OpenMonkeyChallenge: Dataset and Benchmark Challenges for Pose Tracking of Non-human Primates

The ability to automatically track non-human primates as they move through the world is important for several subfields in biology and biomedicine. Inspired by the recent success of computer vision models enabled by benchmark challenges (e.g., object detection), we propose a new benchmark challenge called OpenMonkeyChallenge that facilitates collective community efforts through an annual competition to build generalizable non- human primate pose tracking models. To host the benchmark challenge, we provide a new public dataset consisting of 111,529 annotated (17 body landmarks) photographs of non-human primates in naturalistic contexts obtained from various sources including the internet, three National Primate Research Centers, and the Minnesota Zoo. Such annotated datasets will be used for the training and testing datasets to develop generalizable models with standardized evaluation metrics. We demonstrate the effectiveness of our dataset quantitatively by comparing it with existing datasets based on seven state-of-the-art pose tracking models.

Temperament Predicts the Quality of Social Interactions in Captive Female Rhesus Macaques (Macaca mulatta)

Previous reports suggest that female macaques with greater similarity in emotionality and nervous temperament, as evaluated in a well-established BioBehavioral Assessment (BBA) at the California National Primate Research Center, were more likely to form successful pairs. We tested whether the same measures can also predict the quality of social interactions among 20 female rhesus macaque pairs. We correlated the pairs’ emotionality and nervous temperament scores obtained in infancy and the levels of behaviors recorded systematically during the pairing process years later. Supporting previous findings, partners with similar emotionality scores were more affiliative, and pairs with similar nervous temperament expressed less dominance/submissive behavior. Exploratorily, we found that pairs that were better at processing social information (part of BBA) were also more anxious. Such animals should be prioritized to be introduced in rooms that house calmer, less aggressive animals and provide opportunities for hiding to alleviate their anxiety. Indeed, positive social experiences not only promote animal welfare, but also reduce stress related confounds and unexplained data variability. Therefore, by incorporating the animals’ temperament into the pair configuration process we increase the likelihood of forming high-quality pairs, both in terms of welfare and the research of which they are a part.

Knowledge of Biobehavioral Organization Can Facilitate Better Science: A Review of the BioBehavioral Assessment Program at the California National Primate Research Center

Animals vary on intrinsic characteristics such as temperament and stress responsiveness, and this information can be useful to experimentalists for identifying more homogeneous subsets of animals that show consistency in risk for a particular research outcome. Such information can also be useful for balancing experimental groups, ensuring animals within an experiment have similar characteristics. In this review, we describe the BioBehavioral Assessment Program at the California National Primate Research Center, which, since its inception in 2001, has been providing quantitative information on intrinsic characteristics to scientists for subject selection and balancing, and to colony management staff for management purposes. We describe the program and review studies relating to asthma, autism, behavioral inhibition, etc., where the BBA Program was used to select animals. We also review our work, showing that factors such as rearing, ketamine exposure, and prenatal experience can affect biobehavioral organization in ways that some investigators might want to control for in their studies. Attention to intrinsic characteristics of subject populations is consistent with the growing interest in precision medicine and can lead to a reduction in animal numbers, savings in time and money for investigators, and reduced distress for the animals.

Divergent Enteroviruses from Macaques with Chronic Diarrhea

We report the draft genome sequences of five novel members of the family Picornaviridae that were isolated from the stool of rhesus macaques ( Macaca mulatta ) with chronic diarrhea. The strains were named NOLA-1 through NOLA-5 because the macaques were residents of the Tulane National Primate Research Center.

Neuro-pharmacological reinstatement of ovulation and associated neurobiology in a macaque model of functional hypothalamic amenorrhoea

