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Cloning by somatic cell nuclear transfer (SCNT) remained challenging for Rhesus monkeys, mostly due to its low efficiency and neonatal death. Genome-scale analyses revealed that monkey SCNT embryos displayed widespread DNA methylation and transcriptional alterations, thus including loss of genomic imprinting that correlated with placental dysfunction. The transfer of inner cell masses (ICM) from cloned blastocysts into ICM-depleted fertilized embryos rescued placental insufficiency and gave rise to a cloned Rhesus monkey that reached adulthood without noticeable abnormalities.

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BACKGROUND: Documentation of lingual tumors is scarce in nonhuman primates. METHODS: Through a multi-institutional retrospective study we compile cases of primary and metastatic neoplasia in non-human primates. RESULTS: We describe five cases of lingual neoplasia. Three cases are primary lingual tumors: chondro-osteoblastic lipoma in a howler monkey, squamous cell carcinoma, and fibroma in two baboons. We describe two cases of metastatic lymphoma in the tongue in rhesus macaques. A literature review of published lingual neoplasia in nonhuman primates is included in this manuscript. CONCLUSION: Lingual neoplasia is seldom reported in non-human primates.

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Environmental enrichment improves captive animal welfare by reducing stress-related behaviors. Previous studies in a captive colony of stumptail macaques (Macaca arctoides) reported a reduction of aggression, coprophilia, and stereotypic behaviors after an occupational enrichment program; however, the effect on stress hormones such as glucocorticoids has not been investigated yet. The goal of this study was to compare the effect of sex, age, and social rank on changes in fecal glucocorticoid metabolites (fGCM) after applying two kinds of enrichments (occupational vs. musical) in a captive colony of stumptail macaques. We collected 234 fecal samples from 25 stumptail macaques under the following conditions: (1) basal (no enrichment), (2) three weeks of occupational enrichment, and (3) three weeks of relaxing/classical music. The Generalized Estimated Equation Model showed an increase in fGCM levels after the occupational enrichment only in adult subjects (p = 0.003 compared to basal). The fGCM levels reached by the adults after the occupational enrichment was higher than that of juveniles (p = 0.002) and subadults (p = 0.02). Occupational and musical enrichment decreased fGCM levels only in middle-ranking individuals (p < 0.001 and p = 0.013, respectively). No sex differences were found. In conclusion, there were age and rank differences in individuals' physiological reactivity to the effects of environmental enrichment which need to be considered when planning enrichment programs.

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The "challenge hypothesis" predicts higher male-male aggressive behavior along with increases in testosterone levels during times of reproductive challenges and social instability. In addition, in some primate species, higher glucocorticoid levels can be observed as well, but this is usually modulated by dominance rank. We studied rank-related aggressive behavior, mating activity, and fecal testosterone and glucocorticoid metabolites (fTm and fGCm) in male stumptail macaques (Macaca arctoides) in order to test some predictions of the "challenge hypothesis". Over a 20-month period, we collected data on aggressive behavior and copulation, as well as fecal samples (n = 700) to quantify fTm and fGCm in seven adult stumptail males living in captivity. During periods of mating activity, male-to-male aggression increased in higher- and middle-ranking males. Neither fTm nor fGCm levels predicted male-to-male aggression. fGCm levels (but not fTm) were positively associated with male-to-female aggression; however, this association was pronounced during periods of mating activity. fGCm levels differed according to social rank, with middle-ranking males having the highest levels. Both hormones were higher during periods of mating activity, but only in higher- and middle-ranking males. Taken together, our findings partially support the challenge hypothesis in a non-seasonal primate and shed some light on the unique social and mating system of the stumptail macaque.

