Periodontal disease susceptible matrilines in the Cayo Santiago Macaca mulatta macaques.

OBJECTIVE AND BACKGROUND: The expression of periodontitis, including age of onset, extent, and severity is considered to represent an interaction of the individual's oral microbiome and host response to the microbial challenge that is modified by both genetics and environmental factors. The aim of this study was to determine the distribution of periodontitis in a population of nonhuman primates, to document features of familial distribution that could reflect heritability and transmission of microbes with enhanced virulence. MATERIAL AND METHODS: This report presents our findings from evaluation of periodontal disease bone defects in skulls from 569 animals (5-31 years of age) derived from the skeletons of the rhesus monkeys (Macaca mulatta) of Cayo Santiago derived from eight matrilines over 6-9 generations. The distance from the base of alveolar bone to the cemento-enamel junction on 1st /2nd premolars and 1st /2nd molars from all four quadrants was evaluated as a measure of periodontal disease. Additionally, we documented the presence of periodontitis in 79 living descendants within these matrilines. RESULTS: The results demonstrated an increased extent and severity of periodontitis with aging across all matrilines. Extensive heterogeneity in disease expression was observed among the animals and this was linked to specific periodontitis susceptible matrilines. Moreover, we identified some matrilines in which the members appeared to show some resistance to more severe disease, even with aging. CONCLUSION: Linking these disease variations to multigenerational matriarchal family units supported familial susceptibility of periodontitis. This familial disease relationship was reinforced by the distribution of naturally-occurring periodontitis in the living descendants.

The ticking clock of Cayo Santiago macaques and its implications for understanding human circadian rhythm disorders.

The circadian clock disorders in humans remain poorly understood. However, their impact on the development and progression of major human conditions, from cancer to insomnia, metabolic or mental illness becomes increasingly apparent. Addressing human circadian disorders in animal models is, in part, complicated by inverse temporal relationship between the core clock and specific physiological or behavioral processes in diurnal and nocturnal animals. Major advantages of a macaque model for translational circadian research, as a diurnal vertebrate phylogenetically close to humans, are further emphasized by the discovery of the first familial circadian disorder in non-human primates among the rhesus monkeys originating from Cayo Santiago. The remarkable similarity of their pathological phenotypes to human Delayed Sleep Phase Disorder (DSPD), high penetrance of the disorder within one branch of the colony and the large number of animals available provide outstanding opportunities for studying the mechanisms of circadian disorders, their impact on other pathological conditions, and for the development of novel and effective treatment strategies.

Familial periodontal disease in the Cayo Santiago rhesus macaques.

Substantial ongoing research continues to explore the contribution of genetics and environment to the onset, extent and severity of periodontal disease(s). Existing evidence supports that periodontal disease appears to have an increased prevalence in family units with a member having aggressive periodontitis. We have been using the nonhuman primate as a model of periodontal disease for over 25 years with these species demonstrating naturally occurring periodontal disease that increases with age. This report details our findings from evaluation of periodontal disease in skulls from 97 animals (5-31 years of age) derived from the skeletons of the rhesus monkeys (Macaca mulatta) on Cayo Santiago. Periodontal disease was evaluated by determining the distance from the base of the alveolar bone defect to the cemento-enamel junction on 1st/2nd premolars and 1st/2nd molars from all four quadrants. The results demonstrated an increasing extent and severity of periodontitis with aging across the population of animals beyond only compensatory eruption. Importantly, irrespective of age, extensive heterogeneity in disease expression was observed among the animals. Linking these variations to multi-generational matriarchal family units supported familial susceptibility of periodontitis. As the current generations of animals that are descendants from these matrilines are alive, studies can be conducted to explore an array of underlying factors that could account for susceptibility or resistance to periodontal disease.

Demographic variability and density-dependent dynamics of a free-ranging rhesus macaque population.

Density-dependence is hypothesized as the major mechanism of population regulation. However, the lack of long-term demographic data has hampered the use of density-dependent models in nonhuman primates. In this study, we make use of the long-term demographic data from Cayo Santiago's rhesus macaques to parameterize and analyze both a density-independent and a density-dependent population matrix model, and compare their projections with the observed population changes. We also employ a retrospective analysis to determine how variance in vital rates, and covariance among them, contributed to the observed variation in long-term fitness across different levels of population density. The population exhibited negative density-dependence in fertility and the model incorporating this relationship accounted for 98% of the observed population dynamics. Variation in survival and fertility of sexually active individuals contributed the most to the variation in long-term fitness, while vital rates displaying high temporal variability exhibited lower sensitivities. Our findings are novel in describing density-dependent dynamics in a provisioned primate population, and in suggesting that selection is acting to lower the variance in the population growth rate by minimizing the variation in adult survival at high density. Because density-dependent mechanisms may become stronger in wild primate populations due to increasing habitat loss and food scarcity, our study demonstrates that it is important to incorporate variation in population size, as well as demographic variability into population viability analyses for a better understanding of the mechanisms regulating the growth of primate populations.

Long-distance transportation of primate embryos developing in culture: a preliminary study.