STUDY QUESTION What is the underlying neuropathology in a cynomolgus macaque model of functional hypothalamic amenorrhoea (FHA) and can it be normalized to restore ovulation? SUMMARY ANSWER Anovulatory monkeys exhibited increased hypothalamic norepinephrine (NE), kisspeptin and gonadotropin-releasing hormone (GnRH) in the early follicular phase, but administration of the NE reuptake inhibitor (NRI), reboxetine (REB), restored ovulation during stress and normalized NE, kisspeptin and GnRH. WHAT IS KNOWN ALREADY Female cynomolgus macaques, like women, show individual reproductive sensitivity to modest psychosocial and metabolic stress. During stress, resilient females ovulate through two menstrual cycles whereas stress-sensitive (SS) macaques immediately cease ovulation. On Day 5 of a non-stressed menstrual cycle, resilient macaques have less NE synthesizing enzyme [dopamine β-hydroxylase (DBH)], kisspeptin and GnRH innervation of the medial basal hypothalamus but more endogenous serotonin than SS macaques. Stress increased DBH/NE, kisspeptin and GnRH but did not alter serotonin. STUDY DESIGN, SIZE, DURATION In a longitudinal design, 27 adult (7–13 years) female cynomolgus macaques (Macaca fascicularis) with three different levels of sensitivity to stress were monitored with daily vaginal swabs and frequent serum progesterone (P) measurements. Three 90-day experimental periods called ‘Cycle Sets’ were monitored. A Cycle Set consisted of one ovulatory menstrual cycle without stress, and two cycles, or 60 days, with modest stress. Each Cycle Set was followed by a rest period. During a Cycle Set, individuals were either untreated (placebo) or administered escitalopram (CIT) or REB. Ultimately, half of each sensitivity group was euthanized during stress with CIT or REB treatment and the hypothalamus was obtained. Neurobiological endpoints were compared between CIT and REB treatment groups in stress resilient and SS monkeys. PARTICIPANTS/MATERIALS, SETTING, METHODS The monkeys were housed at the University of Pittsburgh primate facility for the duration of the experiments. Upon euthanasia, their brains and serum samples were shipped to the Oregon National Primate Research Center. The hypothalamus was examined with immunohistochemistry for the expression of DBH (a marker for NE axons), kisspeptin and GnRH. P was measured in the serum samples by radioimmunoassay. MAIN RESULTS AND THE ROLE OF CHANCE Daily administration of REB restored ovulation in 9 of 10 SS animals during stress. Of note, REB significantly increased P secretion during stress in the most sensitive group (P = 0.032), which indicates ovulation. CIT lacked efficacy. REB significantly reduced DBH/NE, kisspeptin and GnRH axon density in the hypothalamus relative to CIT treatment (P = 0.003. 0.018 and 0.0001, respectively) on Day 5 of the menstrual cycle in resilient and sensitive groups. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION The US FDA has not approved REB for human use, although it is used in Europe for the treatment of depression/anxiety as EdronaxTR. Whether REB could be useful for the treatment of FHA in women has not been determined. WIDER IMPLICATIONS FOR THE FINDINGS The use of an NRI to treat FHA is a novel approach and the potential reinstatement of ovulation could be straightforward compared to current treatment protocols. The underlying neurobiology provides a compelling case for treating the origin of the pathology, i.e. elevated NE, rather than circumventing the hypothalamus altogether with gonadotropins, which have associated risks such as hyperstimulation syndrome or multiple births. STUDY FUNDING/COMPETING INTEREST(S) Portions of this study were supported by NIH grant HD062864 to C.L.B., NIH grant HD62618 to J.L.C. and C.L.B. and 1P51 OD011092 for the operation of the Oregon National Primate Research Center. There were no competing interests.

Urogenital Lesions in Nonhuman Primates at 2 National Primate Research Centers

Given their genetic and anatomic similarities to humans, nonhuman primates (NHPs) may serve as animal models for urogenital diseases of humans. The purpose of this study was to examine the frequency of spontaneous urogenital lesions occurring over a 30-year period at the Yerkes and Southwest National Primate Research Centers and to compare and contrast lesions occurring in Old World versus New World primates. Lesions occurring in the chimpanzee ( Pan troglodytes), baboon ( Papio spp.), rhesus macaque ( Macaca mulatta), cynomolgus macaque ( Macaca fascicularis), pig-tailed macaque ( Macaca nemestrina), sooty mangabey ( Cercocebus atys), common marmoset ( Callithrix jacchus), cotton-top tamarin ( Sanguinus oedipus), and squirrel monkey ( Saimiri sciureus) are discussed. The most common lesions of the kidney were medullary amyloidosis, renal cysts, renal tubular degeneration, glomerulonephritis or glomerulopathy, nephritis, nephrocalcinosis, pyelonephritis, and hydronephrosis. Specific causes of renal tubular disease included pigmentary nephrosis and tubular lipidosis. Renal tumors, including renal adenoma and carcinoma, lymphoma, and nephroblastoma, were infrequent diagnoses in all species. Endometriosis was the most frequently diagnosed lesion of the female genital tract. Of the animals examined in this study, it was most frequent in Old World primates. Leiomyoma was the most common uterine tumor. Granulosa cell tumor was the most frequently observed neoplasm of the ovaries, followed by teratoma. Of animals included in the study, most ovarian tumors occurred in baboons. Neoplasms of the male reproductive tract included interstitial cell tumor, seminoma, penile squamous cell carcinoma, penile papilloma, and histiocytoma. In New World monkeys, renal lesions were reported more frequently than genital lesions.

