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Left ventricular noncompaction (LVNC) involving genetic mutation is categorized as an unclassified cardiomyopathy, and its diagnostic criteria have not been standardized. This could be because precise animal models of LVNC have not been created in any laboratory animal species. This study aimed to analyze the pathophysiology and familial tendency of LVNC in Japanese macaques. Two Japanese macaques with LVNC, and their parents who were suspected of having cardiac disease, were examined. One macaque with LVNC was examined using chest radiography, echocardiography, cardiac biomarkers, cardiac MRI, and pathologic examination, and the other macaque was examined using chest radiography, echocardiography, and cardiac biomarkers. Their common father and the mother of one of the macaques with LVNC were tested for chest radiography and cardiac biomarkers. Echocardiography revealed a meshwork with trabeculation and deep intertrabecular recesses in all their left ventricular walls. The 2 macaques with LVNC demonstrated a layered appearance of the myocardium, consisting of noncompacted myocardium on the endocardial side and compacted myocardium on the epicardial side, with a noncompacted/compacted ratio of 6.0 and 5.8, respectively. One of the 2 macaques with LVNC (case 1) had elevated levels of troponin I, troponin T, atrial natriuretic peptide, and brain natriuretic peptide. The second macaque with LVNC (case 2) showed blood flow in the intertrabecular recesses on echocardiography. The common father (case 3) of the 2 macaques with LVNC and the mother (case 4) of one of the macaques with LVNC had elevated levels of troponin I and troponin T. In case 1, histopathologic examination revealed fibrous thickening of the endocardium, fibrosis of the myocardial interstitium, myocardial disarray, vacuolar degeneration, anisonucleosis, and necrosis of myocardial cells. This suggests that Japanese macaques could serve as a reliable animal model of human LVNC.

Human fetuses at term are large relative to the dimensions of the maternal birth canal, implying that their birth can be associated with difficulties. The tight passage through the human birth canal can lead to devastating outcomes if birth becomes obstructed, including maternal and fetal death. Although macaques have to accommodate similarly large fetuses, relative to their maternal birth canals, it was not known whether macaque mothers face birth difficulties similar to humans. Based on 27 y of demographic data from a semi-free-ranging, closely monitored population of Japanese macaques ( Macaca fuscata ), we found no birth-associated mortality in macaques. This differs from the situation in many human populations. We suggest three nonmutually exclusive hypotheses to explain these observations. i) The macaque fetal skull is similarly flexible as the human fetal skull. ii) The macaque pelvis and connective tissue show greater flexibility during birth. iii) The interplay between macaque pelvic shape and birth dynamics is smoother and incurs fewer complications than in humans., Competing Interests: Competing interests statement:The authors declare no competing interest.

Coronavirus disease 2019 (COVID-19) reportedly affects male reproductive function by causing spermatogenesis dysfunction and suppressing testosterone secretion. However, the relationship between COVID-19 and impaired reproductive function, such as whether these effects on reproductive function are a direct effect of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection in male reproductive organs or an indirect effect of high fever, is not known. Here, we examined whether the cell entry molecules of SARS-CoV-2, namely, ACE2, NRP1, TMPRSS2, and FURIN, are expressed in the male reproductive organs using the testes and accessory gonads of macaques during the breeding season. RT-PCR expression analysis showed that the testes alone expressed all four molecules. Immunohistochemical staining of testis tissue sections revealed that ACE2 is expressed in Leydig cells and the apical region of Sertoli cells, whereas NRP1 is expressed in the cell bodies surrounding the Leydig and Sertoli cell nuclei. FURIN is mainly expressed in Leydig cells, secondary spermatocytes, and spermatids. However, TMPRSS2 immunopositive cells were not observed. Therefore, it was not possible to observe cells expressing all four molecules in the gonads and accessory gonads of male primates. These results suggest that SARS-CoV-2 is unlikely to directly affect spermatogenesis in primates or proliferate in cells of the seminiferous tubules and undergo release into the semen through the previously known ACE2-mediated infection route. However, the expression of three molecules, including ACE2, was observed in Leydig cells, suggesting that testosterone synthesis and secretion may be affected when primates, including humans, are infected with SARS-CoV-2., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Systemic amyloid light-chain (AL) amyloidosis is an infrequent disease in which amyloid fibrils derived from the immunoglobulin light chain are deposited in systemic organs, resulting in functional impairment. This disease has been notably uncommon in animals, and nonhuman primates have not been reported to develop it. In this study, we identified the systemic AL kappa chain amyloidosis in a captive Bornean orangutan (Pongo pygmaeus) and analyzed its pathogenesis. Amyloid deposits were found severely in the submucosa of the large intestine, lung, mandibular lymph nodes, and mediastinal lymph nodes, with milder lesions in the liver and kidney. Mass spectrometry-based proteomic analysis revealed an abundant constant domain of the immunoglobulin kappa chain in the amyloid deposits. Immunohistochemistry further confirmed that the amyloid deposits were positive for immunoglobulin kappa chains. In this animal, AL amyloidosis resulted in severe involvement of the gastrointestinal submucosa and lymph nodes, which is consistent with the characteristics of AL amyloidosis in humans, suggesting that AL amyloid may have a similar deposition mechanism across species. This report enhances the pathological understanding of systemic AL amyloidosis in animals by providing a detailed characterization of this disease based on proteomic analysis., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Facial expressions have increasingly been used to assess emotional states in mammals. The recognition of pain in research animals is essential for their well-being and leads to more reliable research outcomes. Automating this process could contribute to early pain diagnosis and treatment. Artificial neural networks have become a popular option for image classification tasks in recent years due to the development of deep learning. In this study, we investigated the ability of a deep learning model to detect pain in Japanese macaques based on their facial expression. Thirty to 60 min of video footage from Japanese macaques undergoing laparotomy was used in the study. Macaques were recorded undisturbed in their cages before surgery (No Pain) and one day after the surgery before scheduled analgesia (Pain). Videos were processed for facial detection and image extraction with the algorithms RetinaFace (adding a bounding box around the face for image extraction) or Mask R-CNN (contouring the face for extraction). ResNet50 used 75% of the images to train systems; the other 25% were used for testing. Test accuracy varied from 48 to 54% after box extraction. The low accuracy of classification after box extraction was likely due to the incorporation of features that were not relevant for pain (for example, background, illumination, skin color, or objects in the enclosure). However, using contour extraction, preprocessing the images, and fine-tuning, the network resulted in 64% appropriate generalization. These results suggest that Mask R-CNN can be used for facial feature extractions and that the performance of the classifying model is relatively accurate for nonannotated single-frame images.