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Measles infections can cause significant morbidity and mortality in human and monkey populations. The endemicity of measles in human populations and viral circulation within populations of free-living monkeys may have important repercussions for potential zoonotic transmission events and for the long-term health of monkey populations. Yet, there has not yet been a rigorous investigation of the dynamics of measles transmission where human and monkey populations coexist. In this study, to determine the difference in seroprevalence of the measles virus across different contexts of human-monkey contact, we analyzed serum samples collected from 56 apparently healthy Macaca mulatta monkeys who occupied diverse contexts, with different degrees of human-monkey contact, in Bangladesh. This is the first report of measles virus seroprevalence in monkeys in Bangladesh. We found a clear association between measles virus seropositivity in monkeys and the context in which they interact with humans. Seroprevalence was the lowest in wild areas (0.0%) and increased in shrines (4.8%), urban areas (5.9%), and was highest among monkeys who are used as performance animals (50.0%). This work suggests that a One Health approach informed by local interspecies transmission dynamics is necessary to develop strategies that both improve measles vaccination coverage, achieve long-term surveillance in monkey populations, and prevent measles spillback to monkeys. This approach aims to inform conservation efforts and protect the long-term health of human and monkey populations.

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Congenital digital defects, particularly adactyly and oligodactyly, have been reported frequently in humans, however, their occurrence in rhesus monkeys is rare, mainly in the hind limbs. We present here for the first time, two female rhesus monkeys with unilateral congenital toe defects with metatarsal involvement. One showing adactyly and the other oligodactyly. In this report, we present the clinical/radiological details of these cases as well as discuss the risk factors possibly involved, such as contact with pesticides and genetic factors.

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Climate change is increasing the frequency and intensity of weather-related disasters such as hurricanes, wildfires, floods, and droughts. Understanding resilience and vulnerability to these intense stressors and their aftermath could reveal adaptations to extreme environmental change. In 2017, Puerto Rico suffered its worst natural disaster, Hurricane Maria, which left 3,000 dead and provoked a mental health crisis. Cayo Santiago island, home to a population of rhesus macaques (Macaca mulatta), was devastated by the same storm. We compared social networks of two groups of macaques before and after the hurricane and found an increase in affiliative social connections, driven largely by monkeys most socially isolated before Hurricane Maria. Further analysis revealed monkeys invested in building new relationships rather than strengthening existing ones. Social adaptations to environmental instability might predispose rhesus macaques to success in rapidly changing anthropogenic environments.

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HLA-G allele frequencies were studied in Yucatán (Mexico) Maya Amerindians by a direct exon DNA sequencing technique. It is described that Mayas are probably one of the first populations together with Olmecs that populated Meso America and that important HLA genetic differences between Mexican and Guatemalan Mayas support that Maya languages were imposed to several neighbouring Amerindian groups. HLA-G*01:01:02, HLA-G*01:01:01 and HLA-G*01:04:01 are the most frequent alleles in this population. It is remarkable that HLA-G*01:05N allele was not found in the population in accordance with similar results found in another Amerindians. Also, protein allele HLA-G*01:04 frequency is found not to differ to those found in another far or close living Amerindians in contrast to other World populations. It seems that while high HLA-G*01:05N frequency is found in Iran and Middle East populations, probably where this allele appeared within an ancestral HLA-A*19 group of alleles haplotype and it is maintained by unknown evolutionary forces, Amerindians do not have a high frequency because a founder effect or because required natural evolutionary forces do not exist in America. Finally, we believe useful to study HLA-G evolution for its physiopathology understanding in addition to the many papers on statistics on HLA-G and in vitro models that are yearly published.

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In a captive Macaca mulatta breeding colony, a single family group with 39 animals showed 19 individuals being born with dramatic tail shortening. Through clinical, genealogical, radiographic, and cytogenetic evaluation, it was related to a probable dominant autosomal inheritance of the reduction in the number of distal caudal vertebrae.

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Hypomelanosis of Ito is a rare neurocutaneous syndrome, characterized by streaks and swirls of hypopigmentation arranged in a Blaschkoid pattern. Other associated anomalies are observed. We report a case of a male cynomolgus monkey (Macaca fascicularis) who presented the characteristic of hypomelanosis of Ito with palmoplantar involvement and polythelia.