Non-human primate embryos are invaluable for conducting research relevant to human infertility and stem cells, but their availability is restricted. In this preliminary study, rhesus monkey embryos were produced by IVF at the Caribbean Primate Research Centre and shipped in tubes of gassed culture medium within a battery-powered transport incubator by overnight courier to Wayne State University in Michigan. Upon arrival, the embryos were incubated in fresh culture medium to evaluate further development. In 11 shipments comprising 98 cleavage-stage embryos developing from oocytes that were mature (MII) upon collection, 51 (52%) reached advanced preimplantation stages (morula to hatched blastocyst) during prolonged culture following transportation. However, most embryos produced from oocytes that were immature (MI) at collection arrested and only 5/51 (10%) reached advanced stages of development. This study demonstrates that non-cryopreserved primate embryos can be routinely transported between distant sites without loss of developmental ability. In this way, the processes of production and study of non-cryopreserved primate embryos need not be restricted to the same or nearby laboratories. This will expand the use of these embryos for research and facilitate generation of translationally relevant information.

Effects of in vitro maturation and age on oocyte quality in the rhesus macaque Macaca mulatta.

OBJECTIVE: To evaluate oocyte quality in a primate model. DESIGN: Analysis of oocyte karyotype by chromosome spreading and oocyte spindles by confocal microscopy. SETTING: Research laboratory, Caribbean Primate Research Center. ANIMAL(S): Rhesus macaques aged 6-22 years. INTERVENTION(S): Fourteen females underwent both Regimen A (FSH + hCG) and Regimen B (FSH only) stimulation cycles to facilitate collection of mature and immature oocytes. Immature oocytes from Regimens A and B underwent in vitro maturation (IVM) to produce metaphase II oocytes. All metaphase II oocytes underwent gradual fixation to spread chromosomes or were fixed and stained with probes specific to alpha-tubulin, actin, and DNA for visualization of the meiotic spindle using confocal microscopy. MAIN OUTCOME MEASURE(S): Karyotype and meiotic spindle architecture differences among in vivo matured (IVO) and IVM oocytes from young and old rhesus macaques. RESULT(S): In all, 4.7% of IVO oocytes (Regimen A) from young females were hyperhaploid versus 25.0% of IVM oocytes (Regimen B) from old females; 4.5% of IVO oocytes (Regimen A) from young females versus 51.5% of IVM oocytes (Regimen B) from old females displayed abnormal chromosome alignment on the metaphase spindle. CONCLUSION(S): IVM can induce meiotic anomalies in macaque oocytes, especially those obtained from older females. Results from this study provide possible explanations for the reported reduction in developmental competence of IVM primate oocytes.

Fatal granulomatous meningoencephalitis associated to mycobacterium mucogenicum-like microorganism: a case report.

Mycobacterium mucogenicum is rarely associated to human infections. However, in the last year, a few reports of sepsis and fatal cases of central nervous systems have been documented. Here we report a fatal case of granulomatous meningoencephalitis of three weeks of evolution where DNA from a M. mucogenicum-like microorganism was identified postmortem in samples of brain tissue.

Herpes B-virus seroreactivity in a colony of Macaca mulatta: data from the Sabana Seca Field Station, a new specific pathogen-free program.

The demand for B-virus-free animals for biomedical research is increasing, while at the same time the availability of such animals is decreasing. The establishment of Specific Pathogen-Free (SPF) breeding macaque colonies is a priority of the National Institutes of Health. Nevertheless, it is well known that seroreactivity to B-virus can be difficult to interpret, particularly as it can vary over time in a single animal. The aim of the present study was to implement a reliable algorithm to examine B-virus reactivity among the rhesus monkey population of the Caribbean Primate Research Center. The sensitivity and specificity of our assay were determined using reports from two different laboratories as references. Whereas 95.4% of animals showed consistent serological status and 4.6% of animals recruited to this SPF program showed serovariability to B-virus over the initial 2 years of examination. Implications for all SPF programs are discussed in this article.

The introduced free-ranging rhesus and patas monkey populations of southwestern Puerto Rico.

Rhesus (Macaca mulatta) and patas (Erythrocebus patas) monkeys escaped to the mainland of southwestern Puerto Rico (SWPR) from research colonies on small offshore islands during the 1960s and through 1982. A three year study (1990-1993) combined radio-telemetry with visual observations to collect information on population sizes, the composition of social groups, their daily movements, and their home ranges. Two populations of rhesus monkeys were identified in SWPR: one within the study area in Sierra Bermeja and a second population located 10 km north of the study area. The size of the Sierra Bermeja rhesus population was derived from escapees from research colonies and at the time of the study was 65-85 individuals. Within their home range area (3.7 km2) the density of this population was >>18.9 individuals/km2. A second rhesus population was found in a mountainous region 10 km north of the study area. This population consisted of one (or two) heterosexual groups with a total of 40-45 individuals. Although a primary characteristic of this species in India is its ability to live as a commensal with humans, the rhesus monkey populations of SWPR are extremely shy and elusive, they avoid contact with humans. The patas monkey population consisted of >>120 individuals in four heterosexual groups and several all-male bands. There was no evidence of patas monkeys outside the study area. Within their home ranges (26.8 km2) the population density was 4.47 individuals/km2). Patas monkeys have not previously been considered a territorial species, their behavior in SWPR suggested territoriality. In contrast to studies in Africa, where the amount of home range overlap between patas monkey groups in high, in SWPR the amount of range overlap between groups is small and each group uses areas with clearly defined boundaries.

B-virus and free-ranging macaques, Puerto Rico.

In Puerto Rico, risk for transmission of B-virus from free-ranging rhesus monkeys to humans has become a serious challenge. An incident with an injured rhesus monkey, seropositive for B-virus, resulted in inappropriate administration of antiviral postexposure prophylaxis. This incident underscores the importance of education about risks associated with interactions between humans and nonhuman primates.