Chimpanzees ( Pan troglodytes ) with teeth severely damaged by dental caries and/or periodontal disease are often managed with medication and/or tooth extraction. A common endodontic treatment for severely decayed teeth in a 26-year-old female chimpanzee is reported. The left maxillary central incisor tooth had lost its crown, probably due to trauma that was not recent, and it had a fistula most likely due to chronic apical periodontitis. The diagnosis was confirmed radiographically before treatment. To treat the infected root canal, endodontic treatment used in humans was adapted for a chimpanzee. After the treatment, the tooth was sealed using an adhesive resin composite. At 11-years post-treatment, there were no signs of recurrence of the lesion or of failure of the tooth seal. The results of this case report suggest that common endodontic treatments used in humans are also effective in chimpanzees., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Previous studies suggest that housing relocation may be stressful for captive non-human primates. Our study investigated the stress levels of Japanese macaques during a housing relocation by measuring their daily fecal cortisol metabolites, which are often used as an indicator of stress., Methods: Ten adult Japanese macaques, single-housed for research purposes, were relocated to a new facility. Fecal samples were collected daily for 7 days. Cortisol metabolite concentrations were determined via enzyme immunoassay., Results: No significant differences in cortisol metabolite levels were found in 7 days, but concentration levels showed that the highest median was associated to the relocation day., Conclusions: The minimal cortisol metabolite increase suggests that there was a slight activity increase in the hypothalamic-pituitary-adrenal axis. Techniques encouraging cooperation of the monkeys, the short time duration of the relocation, and consistency in the environment may have contributed to the minimal stress levels observed., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A tetanus outbreak occurred during 2014-2015 in the rhesus macaques reared in an open enclosure in our facility. As the soil of the facility was suspected to be contaminated with Clostridium tetani spores, there was a risk of further tetanus occurring among the macaques. To protect them from tetanus, a tetanus toxoid vaccination was recommended; however, the vaccinated elderly animals might not be effectively protected due to insufficient humoral immune responses. Hence, we evaluated the dynamics of antibody responses among rhesus macaques of all age groups vaccinated with two-dose tetanus toxoid at a 1-year interval during a 3-year follow-up study. The vaccination developed anti-tetanus toxin-specific antibodies in animals of all age groups, the antibody levels peaked 1 year after the second vaccination, and the peak levels decreased with age. However, the levels among elderly individuals (aged ≥13 years) were still higher than the threshold level, which was supposed to protect them from tetanus development. Although the rhesus macaques in our facility had a risk of occasional exposure to the spores due to the outbreak, no incidence of tetanus has ever occurred to date. These results indicate that the vaccination protocol is effective in protecting not only younger but also older animals from tetanus.

A comparison of neuroanatomical features of the brain between humans and our evolutionary relatives, nonhuman primates, is key to understanding the human brain system and the neural basis of mental and neurological disorders. Although most comparative MRI studies of human and nonhuman primate brains have been based on brains of primates that had been used as subjects in experiments, it is essential to investigate various species of nonhuman primates in order to elucidate and interpret the diversity of neuroanatomy features among humans and nonhuman primates. To develop a research platform for this purpose, it is necessary to harmonize the scientific contributions of studies with the standards of animal ethics, animal welfare, and the conservation of brain information for long-term continuation of the field. In previous research, we first developed a gated data-repository of anatomical images obtained using 9.4-T ex vivo MRI of postmortem brain samples from 12 nonhuman primate species, and which are stored at the Japan Monkey Centre. In the present study, as a second phase, we released a collection of T2-weighted images and diffusion tensor images obtained in nine species: white-throated capuchin, Bolivian squirrel monkey, stump-tailed macaque, Tibet monkey, Sykes' monkey, Assamese macaque, pig-tailed macaque, crested macaque, and chimpanzee. Our image repository should facilitate scientific discoveries in the field of comparative neuroscience. This repository can also promote animal ethics and animal welfare in experiments with nonhuman primate models by optimizing methods for in vivo and ex vivo MRI scanning of brains and supporting veterinary neuroradiological education. In addition, the repository is expected to contribute to conservation, preserving information about the brains of various primates, including endangered species, in a permanent digital form., Competing Interests: Declaration of Competing Interest The authors have no affiliation with any organization with a direct or indirectfinancial interest in the subject matter discussed in the manuscript., (Copyright © 2023. Published by Elsevier Inc.)

Common marmosets are promising laboratory animals for the study of higher brain functions. Although there are many opportunities to use sedatives and anesthetics in resting brain function measurements in marmosets, their effects on the resting-state network remain unclear. In this study, the effects of sedatives or anesthetics such as midazolam, dexmedetomidine, co-administration of isoflurane and dexmedetomidine, propofol, alfaxalone, isoflurane, and sevoflurane on the resting brain function in common marmosets were evaluated using independent component analysis, dual regression analysis, and graph-theoretic analysis; and the sedatives or anesthetics suitable for the evaluation of resting brain function were investigated. The results show that network preservation tendency under light sedative with midazolam and dexmedetomidine is similar regardless of the type of target receptor. Moreover, alfaxalone, isoflurane, and sevoflurane have similar effects on resting state brain function, but only propofol exhibits different tendencies, as resting brain function is more preserved than it is following the administration of the other anesthetics. Co-administration of isoflurane and dexmedetomidine shows middle effect between sedatives and anesthetics., (© The Author(s) 2022. Published by Oxford University Press.)