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We are currently living the advent of a new age for medicine in which basic research is being quickly translated into marketable drugs, and the widespread access to genomics data is allowing the design and implementation of personalized solutions to medical conditions. Non-human primates (NHP) have gained an essential role in drug discovery and safety testing due to their close phylogenetic relationship to humans. In this study, a collection of well characterized genes of the human immune system was used to define the orthology-based immunome in four NHP species, with carefully curated annotations available based on multi-tissue RNA-seq datasets. A broad variation in the frequency of expressed protein isoforms was observed between species. Finally, this analysis also revealed the lack of expression of at least four different chemokines in new-world primates. In addition, transcripts corresponding to four genes including interleukin 12 subunit alpha were expressed in humans but no other primate species analyzed. Access to the non-human primate immunome is available in http://www.fidic.org.co:90/proyecto/.

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Purpose: To evaluate the toxicity of Erbitux as well as its biosimilar APZ001 antibody (APZ001) in pre-clinical animal models including mice, rabbits and cynomolgus monkeys. Methods: We performed analysis of normal behavior activity, autonomic and non-autonomic nervous functions, nervous-muscle functions, nervous excitability and sensorimotor functions on CD-1 mice. Subsequently, we studied that effects of APZ001 and Erbitux on respiratory system, cardiovascular system and kidney in Cynomolgus monkey models and performed local tolerance experiments on New Zealand rabbits. Results: The comparisons between APZ001 and Erbitux showed no significant differences in mice autonomic nervous system, nervous muscle functions, non-autonomic nervous functions, nervous excitability and sensorimotor functions between treated and untreated group (p>0.05). APZ001 and Erbitux showed negative effect on CD-1 mice in the present of pentobarbital sodium anesthesia (p>0.05). Single administrations of high, medium or low doses of APZ001 did not lead to monkey urine volume alterations (p>0.05). In human tissues, APZ001 and Erbitux showed positive signals in endocardium, lung type II alveolar epithelial cell and surrounding vessels, but showed negative results in kidney and liver tissues. No hemolysis phenomenon and serious side-effects in vessels and muscles were observed in rabbits when administrated with APZ001 and Erbitux respectively. Conclusion: The safety comparisons between APZ001 antibody and Erbitux showed that these two antibodies showed highly similarities in mice, rabbits and cynomolgus monkey animal models in consideration of pharmaceutical effects, indicating APZ001 might be a suitable substitute for Erbitux.(AU)

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Abstract Purpose: To evaluate the toxicity of Erbitux as well as its biosimilar APZ001 antibody (APZ001) in pre-clinical animal models including mice, rabbits and cynomolgus monkeys. Methods: We performed analysis of normal behavior activity, autonomic and non-autonomic nervous functions, nervous-muscle functions, nervous excitability and sensorimotor functions on CD-1 mice. Subsequently, we studied that effects of APZ001 and Erbitux on respiratory system, cardiovascular system and kidney in Cynomolgus monkey models and performed local tolerance experiments on New Zealand rabbits. Results: The comparisons between APZ001 and Erbitux showed no significant differences in mice autonomic nervous system, nervous muscle functions, non-autonomic nervous functions, nervous excitability and sensorimotor functions between treated and untreated group (p>0.05). APZ001 and Erbitux showed negative effect on CD-1 mice in the present of pentobarbital sodium anesthesia (p>0.05). Single administrations of high, medium or low doses of APZ001 did not lead to monkey urine volume alterations (p>0.05). In human tissues, APZ001 and Erbitux showed positive signals in endocardium, lung type II alveolar epithelial cell and surrounding vessels, but showed negative results in kidney and liver tissues. No hemolysis phenomenon and serious side-effects in vessels and muscles were observed in rabbits when administrated with APZ001 and Erbitux respectively. Conclusion: The safety comparisons between APZ001 antibody and Erbitux showed that these two antibodies showed highly similarities in mice, rabbits and cynomolgus monkey animal models in consideration of pharmaceutical effects, indicating APZ001 might be a suitable substitute for Erbitux.