Discovery of a novel simian pegivirus in common marmosets (Callithrix jacchus) with lymphocytic enterocolitis

From 2010 to 2015, 73 common marmosets (Callithrix jacchus) housed at the Wisconsin National Primate Research Center (WNPRC) were diagnosed postmortem with lymphocytic enterocolitis. We used unbiased deep-sequencing to screen the blood of deceased enterocolitis-positive marmosets for the presence of RNA viruses. In five out of eight marmosets with lymphocytic enterocolitis, we discovered a novel pegivirus that was not present in ten subsequently deep-sequenced matched, clinically-normal common marmosets with no evidence of lymphocytic enterocolitis. The novel virus, which we have named Southwest bike trail virus (SOBV), is most closely related (68% nucleotide identity) to a strain of simian pegivirus A that was previously isolated from a three-striped night monkey (Aotus trivirgatus). To determine the prevalence of this novel virus within the WNPRC marmoset colony, we screened 146 living animals and found an overall prevalence of 34% (50/146). Over the next four years, 85 of the 146 screened marmosets died or were euthanized and were examined histologically for lymphocytic enterocolitis. Out of these 85 animals, 27 SOBV-positive common marmosets had developed lymphocytic enterocolitis, compared to 42 SOBV-negative common marmosets, indicating no evidence of an association between this virus and development of enterocolitis in this cohort (p=0.0798). The novel pegivirus was also found in two of 32 (6%) clinically-normal common marmosets screened while in quarantine during the transfer from the New England Primate Research Center to the WNPRC, suggesting SOBV has different prevalence at different centers and could exert confounding influences on the comparison of marmoset studies from multiple centers.ImportanceCommon marmosets (Callithrix jacchus) are a valuable model species. We discovered two variants of a novel simian pegivirus, which we named the Southwest bike trail virus (SOBV), in common marmosets which had postmortem histologic diagnosis of lymphocytic enterocolitis. The virus was not present in ten matched, clinically-normal controls. We screened 146 live healthy common marmosets in the Wisconsin National Primate Research Center colony and found 34% (50/146) of the animals were SOBV-positive. SOBV was also present in two of 32 (6%) clinically-normal common marmosets from the New England Primate Research Center. These findings could have confounding effects in animal studies, especially those in which infection-free animals are desired, and they demonstrate the need for further investigations into SOBV transmission, the length of time of SOBV persistence, and SOBV prevalence at other primate centers, in order to increase understanding of the effects of SOBV and of this viral genus.

High Diversity and Novel Enteric Viruses in Fecal Viromes of Healthy Wild and Captive Thai Cynomolgus Macaques (Macaca fascicularis)

Cynomolgus macaques are common across South East Asian countries including Thailand. The National Primate Research Center of Thailand, Chulalongkorn University (NPRCT-CU) captures wild-borne cynomolgus macaque for research use. Limited information is available on the enteric viruses and possible zoonotic infections into or from cynomolgus macaques. We characterized and compare the fecal virome of two populations; healthy wild-originated captive cynomolgus macaques (n = 43) reared in NPRCT-CU and healthy wild cynomolgus macaques (n = 35). Over 90% of recognized viral sequence reads amplified from feces were from bacterial viruses. Viruses from seven families of mammalian viruses were also detected (Parvoviridae, Anelloviridae, Picornaviridae, Adenoviridae, Papillomaviridae, Herpesviridae, and Caliciviridae). The genomes of a member of a new picornavirus genus we named Mafapivirus, a primate chapparvovirus, and a circular Rep-encoding single-strand (CRESS) DNA virus were also characterized. Higher abundance of CRESS DNA viruses of unknown tropism and invertebrate-tropic ambidensovirus were detected in wild versus captive macaques likely reflecting dietary differences. Short term rearing in captivity did not have a pronounced effect on the diversity of mammalian viruses of wild cynomolgus macaques. This study is the first report of the fecal virome of cynomolgus macaques, non-human primates frequently used in biomedical research and vaccination studies.