A- and B-antigens are present on red blood cells (RBCs) as well as other cells and secretions in Hominoidea including humans and apes such as chimpanzees and gibbons, whereas expression of these antigens on RBCs is subtle in monkeys such as Japanese macaques. Previous studies have indicated that H-antigen expression has not completely developed on RBCs in monkeys. Such antigen expression requires the presence of H-antigen and A- or B-transferase expression in cells of erythroid lineage, although whether or not ABO gene regulation is associated with the difference of A- or B-antigen expression between Hominoidea and monkeys has not been examined. Since it has been suggested that ABO expression on human erythrocytes is dependent upon an erythroid cell-specific regulatory region or the + 5.8-kb site in intron 1, we compared the sequences of ABO intron 1 among non-human primates, and demonstrated the presence of sites orthologous to the + 5.8-kb site in chimpanzees and gibbons, and their absence in Japanese macaques. In addition, luciferase assays revealed that the former orthologues enhanced promoter activity, whereas the corresponding site in the latter did not. These results suggested that the A- or B-antigens on RBCs might be ascribed to emergence of the + 5.8-kb site or the corresponding regions in ABO through genetic evolution., (© 2023. The Author(s).)

Background: Although some studies have reported cardiac diseases in macaques, an adequate screening method for cardiac enlargement has not yet been established. This study aimed to evaluate the positioning of macaques for radiographs and establish reference intervals for the cardiothoracic ratio (CTR)., Materials and Methods: We developed a device for chest radiography in the sitting position and performed chest radiography in 50 Japanese and 48 rhesus macaques to evaluate the CTR and chest cavity size., Results: In Japanese and rhesus macaques, the thorax height was significantly larger, the heart width was significantly smaller, and the mean CTR was significantly smaller in the sitting position than in the prone position. The reference intervals for CTR in the sitting position were 51.6 ± 4.6% and 52.2 ± 5.1% in Japanese and rhesus macaques, respectively., Conclusion: Thoracic radiographic images obtained in a sitting position resulted in a smaller CTR and a larger thorax height, which could be useful for detecting pulmonary and cardiac abnormalities., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Changes in facial expression provide cues for assessing emotional states in mammals and may provide non-verbal signals of pain. This study uses geometric morphometrics (GMM) to explore the facial shape variation in female Japanese macaques who underwent experimental laparotomy. Face image samples were collected from video footage of fourteen macaques before surgery and 1, 3, and 7 days after the procedure. Image samples in the pre-surgical condition were considered pain-free, and facial expressions emerging after surgery were investigated as potential indicators of pain. Landmarks for shape analysis were selected based on the underlying facial musculature and their corresponding facial action units and then annotated in 324 pre-surgical and 750 post-surgical images. The expression of pain is likely to vary between individuals. Tightly closed eyelids or squeezed eyes and lip tension were the most commonly observed facial changes on day 1 after surgery (p < 0.01974). A good overall inter-rater reliability [ICC = 0.99 (95% CI 0.75-1.0)] was observed with the method. The study emphasizes the importance of individualized assessment and provides a better understanding of facial cues to pain for captive macaque care., (© 2022. The Author(s).)

Facial expressions are subtle cues, central for communication and conveying emotions in mammals. Traditionally, facial expressions have been classified as a whole (e.g. happy, angry, bared-teeth), due to automatic face processing in the human brain, i.e., humans categorise emotions globally, but are not aware of subtle or isolated cues such as an eyebrow raise. Moreover, the same facial configuration (e.g. lip corners pulled backwards exposing teeth) can convey widely different information depending on the species (e.g. humans: happiness; chimpanzees: fear). The Facial Action Coding System (FACS) is considered the gold standard for investigating human facial behaviour and avoids subjective interpretations of meaning by objectively measuring independent movements linked to facial muscles, called Action Units (AUs). Following a similar methodology, we developed the CalliFACS for the common marmoset. First, we determined the facial muscular plan of the common marmoset by examining dissections from the literature. Second, we recorded common marmosets in a variety of contexts (e.g. grooming, feeding, play, human interaction, veterinary procedures), and selected clips from online databases (e.g. YouTube) to identify their facial movements. Individual facial movements were classified according to appearance changes produced by the corresponding underlying musculature. A diverse repertoire of 33 facial movements was identified in the common marmoset (15 Action Units, 15 Action Descriptors and 3 Ear Action Descriptors). Although we observed a reduced range of facial movement when compared to the HumanFACS, the common marmoset's range of facial movements was larger than predicted according to their socio-ecology and facial morphology, which indicates their importance for social interactions. CalliFACS is a scientific tool to measure facial movements, and thus, allows us to better understand the common marmoset's expressions and communication. As common marmosets have become increasingly popular laboratory animal models, from neuroscience to cognition, CalliFACS can be used as an important tool to evaluate their welfare, particularly in captivity., Competing Interests: The authors have declared that no competing interests exist.

One of the current threats to the bonobo (Pan paniscus), a highly endangered ape species only found in the Democratic Republic of the Congo, are anthropozoonoses caused by human respiratory viruses. To date, epidemiological information regarding respiratory viral infections in bonobos is limited. In this study, we examined fecal immunoglobulin A antibodies against human respiratory viruses in bonobos, which may help estimating the viral prevalence. A substantial proportion of bonobos were positive for the antiviral antibodies, including those against parainfluenza virus, respiratory syncytial virus, influenza virus, rhinovirus, and mumps virus. The prevalence of the antibodies was found to depend on the viral species and bonobo populations, suggesting that the bonobos had been exposed to these respiratory viruses. These results may indicate the need for an epidemiological evidence-based action plan for the protection of bonobos from anthropozoonoses., (© 2021. Japan Monkey Centre.)