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Objetivo: A campilobacteriose é uma das principais doenças entéricas do mundo. Ocorre não só no homem mas também em primatas não humanos, sendo desta forma importante no monitoramento sanitário de colônias de animais provenientes de criatórios científicos. É causada por bactérias do gênero Campylobacter, cuja detecção em biotérios possibilita não só controlar a doença e prevenir sua disseminação, mas assegurar a qualidade das pesquisas que serão realizadas nestes biomodelos. Com base na importância deste isolamento, nosso objetivo foi a verificação do status sanitário de uma colônia de criação de Macaca mulatta, usando como referência a presença de Campylobacter spp. Métodos: Durante o manejo médico anual coletaram-se 52 swabs fecais de primatas não humanos adultos, o que representou um percentual de 10% da colônia total. Esse material foi submetido ao esquema de semeadura/incubação e identificação de Campylobacter sp. seguindo as recomendações de cultivo microbiológico, incluindo o isolamento, prova de Gram e testes bioquímicos. Todo o processo levou de cinco a sete dias e foi realizado em atmosfera de microaerofilia. Resultados: Em 14 indivíduos foram isoladas bactérias do gênero Campylobacter. Destes, sete eram portadores de Campylobacter coli, seis portadores de Campylobacter jejuni e em um indivíduo não foi possível definir a espécie de Campylobacter isolada. Conclusão: Apesar da baixa prevalência (27%), esses resultados reforçam a necessidade de constante monitoramento microbiológico dos primatas pertencentes à colônia, visando não só a qualidade dos animais fornecidos, mas minimizando o risco de contaminação dentro da colônia e de contágio pelos profissionais que lidam com os animais, já que o Campylobacter possui importante potencial zoonótico.

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Although the breeding seasonality in Macaca arctoides have been studied over a long period of time, it is still controversial whether reproduction in this primate tend to increase during certain months of the year as it happens in most of the macaque species. Many authors have classified Macaca arctoides as not being seasonal species. Nonetheless, there were no reports, about seasonal variations of female sexual hormones to demonstrate that asseveration. Therefore, in the present study we collect 1611 fecal samples from June 2009 to November 2010 from 10 female stump-tailed macaques to measure 17ß-estradiol and progesterone concentrations. Also, we included the birth frequency per year, in order to identify if sexual hormones peaked at a certain period of the year, thus, births would be occurring six months later according to the gestation length of stump-tailed macaques. Our results indicate two mating seasons per year in stump-tailed macaques: one in July-August and a second one in November. The distribution of the birth frequency, throughout the year support these results. We conclude that stump-tail macaques have a discrete seasonality no different than most of macaques' species.

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Complicações reprodutivas de primatas não humanos (PNH) têm sido detectadas em criações animais, tornando-se comumente necessário separar o filhote da mãe. Este trabalho descreve incidência, origem e perfil de casos de macacos rhesus (Macaca mulatta) lactentes mantidos em berçário em um criatório científico, visando enfatizar a importância dos cuidados neonatais, e de como o manejo reflete sobre o desenvolvimento saudável dos animais e o sucesso da reintrodução destes em grupos familiares. Foi realizado um estudo retrospectivo, no período de 2008 a 2017, de 25 macacos rhesus lactentes que receberam cuidados neonatais. As informações foram obtidas em um banco de registros da criação. No período de nove anos, foram recebidos no berçário 25 filhotes de M. mulatta, sendo 52% de machos (13/25) e 48% de fêmeas (12/25), e desses, 28% (7/25) vieram a óbito, enquanto 72% (18/25) dos animais sobreviveram. Todos os filhotes sobreviventes foram reintroduzidos ao convívio social. As análises do trabalho demonstraram que em um criatório de PNH, diversos fatores podem comprometer a convivência da mãe e filhote, resultando na necessidade de um ambiente preparado com equipamento, material e mão de obra especializada para atendimento dos lactentes afastados de suas mães. Além disso, o planejamento adequado da reaproximação do filhote ao grupo familiar deve ser realizado objetivando minimizar as alterações comportamentais e sucesso no convívio social.

