unclear. We therefore conducted a retrospective analysis of 195 SIV-infected rhesus macaques that were euthanized with AIDS-related symptoms at the German Primate Center, Goettingen, over a 25-year period. Pathological findings were correlated with hematological data. The main findings included myocarditis (12.8 %), endocarditis (9.7 %), and arteriopathy (10.3 %) in various organs. Thrombocytopenia occurred more frequently in macaques with endocarditis or arteriopathy than in macaques without CV disease (80 % in animals with endocarditis, 60 % in animals with arteriopathy, $p<0.0001$ and $p=0.0016$ , respectively). Further investigations of the interaction between coagulation markers, proinflammatory cytokines, and biomarkers associated with endothelial dysfunction (e.g., D-dimers) and histological data (vascular wall structure) may unravel the mechanisms underlying HIV/SIV-associated CV comorbidities.

In this paper we report on two encounters between olive baboons (Papio anubis) and crowned eagles (Stephanoaetus coronatus) at Lake Manyara National Park, northern Tanzania. During these encounters olive baboons responded by giving alarm calls and all infants and juveniles rushed down from trees seeking cover under bushes or close proximity to adult conspecifics. In one of the events, alarm calls from banded mongoose (Mungos mungo) and rock hyraxes (Procavia capensis) most likely triggered alarm calling of vervet monkeys (Chlorocebus pygerythrus) which in turn prompted baboons to respond with alarm calls as well. In both observations, adult male baboons took the lead in climbing trees, threatening the eagle (staring, yawning, ground slapping) and chasing it away. The reaction of the baboons suggests that crowned eagles pose a threat at least for juvenile baboons at Lake Manyara National Park.

To safeguard patients, regulatory authorities require that new drugs that are to be given by the intravitreal (IVT) route are assessed for their safety in a laboratory species using the same route of administration. Due to the high similarity of ocular morphology and physiology between humans and nonhuman primates (NHPs) and due to the species specificity of many biotherapeutics, the monkey is often the only appropriate model. To this end, intravitreal administration and assessment of ocular toxicity are well established in cynomolgus monkeys (Macaca fascicularis). In contrast, the common marmoset monkey (Callithrix jacchus) is not a standard model for ocular toxicity studies due to its general sensitivity to laboratory investigations and small eye size. It was the purpose of the present work to study whether the marmoset is a useful alternative to the cynomolgus monkey for use in intravitreal toxicological studies. Six marmoset monkeys received repeated (every 2 weeks for a total of four doses) intravitreal injections of 10 or 20  $\mu$ L of a placebo. The animals were assessed for measurements of intraocular pressure (IOP), standard ophthalmological investigations and electroretinography (ERG). At the end of the dosing period, the animals were sacrificed and the eyes were evaluated histologically. ERG revealed similar results when comparing predose to end-of-study data, and there was no difference between the two dose volumes. A transient increase in the IOP was seen immediately after dosing, which was more pronounced after dosing of 20  $\mu$ L compared to 10  $\mu$ L. Ophthalmologic and microscopic observations did not show any significant changes. Therefore, it can be concluded that 10  $\mu$ L as well as 20  $\mu$ L intravitreal injections of a placebo are well tolerated in the marmoset. These results demonstrate that the common marmoset is an alternative to the cynomolgus monkey for intravitreal toxicity testing.

Several cases of spontaneous endometriosis in middle-aged to old rhesus macaques (Macaca mulatta) from the breeding colony of the German Primate Center were thoroughly characterized with regards to anatomical distribution and macroscopic appearance, histological differentiation and immunohistochemical profile including somatic markers, hormonal receptors, and proliferation indices. More than half of the examined animals (five of nine) were directly related to one breeding male, supporting a strong genetic predisposition. Histologically, four different types of endometriotic lesions, depending on the degree of ectopic endometrial gland and stromal differentiation (well differentiated, purely stromal, mixed differentiation, poorly differentiated), could be constantly identified within all animals. Immunohistochemistry (IHC) of cytokeratin (CK), vimentin, smooth muscle actin (SMA), desmin, estrogen (ER), and progesterone (PR) receptors as well as of the nuclear proteins Ki67 and p53 revealed varying staining patterns in the four different types of endometriosis differentiation and compared to normal endometrium. Purely stromal, mixed, or poorly differentiated lesions, especially, showed additional cytokeratin-positive stromal cells, whereas epithelial cells of endometriosis with mixed or poor differentiation increasingly expressed mesenchymal markers (vimentin, SMA). Hormonal receptor and Ki67 expression in well-differentiated endometriotic lesions mostly reflected that of normal endometrial tissue according to the cyclic phase of the animal, while the expression gradually diminished with decreasing grade of differentiation. However, increased nuclear accumulations of p53 antigen could only be continuously detected in epithelial cells of mixed or poorly differentiated endometriosis. Altogether, these findings support the pathogenetic theory of coelomic metaplasia, since the expression profiles of somatic markers in less differentiated forms closely resembled that of mesothelial cells. Thus, the four different histological types of endometriosis might display subsequent grades of differentiation in the course of time, with poorly differentiated types representing newly formed, immature lesions and well-differentiated types being older, fully differentiated forms, rather than being the outcome of dedifferentiation processes.