Background: Assessment of pain in macaques is challenging. The aims of this study were (1) to investigate current knowledge and attitudes of primate veterinarians concerning acute pain in macaques; (2) to synthesise current knowledge and opinion to facilitate pain assessment. A primary question of interest was whether more confident individuals differ in their knowledge and attitudes from less-confident individuals., Methods: An online survey was conducted amongst primate veterinarians serving both laboratories and zoos/sanctuaries. The questionnaire consisted of demographic information, attitudes towards pain, pain rating and analgesics, pain recognition and confidence in recognising pain and sources of information used., Results and Conclusions: There was generally good use of analgesia by respondents. More confident individuals reported that they recognise pain both behaviourally and in facial expressions, rated all pain signs more highly and used more analgesics. Specialist support networks aimed at increasing veterinarian confidence in macaque pain assessment could be beneficial., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mammalian faeces can be collected noninvasively during field research and provide valuable information on the ecology and evolution of the source individuals. Undigested food remains, genome/metagenome, steroid hormones, and stable isotopes obtained from faecal samples provide evidence on diet, host/symbiont genetics, and physiological status of the individuals. However, proteins in mammalian faeces have hardly been studied, which hinders the molecular investigations into the behaviour and physiology of the source individuals. Here, we apply mass spectrometry-based proteomics to faecal samples (n = 10), collected from infant, juvenile, and adult captive Japanese macaques (Macaca fuscata), to describe the proteomes of the source individual, of the food it consumed, and its intestinal microbes. The results show that faecal proteomics is a useful method to: (i) investigate dietary changes along with breastfeeding and weaning, (ii) reveal the taxonomic and histological origin of the food items consumed, and (iii) estimate physiological status inside intestinal tracts. These types of insights are difficult or impossible to obtain through other molecular approaches. Most mammalian species are facing extinction risk and there is an urgent need to obtain knowledge on their ecology and evolution for better conservation strategy. The faecal proteomics framework we present here is easily applicable to wild settings and other mammalian species, and provides direct evidence of their behaviour and physiology., (© 2021 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd.)

Captive primates require environmental enrichment to minimize physical and mental stress. However, only a few objective evaluations have been performed to assess environment-induced physiological variations in these animals. In this study, we evaluated the usage of the metabolic profile test (MPT) to assess the influences of the housing environment on the physiology of Japanese macaques. Five male macaques were housed in an old type of cage (old cage group), in which the macaques were exposed to wind (except for a shelter box), and four males were in a new -type of cage (new cage group), which had a sub-room with a waterer that was surrounded by insulating panels. Blood samples were collected bimonthly for a year from the two groups to determine the complete blood count and blood biochemistry. The increase in the body weight of the macaques in both groups was suppressed during the cold season. Furthermore, this suppression was more pronounced in the old cage group, suggesting that the energy expenditure was higher in the old cage group than in the new cage group. Moreover, the red blood cell count and hematocrit values were higher during the cold season in both cages than during the warm season, suggesting that macaques were dehydrated during the cold season. Dehydration tendency was more pronounced in the macaques from the old cage group than in those from the new cage group, suggesting that their water intake decreased during the cold season. Our results suggest that the MPT can be used to evaluate environment-induced physiological variations in Japanese macaques.

Facial expressions are complex and subtle signals, central for communication and emotion in social mammals. Traditionally, facial expressions have been classified as a whole, disregarding small but relevant differences in displays. Even with the same morphological configuration different information can be conveyed depending on the species. Due to a hardwired processing of faces in the human brain, humans are quick to attribute emotion, but have difficulty in registering facial movement units. The well-known human FACS (Facial Action Coding System) is the gold standard for objectively measuring facial expressions, and can be adapted through anatomical investigation and functional homologies for cross-species systematic comparisons. Here we aimed at developing a FACS for Japanese macaques, following established FACS methodology: first, we considered the species' muscular facial plan; second, we ascertained functional homologies with other primate species; and finally, we categorised each independent facial movement into Action Units (AUs). Due to similarities in the rhesus and Japanese macaques' facial musculature, the MaqFACS (previously developed for rhesus macaques) was used as a basis to extend the FACS tool to Japanese macaques, while highlighting the morphological and appearance changes differences between the two species. We documented 19 AUs, 15 Action Descriptors (ADs) and 3 Ear Action Units (EAUs) in Japanese macaques, with all movements of MaqFACS found in Japanese macaques. New movements were also observed, indicating a slightly larger repertoire than in rhesus or Barbary macaques. Our work reported here of the MaqFACS extension for Japanese macaques, when used together with the MaqFACS, comprises a valuable objective tool for the systematic and standardised analysis of facial expressions in Japanese macaques. The MaqFACS extension for Japanese macaques will now allow the investigation of the evolution of communication and emotion in primates, as well as contribute to improving the welfare of individuals, particularly in captivity and laboratory settings., Competing Interests: The authors have declared that no competing interests exist.

The objectives of this study were (a) to establish a population pharmacokinetic model and (b) to investigate the clinical and physiological effects of a single bolus dose of propofol in common marmosets. In Study 1, pharmacokinetic analysis was performed in six marmosets under sevoflurane anaesthesia. 8 mg/kg of propofol was administrated at a rate of 4 mg kg -1  min -1 . Blood samples were collected 2, 5, 15, 30, 60, 90, 120 or 180 min after starting propofol administration. Plasma concentration was measured, and population pharmacokinetic modelling was performed. A two-compartment model was selected as the final model. The population pharmacokinetic parameters were as follows: V 1  = 1.14 L, V 2  = 77.6 L, CL 1  = 0.00182 L/min, CL 2  = 0.0461 L/min. In Study 2, clinical and physiological parameters were assessed and recorded every 2 min after 12 mg/kg of propofol was administrated at a rate of 4 mg kg -1  min -1 . Immobilization was sustained for 5 min following propofol administration without apparent bradycardia. While combination of propofol and sevoflurane caused apnoea in Study 1, apnoea was not observed following single administration of propofol in Study 2. These data provide bases for further investigation on intravenous anaesthesia using propofol in common marmosets., (© 2020 John Wiley & Sons Ltd.)