Reproductive complications of nonhuman primates (NHP) have been detected in animal breeding, which becomes commonly necessary separating the baby from the mother. This paper describes the incidence, origin, and profile cases of nursling rhesus macaques (Macaca mulatta) kept in nursery unit from a scientific creation, with the aims of emphasizing the importance of neonatal care, how the management reflects on the healthy development of the animals, as well as the success of reintroducing them into family groups. A retrospective study was carried out, from 2008 to 2017, of 25 infant rhesus macaques who received neonatal care. Data were obtained from a database of the breeding records. During nine years 25 nursling M. mulatta were received in the neonatal care section, with 52% (13/25) of males and 48% (12/25) of females, and from these, 28% (7/25) died, while 72% (18/25) of the animals have survived. All the surviving infants were reintroduced into social interaction. Work analyzes demonstrated that in a NHP creation several factors could compromise the living together between the mother and its offspring, resulting in the need of a prepa-red environment with equipment, material, and specialized labor to attend the infants away from their mothers. In addition, adequate planning about rapprochement of the infant to the family group should performed with the purpose of minimizing behavioral alterations and obtaining success on the social life.

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Complicações reprodutivas de primatas não humanos (PNH) têm sido detectadas em criações animais, tornando-se comumente necessário separar o filhote da mãe. Este trabalho descreve incidência, origem e perfil de casos de macacos rhesus (Macaca mulatta) lactentes mantidos em berçário em um criatório científico, visando enfatizar a importância dos cuidados neonatais, e de como o manejo reflete sobre o desenvolvimento saudável dos animais e o sucesso da reintrodução destes em grupos familiares. Foi realizado um estudo retrospectivo, no período de 2008 a 2017, de 25 macacos rhesus lactentes que receberam cuidados neonatais. As informações foram obtidas em um banco de registros da criação. No período de nove anos, foram recebidos no berçário 25 filhotes de M. mulatta, sendo 52% de machos (13/25) e 48% de fêmeas (12/25), e desses, 28% (7/25) vieram a óbito, enquanto 72% (18/25) dos animais sobreviveram. Todos os filhotes sobreviventes foram reintroduzidos ao convívio social. As análises do trabalho demonstraram que em um criatório de PNH, diversos fatores podem comprometer a convivência da mãe e filhote, resultando na necessidade de um ambiente preparado com equipamento, material e mão de obra especializada para atendimento dos lactentes afastados de suas mães. Além disso, o planejamento adequado da reaproximação do filhote ao grupo familiar deve ser realizado objetivando minimizar as alterações comportamentais e sucesso no convívio social.(AU)

Reproductive complications of nonhuman primates (NHP) have been detected in animal breeding, which becomes commonly necessary separating the baby from the mother. This paper describes the incidence, origin, and profile cases of nursling rhesus macaques (Macaca mulatta) kept in nursery unit from a scientific creation, with the aims of emphasizing the importance of neonatal care, how the management reflects on the healthy development of the animals, as well as the success of reintroducing them into family groups. A retrospective study was carried out, from 2008 to 2017, of 25 infant rhesus macaques who received neonatal care. Data were obtained from a database of the breeding records. During nine years 25 nursling M. mulatta were received in the neonatal care section, with 52% (13/25) of males and 48% (12/25) of females, and from these, 28% (7/25) died, while 72% (18/25) of the animals have survived. All the surviving infants were reintroduced into social interaction. Work analyzes demonstrated that in a NHP creation several factors could compromise the living together between the mother and its offspring, resulting in the need of a prepa-red environment with equipment, material, and specialized labor to attend the infants away from their mothers. In addition, adequate planning about rapprochement of the infant to the family group should performed with the purpose of minimizing behavioral alterations and obtaining success on the social life.(AU)

