Epigenetic plasticity following early stress predicts long-term health outcomes in rhesus macaques

Early life stress has been linked with poorer lifelong health outcomes across species, including modern and ancient humans. Epigenetic mechanisms, such as DNA methylation patterning of stress pathway genes in stress-responsive tissue, may play an important role in the long-term health effects of early stress across species. The relationships among early maternal care quality, DNA methylation patterns in a candidate stress pathway gene (serotonin transporter, 5-HTT) linked region in blood DNA, and adult health outcomes were examined in male and female rhesus macaques, excellent models of human health. Male (n = 12) and female (n = 32) infants were observed with their mothers for the first 12 weeks of life and 5-HTT linked DNA methylation was measured in blood at 12 weeks of age. Approximately 8 years later, health-related measures were collected for the 25 animals (6 male and 19 female) that were available for study. Health composite scores were generated using factor analysis of body condition, body weight, and diagnosis of diarrhea during the lifespan. Better quality maternal care predicted lower 5-HTT linked methylation at 12 weeks of age. Lower 5-HTT methylation, in turn, predicted better health composite scores in adulthood, including better body condition, greater body weight and absence of lifetime diarrhea. These data suggest that the epigenetic regulation of 5-HTT may be one biomarker of the link between early stress and lifetime health trajectories. Future studies will examine whether epigenetic signatures in modern and ancient human DNA lends insight into stress and health and natural selection in human evolutionary history. Am J Phys Anthropol 155:192–199, 2014. © 2014 Wiley Periodicals, Inc.     

Neonatal nipple preference and maternal cradling laterality in wild Taihangshan macaques (Macaca mulatta tcheliensis)

Lateralized behavior is considered an observable phenotype of cerebral functional asymmetry and has been documented in many mammalian species. In the present study, we examined evidence of lateralization in neonatal nipple contact, maternal cradling, and the relationship between these two behaviors during the first 12 weeks of life in wild Taihangshan macaques (Macaca mulatta tcheliensis). The results showed that across our sample of nine mother–infant dyads: (1) Seven of nine neonates exhibited a significant left-side nipple preference during the first 12 weeks of life, whereas eight of nine mothers displayed a significant right-side cradling preference; (2) at the population level, there was a significant preference for left nipple contact by neonatal Taihangshan macaques and a significant right-hand maternal cradling preference; (3) at the population level, there was a nonsignificant negative correlation between neonatal nipple preference and maternal cradling bias; and (4) the strength of individual neonatal nipple preference and maternal cradling laterality were not correlated. We conclude that asymmetry in nipple contact of Taihangshan macaques occurs early in behavioral development. Given that infant Taihangshan macaques are able to nurse and cling unassisted to their mothers within a few days after birth, it appears that the infant rather than its mother is responsible for determining a nipple-side preference. Our results indicating a left-side nipple bias in 78% of wild neonatal Taihangshan macaques are most consistent with the heartbeat hypothesis.     

Alopecia in Rhesus macaques correlates with immunophenotypic alterations in dermal inflammatory infiltrates consistent with hypersensitivity etiology

Background Although alopecia is a commonly recognized problem affecting many captive Rhesus macaque colonies, there is no consensus as to the underlying etiology or appropriate course of management. Methods We performed skin biopsies to assess underlying pathology in alopecic Rhesus macaques and performed immunohistochemical and metachromatic staining of these biopsies to assess the cellular infiltrates. Results Alopecia is associated with superficial dermal perivascular mononuclear cell infiltrates and skin pathology consistent with chronic hypersensitivity dermatitis. The inflammation is primarily composed of CD4+ cells admixed with histiocytes and mast cells. Inflammation is correlated with degree of alopecia. Further analysis in different groups of macaques revealed that animals born outdoors or infected with lung mites had reduced dermal inflammatory cell infiltrates and a lower incidence of alopecia. Conclusions These findings support a hypothesis that an altered housing status resulting in decreased pathogen burden in Rhesus macaque colonies may contribute to dermal immunophenotypic alterations and subsequent development of dermatitis with resultant alopecia.     

ORIGINAL ARTICLE: Epithelioid hemangioendothelioma in the right auricle of an adult,male Rhesus macaque (Macaca mulatta)

Abstract Background A 9‐year‐old, male castrate, Rhesus macaque was euthanized following a prolonged history of chronic renal failure. Results Necropsy revealed a proliferative lesion within the right cardiac auricle composed of neoplastic epithelioid cells which infiltrated the myocardium and frequently exhibited intracytoplasmic luminae. Cells multifocally exhibited strong cytoplasmic immunoreactivity for Factor VIII‐related protein (von Willebrand’s factor). Conclusions The histological characteristics of this tumor are consistent with a diagnosis of epithelioid hemangioendothelioma, an intermediate‐grade vasoformative neoplasm which has to our knowledge not previously been reported in the heart of a non‐human species.     