Background: Anaesthesia is often required in common marmosets undergoing various procedures. The aim of this study was to evaluate anaesthetic and cardiopulmonary effects of alfaxalone, alfaxalone-ketamine and alfaxalone-butorphanol-medetomidine in common marmosets., Methods: The following treatments were repeatedly administered to seven female common marmosets: Treatment A, alfaxalone (12 mg kg -1 ) alone; treatment AK, alfaxalone (1 mg animal -1 ) plus ketamine (2.5 mg animal -1 ); treatment AMB, alfaxalone (4 mg kg -1 ), medetomidine (50 µg kg -1 ) plus butorphanol (0.3 mg kg -1 ); and treatment AMB-Ati, AMB with atipamezole at 45 minutes., Results and Conclusions: Marmosets became laterally recumbent and unresponsive for approximately 30 minutes in A and AK and for approximately 60 minutes in AMB. The animals showed rapid recovery following atipamezole injection in AMB-Ati. The decrease in heart rate and SpO 2 was significantly greater in AMB compared to A and AK. Oxygen supplementation, anaesthetic monitors and atipamezole should be available especially when AMB is administered., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Marmoset wasting syndrome (MWS) is clinically characterized by progressive weight loss. Although morbidity and mortality of MWS are relatively high in captive marmosets, its causes remain unknown. Lipid mediators are bioactive metabolites which are produced from polyunsaturated fatty acids, such as arachidonic acid (AA) and eicosapentaenoic acid. These lipid metabolites regulate a wide range of inflammatory responses and they are excreted into the urine. As urinary lipid profiles reflect systemic inflammatory conditions, we comprehensively measured the levels of 141 types of lipid metabolites in the urines obtained from healthy common marmoset (Callithrix jacchus) (N = 7) or marmosets with MWS (N = 7). We found that 41 types of metabolites were detected in all urine samples of both groups. Among them, AA-derived metabolites accounted for 63% (26/41 types) of all detected metabolites. Notably, the levels of AA-derived prostaglandin (PG) E2, PGF2α, thromboxane (TX) B2 and F2-isoprostanes significantly increased in the urine samples of marmosets with MWS. In this study, we found some urinary lipid metabolites which may be involved in the development of MWS. Although the cause of MWS remains unclear, our findings may provide some insight into understanding the mechanisms of development of MWS., Competing Interests: The authors have declared that no competing interests exist.

Background: Biological information about captive Japanese macaques, including hematology and blood chemistry, is still lacking despite the fact that ethological and ecological data have accumulated during decades of field research., Methods: Hematological (511 examinations of 280 Japanese macaques) and blood chemistry data (between 33 and 284 examinations from between 29 and 257 individual macaques) in clinically healthy, simian retrovirus-free Japanese macaques tested between 2009 and 2013 were reviewed., Results and Conclusions: Specific hematological and blood chemistry data for Japanese macaques without clinical signs of disease were provided in this study. Averages presented can be used as hematological parameters for Japanese macaques. Some differences between Japanese macaques and other closely related macaque species were found. Some parameters varied according to macaque age and sex, as well as regional origin. The data in this study will provide useful clinical indices for Japanese macaques in captive and similar conditions., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Helicobacter pylori cagA-positive strains are critically involved in the development of gastric cancer. Upon delivery into gastric epithelial cells via type IV secretion, the cagA-encoded CagA interacts with and thereby perturbs the pro-oncogenic phosphatase SHP2 and the polarity-regulating kinase PAR1b via the tyrosine-phosphorylated EPIYA-C/D segment and the CM sequence, respectively. Importantly, sequences spanning these binding regions exhibit variations among CagA proteins, which influence the pathobiological/oncogenic potential of individual CagA. Here we isolated an H. pylori strain (Hp&#95;TH2099) naturally infecting the stomach of a housed macaque, indicating a zoonotic feature of H. pylori infection. Whole genome sequence analysis revealed that Hp&#95;TH2099 belongs to the hpAsia2 cluster and possesses ABC-type Western CagA, which contains hitherto unreported variations in both EPIYA-C and CM sequences. The CM variations almost totally abolished PAR1b binding. Whereas pTyr + 5 variation in the EPIYA-C segment potentiated SHP2-binding affinity, pTyr-2 variation dampened CagA tyrosine phosphorylation and thus impeded CagA-SHP2 complex formation. As opposed to the H. pylori standard strain, infection of mouse ES cell-derived gastric organoids with Hp&#95;TH2099 failed to elicit CagA-dependent epithelial destruction. Thus, the macaque-isolated H. pylori showed low virulence due to attenuated CagA activity through multiple substitutions in the sequences involved in binding with SHP2 and PAR1b.