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This article presents a pictorial history of the free-ranging colony of rhesus monkeys (Macaca mulatta) on Cayo Santiago, Puerto Rico, in commemoration of the 75th anniversary of its establishment by Clarence R. Carpenter in December 1938. It is based on a presentation made by the authors at the symposium, Cayo Santiago: 75 Years of Leadership in Translational Research, held at the 36th Annual Meeting of the American Society of Primatologists in San Juan, Puerto Rico, on 20 June 2013.

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Cayo Santiago is the oldest continuously operating free-ranging rhesus monkey colony in the world. Population control of this colony has historically been carried out by periodic live capture and removal of animals. However, the effect of such a strategy on the size, growth rate, age structure, and sex ratio of the population has not been analyzed. This study reviews past removal data and uses a population projection model to simulate the effects of different removal schemes based on Cayo Santiago demographic data from 2000-2012. The model incorporates negative density-dependence in female fertility, as well as male and female survival rates, to determine the population-level effects of selective removal by age and sex. Modeling revealed that removal of sexually immature individuals has negligible effects on the population dynamics explaining why with an initial population of 1309 in 2000 and annual removals of immature monkeys a mean annual population growth rate of 12% and a final population size of ∼1,435 individuals by 2012 (∼0.009 animal/m(2) ) was observed. With no removals, the population is expected to exhibit dampened oscillations until reaching equilibrium at ∼1,690 individuals (∼0.0111 animal/m(2) ) in 2,100. In contrast, removal of adult females (≥4 yrs) would significantly reduce the population size, but would also promote an increase in population growth rate due to density feedback. A maximum annual production of 275 births is expected when 550 adult females are present in the population. Sensitivity analyses showed that removing females, in contrast to controlling their fertility through invasive treatments would contribute the most to changes in population growth rate. Given the density compensation on fertility, stabilizing the population would require removing ∼80% of the current population of adult females. This study highlights the importance of addressing the population-level density effects, as well as sensitivity analyses, to optimize management strategies.

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Reproductive synchrony and the consequent clustering of births are hypothesized to be regulated by seasonal changes in rainfall and food availability. Such climate-related seasonality is, however, questionable in tropical populations occupying temporally invariant habitats year round. Using the long-term data of the Cayo Santiago rhesus macaques from 1973 to 2013, this study distinguishes synchrony (a greater than chance clustering of births) from seasonality (a cluster of births during a period of the year when abiotic conditions are favorable) and shows that females are highly synchronized (>72% of births in a 3-month period) but the effects of environmental zeitgebers on reproduction are overridden by biological factors. Specifically, biotic and abiotic factors including (i) loss of immature offspring; (ii) population density; (iii) age at delivery; (iv) rainfall; and (v) changes in colony management were modeled in relation to the annual onset of births and the median birth date. Females experiencing loss of immature offspring had an interbirth interval of <365 days in average and the proportion of these females increased up to 48% due to changes in colony management overtime, although reproductive synchrony increased with increasing population density. A secular trend in both the onset of births and the median date of birth is documented and the model predicts that the median birth date will advance across all calendar-based seasons by 2050. The secular trend in reproduction appears to be triggered by changes in the age at delivery of females, the absence of physiological constraints from maternal investment due to offspring loss, shorter interbirth interval, and a higher degree of coordination due to increasing population density. This study challenges the reproductive phenology previously described for rhesus macaques highlighting the importance of long-term studies in addressing the ultimate causes of reproductive synchrony.

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