Pathogenic analysis of coxsackievirus A10 in rhesus macaques

Coxsackievirus A10 (CV-A10) is one of the etiological agents associated with hand, foot and mouth disease (HFMD) and also causes a variety of illnesses in humans, including pneumonia, and myocarditis. Different people, particularly young children, may have different immunological responses to infection. Current CV-A10 infection animal models provide only a rudimentary understanding of the pathogenesis and effects of this virus. The characteristics of CV-A10 infection, replication, and shedding in humans remain unknown. In this study, rhesus macaques were infected by CV-A10 via respiratory or digestive route to mimic the HFMD in humans. The clinical symptoms, viral shedding, inflammatory response and pathologic changes were investigated in acute infection (1–11 day post infection) and recovery period (12–180 day post infection). All infected rhesus macaques during acute infection showed obvious viremia and clinical symptoms which were comparable to those observed in humans. Substantial inflammatory pathological damages were observed in multi-organs, including the lung, heart, liver, and kidney. During the acute period, all rhesus macaques displayed clinical signs, viral shedding, normalization of serum cytokines, and increased serum neutralizing antibodies, whereas inflammatory factors caused some animals to develop severe hyperglycemia during the recovery period. In addition, there were no significant differences between respiratory and digestive tract infected animals. Overall, all data presented suggest that the rhesus macaques provide the first non-human primate animal model for investigating CV-A10 pathophysiology and assessing the development of potential human therapies.     

贵州黔灵山公园半野生的猕猴的种群动态

科学分析动物种群增长动态,合理确定环境容量是管控城市半野生动物种群激增危害的根本途径。本文对贵州贵阳黔灵山公园半野生猕猴种群特征、种群增长、环境容纳量以及猴群对公园的危害进行了研究分析。结果表明：（1）较之野生种群,园内栖息种群密度高、猴群大。现有8个稳定猴群共计1067只[最小群：47只;最大群：226只,平均：（133±67）只],总体雌雄性比为1.33;全区种群密度约达251只/km²,但猴群主要栖息于游道及其周边,导致主分布区密度高达 2134只/km2;（2）种群增长迅速、繁殖力旺盛。自1992年以来,种群呈指数型增长（年均增长率为8.08%,增长函数为y=30.6789*exp[(x-1987)/8.7894+ 64.0193),当前种群总体年龄结构为成年猴>青年猴>幼年猴,虽青幼个体数量较成年个体少,但成年雌雄性比达到1.50,性成熟个体较多,有效种群数大,仍保持旺盛的繁殖力;（3）种群Logistic增长曲线（y=792/(1+2.8495E+183*exp-0.2104x）表明园内环境容量（K值）为792只,与该区猕猴伤人事件频率曲线进入高位平台期所对应的种群数量接近。文中还对猴群栖息对当地植物多样性造成的影响进行了调查。调查监测表明,种群过大且集中栖息导致公园内生物多样性破坏、人猴冲突、公共健康隐患等一系列问题产生,建议应通过节育、分流等相关措施,将种群数量控制在K/2即400只左右为宜。本文可为黔灵山公园猕猴保护管理及其他城市野生动物管理提供参考。     

Reproductive efficiency of captive Chinese- and Indian-origin rhesus macaque (Macaca mulatta) females

Reproductive and survival records (n=2,913) from 313 Chinese-origin and 365 Indian-derived rhesus macaques at the Tulane National Primate Research Center (TNPRC) spanning three generations were studied. Least-squares analysis of variance procedures were used to compare reproductive and infant survival traits while proportional hazards regression procedures were used to study female age at death, number of infants born per female, and time from last birth to death. Chinese females were older at first parturition than Indian females because they were older when placed with males, but the two subspecies had similar first postpartum birth interval (1st PPBI) and lifetime postpartum birth interval (LPPBI). Females that gave birth to stillborn infants had shorter first postpartum birth intervals (1st PPBI) than females giving birth to live infants. Postpartum birth intervals decreased in females from age 3 to 12 but then increased again with advancing age. Chinese infants had a greater survival rate than Indian infants at 30 days, 6 months, and 1 year of age. Five hundred and forty-three females (80.01%) had uncensored, or true records for age at death, number of infants born per female, and time from the birth until death whereas 135 females (19.91%) had censored records for these traits. Low- and high-uncensored observations for age at death were 3 and 26 years for Chinese, and 3 and 23 years for Indian females. Uncensored number of infants born per female ranged from 1 to 15 for Chinese females and 1 to 18 for Indian females. Each of these traits was significantly influenced by the origin×generation interaction in the proportional hazards regression analyses, indicating that probabilities associated with age at death, number of infants born per female, and time from last birth to death for Chinese and Indian females did not rank the same across generations.     

Dominance hierarchy and social grooming in female lion- tailed macaques (Macaca silenus) in the Western Ghats, India

This article reports the structure of dominance and its relationship with social grooming in wild lion-tailed macaque females. The strength of dominance hierarchy was 0.79 on a scale of 0 to 1 indicating a moderate linearity in the ranking system. Dominance scores were converted into an ordinal as well as an interval scale. Grooming scores were also converted into interval scales using standard scores. Grooming received and grooming given correlated positively and negatively respectively with dominance ranks indicating that high ranking females received more and gave less grooming. Grooming was also positively related to encounter rates for dyads of females. More grooming among adjacent ranks, and grooming being more reciprocal, occurred only in the case of dominant females. The grooming patterns, therefore, appeared to be more of despotic than egalitarian nature. While ranking macaques into different Grades of social systems ranging from despotic to egalitarian, Thierry (2004) has placed lion-tailed macaques in Grade 3 corresponding to the ‘relaxed’ social system. Our results indicate that the grooming and dominance relationships in this species are more despotic, and hence, the Grade for this species requires to be shifted toward 2 or 1.