How brains develop during early life is one of the most important topics in neuroscience because it underpins the neuronal functions that mature during this period. A comparison of the neurodevelopmental patterns among humans and nonhuman primates is essential to infer evolutional changes in neuroanatomy that account for higher-order brain functions, especially those specific to humans. The corpus callosum (CC) is the major white matter bundle that connects the cerebral hemispheres, and therefore, relates to a wide variety of neuronal functions. In humans, the CC area rapidly expands during infancy, followed by relatively slow changes. In chimpanzees, based on a cross-sectional study, slow changes in the CC area during the juvenile stage and later have also been reported. However, little is known about the developmental changes during infancy. A longitudinal study is also required to validate the previous cross-sectional observations about the chimpanzee CC. The present longitudinal study of magnetic resonance imaging scans demonstrates that the CC development in chimpanzees and humans is characterized by a rapid increase during infancy, followed by gradual increase during the juvenile stage. Several differences between the two species were also identified. First, there was a tendency toward a greater increase in the CC areas during infancy in humans. Second, there was a tendency toward a greater increase in the rostrum during the juvenile stage in chimpanzees. The rostral body is known to carry fibers between the bilateral prefrontal and premotor cortices, and is involved in behavior planning and control, verbal working memory, and number conception. The rostrum is known to carry fibers between the prefrontal cortices, and is involved in attention control. The interspecies differences in the developmental trajectories of the rostral body and the rostrum might be related to evolutional changes in the brain systems.

Objective: To explore the major risk factors linking preoperative characteristics and anaesthesia-related death in dogs in referral hospitals in Japan., Study Design: Observational cohort study., Animals: From April 1, 2010 to March 31, 2011, 4323 dogs anaesthetized in 18 referral hospitals in Japan., Methods: Questionnaire forms were collated anonymously. Death occurring within 48 hours after extubation was considered as an anaesthesia-related death. Patient outcome (alive or dead) was set as the outcome variable. Preoperative general physical characteristics, complete blood cell counts, serum biochemical examinations and intraoperative complications were set as explanatory variables. The risk factors for anaesthesia-related death were evaluated using chi-square test or Fisher's exact test, followed by multivariable logistic regression analysis of the data. Significance was set at p < 0.05., Results: Thirteen dogs that died from surgical error or euthanasia were excluded from statistical analysis. The total mortality rate in this study was 0.65% [28/4310 dogs; 95% confidence interval (CI), 0.41-0.89]. Furthermore, 75% (95% CI, 55.1-89.3) of anaesthesia-related deaths occurred in dogs with pre-existing diseases. Most of the deaths occurred postoperatively (23/28; 82.1%; 95% CI, 63.1-93.9). Preoperative serum glucose concentration <77 mg dL -1 (6/46; 13.0%; 95% CI, 4.9-26.3), disturbance of consciousness (6/50; 12.0%; 95% CI, 4.5-24.3), white cell count >15,200 μL -1 (16/499; 3.4%; 95% CI, 1.9-5.5) and American Society of Anesthesiologists grade III-V (19/1092; 1.7%; 95% CI, 1.1-2.7) were identified as risk factors for anaesthesia-related death. Intraoperative hypoxaemia (8/34; 23.5%; 95% CI, 10.7-41.2) and tachycardia (4/148; 2.7%; 95% CI, 0.7-6.8) were also risk factors for anaesthesia-related death., Conclusions and Clinical Relevance: The results revealed that certain preoperative characteristics were associated with increased odds of anaesthesia-related death, specifically low serum glucose concentration and disturbances of consciousness. Greater attention to correcting preanaesthetic patient abnormalities may reduce the risk of anaesthesia-related death., (Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Rationale: Estimation of the stable isotopic offsets between tissue and diet is important for dietary reconstructions. Although stable isotopic studies of chimpanzees (Pan troglodytes) are increasing, the isotopic offsets in chimpanzees have never been studied. In this study, the carbon and nitrogen stable isotopic offset values in hair and feces were measured for 13 captive chimpanzees for the first time., Methods: All consumed food items and quantities were recorded for each individual for 1 week. Food samples were typically collected three times, hair was collected 3 weeks after the experimental week, and feces were collected ad libitum during the experimental week. The stable carbon and nitrogen isotope ratios were measured using elemental analyzer-isotope ratio mass spectrometry (EA-IRMS)., Results: As the results of Monte Carlo analysis, the estimated carbon and nitrogen offsets between the hair and diet were +3.0 to +3.9‰ and +2.8 to +3.7‰, respectively, for the 95% confidence intervals (CIs). The 95% CIs of the carbon and nitrogen offset values between the feces and diet were -1.6 to 0.0‰ and +1.2 to +2.7‰, respectively., Conclusions: These offset values are generally consistent with those of the other primate species reported in previous studies. However, potential variations in the offset values due to dietary and physiological factors should be studied in detail in the future. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Streptococcus troglodytae TKU31 was isolated from the oral cavity of a chimpanzee (Pan troglodytes) and was found to be the most closely related species of the mutans group streptococci to Streptococcus mutans. The complete sequence of TKU31 genome consists of a single circular chromosome that is 2,097,874 base pairs long and has a G + C content of 37.18%. It possesses 2082 coding sequences (CDSs), 65 tRNAs and five rRNA operons (15 rRNAs). Two clustered regularly interspaced short palindromic repeats, six insertion sequences and two predicted prophage elements were identified. The genome of TKU31 harbors some putative virulence associated genes, including gtfB, gtfC and gtfD genes encoding glucosyltransferase and gbpA, gbpB, gbpC and gbpD genes encoding glucan-binding cell wall-anchored protein. The deduced amino acid identity of the rhamnose-glucose polysaccharide F gene (rgpF), which is one of the serotype determinants, is 91% identical with that of S. mutans LJ23 (serotype k) strain. However, two other virulence-associated genes cnm and cbm, which encode the collagen-binding proteins, were not found in the TKU31 genome. The complete genome sequence of S. troglodytae TKU31 has been deposited at DDBJ/European Nucleotide Archive/GenBank under the accession no. AP014612., (© 2016 The Societies and John Wiley & Sons Australia, Ltd.)

Lymphocryptovirus (LCV) is one of the major gena in the herpesvirus family and is widely disseminated among primates. LCVs of human and rhesus macaques are shown to be causative agents of a number of malignant diseases including lymphoma and carcinoma. Bonobos (Pan paniscus) are highly endangered and the least studied species of the great apes. Considering the potential pathogenicity of the LCV that might threaten the fate of wild bonobos, population-based epidemiological information in terms of LCV prevalence in different location of Bonobo's habitats will help propose improved conservation strategies for the bonobos. However, such data are not available yet because it is very difficult to collect blood samples in the wild and thus virtually impossible to conduct sero-epidemiological study on the wild ape. In order to overcome this issue, we focused on evaluating anti-LCV IgA in the feces of bonobos, which are available in a non-invasive manner. Preliminary study showed that anti-LCV IgA but not IgG was efficiently and reproducibly detected in the feces of captive chimpanzees. It is noteworthy that the fecal IgA-positive individuals were seropositive for both anti-LCV IgG and IgA and that the IgA antibodies in both sera and feces were also detectable by Western blotting assay. These results indicate that the detection of fecal anti-LCV IgA is likely a reliable and feasible for epidemiological surveillance of LCV prevalence in the great apes. We then applied this method and found that 31% of wild bonobos tested were positive for anti-LCV IgA antibody in the feces. Notably, the positivity rates varied extensively among their sampled populations. In conclusion, our results in this study demonstrate that LCV is highly disseminated among wild bonobos while the prevalence is remarkably diverse in their population-dependent manner.

We are flat-faced hominins with an external nose that protrudes from the face. This feature was derived in the genus Homo, along with facial flattening and reorientation to form a high nasal cavity. The nasal passage conditions the inhaled air in terms of temperature and humidity to match the conditions required in the lung, and its anatomical variation is believed to be evolutionarily sensitive to the ambient atmospheric conditions of a given habitat. In this study, we used computational fluid dynamics (CFD) with three-dimensional topology models of the nasal passage under the same simulation conditions, to investigate air-conditioning performance in humans, chimpanzees, and macaques. The CFD simulation showed a horizontal straight flow of inhaled air in chimpanzees and macaques, contrasting with the upward and curved flow in humans. The inhaled air is conditioned poorly in humans compared with nonhuman primates. Virtual modifications to the human external nose topology, in which the nasal vestibule and valve are modified to resemble those of chimpanzees, change the airflow to be horizontal, but have little influence on the air-conditioning performance in humans. These findings suggest that morphological variation of the nasal passage topology was only weakly sensitive to the ambient atmosphere conditions; rather, the high nasal cavity in humans was formed simply by evolutionary facial reorganization in the divergence of Homo from the other hominin lineages, impairing the air-conditioning performance. Even though the inhaled air is not adjusted well within the nasal cavity in humans, it can be fully conditioned subsequently in the pharyngeal cavity, which is lengthened in the flat-faced Homo. Thus, the air-conditioning faculty in the nasal passages was probably impaired in early Homo members, although they have survived successfully under the fluctuating climate of the Plio-Pleistocene, and then they moved "Out of Africa" to explore the more severe climates of Eurasia.

Three strains TKU9, TKU49 and TKU50(T) , were isolated from the oral cavities of chimpanzees (Pan troglodytes). The isolates were all gram-positive, facultative anaerobic cocci that lacked catalase activity. Analysis of partial 16S rRNA gene sequences showed that the most closely related species was Streptococcus infantis (96.7%). The next most closely related species to the isolates were S. rubneri, S. mitis, S. peroris and S. australis (96.6 to 96.4%). Based on the rpoB and gyrB gene sequences, TKU50(T) was clustered with other member of the mitis group. Enzyme activity and sugar fermentation patterns differentiated this novel bacterium from other members of the mitis group streptococci. The DNA G + C content of strain TKU50(T) was 46.7 mol%, which is the highest reported value for members of the mitis group (40-46 mol%). On the basis of the phenotypic characterization, partial 16S rRNA gene and sequences data for two housekeeping gene (gyrB and rpoB), we propose a novel taxa, S. panodentis for TKU 50(T) (type strain = CM 30579(T)  = DSM 29921(T) ), for these newly described isolates., (© 2015 The Societies and Wiley Publishing Asia Pty Ltd.)

The nasal passages mainly adjust the temperature and humidity of inhaled air to reach the alveolar condition required in the lungs. By contrast to most other non-human primates, macaque monkeys are distributed widely among tropical, temperate and subarctic regions, and thus some species need to condition the inhaled air in cool and dry ambient atmospheric areas. The internal nasal anatomy is believed to have undergone adaptive modifications to improve the air-conditioning performance. Furthermore, the maxillary sinus (MS), an accessory hollow communicating with the nasal cavity, is found in macaques, whereas it is absent in most other extant Old World monkeys, including savanna monkeys. In this study, we used computational fluid dynamics simulations to simulate the airflow and heat and water exchange over the mucosal surface in the nasal passage. Using the topology models of the nasal cavity with and without the MS, we demonstrated that the MS makes little contribution to the airflow pattern and the air-conditioning performance within the nasal cavity in macaques. Instead, the inhaled air is conditioned well in the anterior portion of the nasal cavity before reaching the MS in both macaques and savanna monkeys. These findings suggest that the evolutionary modifications and coetaneous variations in the nasal anatomy are rather independent of transitions and variations in the climate and atmospheric environment found in the habitats of macaques., (© 2015. Published by The Company of Biologists Ltd.)

We discovered a lethal hemorrhagic syndrome arising from severe thrombocytopenia in Japanese macaques kept at the Primate Research Institute, Kyoto University. Extensive investigation identified that simian retrovirus type 4 (SRV-4) was the causative agent of the disease. SRV-4 had previously been isolated only from cynomolgus macaques in which it is usually asymptomatic. We consider that the SRV-4 crossed the so-called species barrier between cynomolgus and Japanese macaques, leading to extremely severe acute symptoms in the latter. Infectious agents that cross the species barrier occasionally amplify in virulence, which is not observed in the original hosts. In such cases, the new hosts are usually distantly related to the original hosts. However, Japanese macaques are closely related to cynomolgus macaques, and can even hybridize when given the opportunity. This lethal outbreak of a novel pathogen in Japanese macaques highlights the need to modify our expectations about virulence with regards crossing species barriers.

Recently, we discovered that alpha satellite DNA has unique and genus-specific localizations on the chromosomes of small apes. This study describes the details of alpha satellite localization in the genera Nomascus and Hylobates and explores their usefulness in distinguishing parental genome sets in hybrids between these genera. Fluorescence in situ hybridization was used to establish diagnostic criteria of alpha satellite DNA markers in discriminating small ape genomes. In particular we established the genus specificity of alpha satellite distribution in three species of light-cheeked gibbons (Nomascus leucogenys, N. siki, and N. gabriellae) in comparison to that of Hylobates lar. Then we determined the localization of alpha satellite DNA in a hybrid individual which resulted from a cross between these two genera. In Nomascus the alpha satellite DNA blocks were located at the centromere, telomere, and four interstitial regions. In Hylobates detectable amounts of alpha satellite DNA were seen only at centromeric regions. The differences in alpha satellite DNA locations between Nomascus and Hylobates allowed us to easily distinguish the parental chromosomal sets in the genome of intergeneric hybrid individuals found in Thai and Japanese zoos. Our study illustrates how molecular cytogenetic markers can serve as diagnostic tools to identify the origin of individuals. These molecular tools can aid zoos, captive breeding programs and conservation efforts in managing small apes species. Discovering more information on alpha satellite distribution is also an opportunity to examine phylogenetic and evolutionary questions that are still controversial in small apes.

An intracranial arachnoid cyst was detected in a 32-year-old, 44.6-kg, female chimpanzee at the Primate Research Institute, Kyoto University. Magnetic resonance imaging (MRI) and computed tomography (CT) were performed and the cognitive studies in which she participated were reviewed. MRI revealed that the cyst was present in the chimpanzee's right occipital convexity, and was located in close proximity to the posterior horn of the right lateral ventricle without ventriculomegaly. CT confirmed the presence of the cyst and no apparent signs indicating previous skull fractures were found. The thickness of the mandible was asymmetrical, whereas the temporomandibular joints and dentition were symmetrical. She showed no abnormalities in various cognitive studies since she was 3 years old, except a different behavioural pattern during a recent study, indicating a possible visual field defect. Detailed cognitive studies, long-term observation of her physical condition and follow-up MRI will be continued.

Deficits in the occipital cortex have varying consequences among mammalian species. Such variations are indicative of evolutionary transitions in the striate cortical contribution to visually guided behavior. However, little is known about the role of the striate cortex in visually guided behavior in chimpanzees due to ethical concerns about invasive experiments and methodological limitations such as the inability to monitor gaze movements. We had the opportunity to study the behavioral consequences of a deficit in the occipital cortex in a chimpanzee with a naturally occurring arachnoid cyst in her right occipital lobe. We assessed the chimpanzee's ability to detect a small light probe (0.5 visual degree, Michelson contrast > 0.9) presented at several locations in the visual field while monitoring gaze direction using an infra-red remote eye-tracker recently introduced to studies of great apes. The results showed the chimpanzee was unable to detect the probe in the lower left quadrant of the visual field, suggesting severe loss of contrast sensitivity in a part of hemivisual field that is retinotopically corresponded to the hemisphere of the cyst. A chimpanzee with a naturally occurring deficit in the right striate cortex and the availability of remote eye-tracking technology presented a unique opportunity to compare the role of the occipital lobe in visually guided behavior among various primate species., (© 2013 Published by Elsevier Ltd.)

Six strains, TKU 25, TKU 28, TKU 30, TKU 31(T), TKU 33 and TKU 34, were isolated from the oral cavity of a chimpanzee (Pan troglodytes). Colonies of strains grown on Mitis-Salivarius agar were similar in morphology to that of Streptococcus mutans. The novel strains were Gram-stain-positive, facultatively anaerobic cocci that lacked catalase activity. Analysis of the partial 16S rRNA gene sequences of these isolates showed that the most closely related strain was the type strain of S. mutans (96.4 %). The next closely related strains to the isolates were the type strains of Streptococcus devriesei (94.5 %) and Streptococcus downei (93.9 %). These isolates could be distinguished from S. mutans by inulin fermentation and alkaline phosphatase activity (API ZYM system). The peptidoglycan type of the novel isolates was Glu-Lys-Ala(3). Strains were not susceptible to bacitracin. On the basis of phenotypic characterization, partial 16S rRNA gene and two housekeeping gene (groEL and sodA) sequence data, we propose a novel taxon, Streptococcus troglodytae sp. nov.; the type strain is TKU 31(T) ( = JCM 18038(T) = DSM 25324(T)).

Emerging infectious diseases (EIDs) in wildlife are major threats both to human health and to biodiversity conservation. An estimated 71.8 % of zoonotic EID events are caused by pathogens in wildlife and the incidence of such diseases is increasing significantly in humans. In addition, human diseases are starting to infect wildlife, especially non-human primates. The chimpanzee is an endangered species that is threatened by human activity such as deforestation, poaching, and human disease transmission. Recently, several respiratory disease outbreaks that are suspected of having been transmitted by humans have been reported in wild chimpanzees. Therefore, we need to study zoonotic pathogens that can threaten captive chimpanzees in primate research institutes. Serological surveillance is one of several methods used to reveal infection history. We examined serum from 14 captive chimpanzees in Japanese primate research institutes for antibodies against 62 human pathogens and 1 chimpanzee-borne infectious disease. Antibodies tested positive against 29 pathogens at high or low prevalence in the chimpanzees. These results suggest that the proportions of human-borne infections may reflect the chimpanzee's history, management system in the institute, or regional epidemics. Furthermore, captive chimpanzees are highly susceptible to human pathogens, and their induced antibodies reveal not only their history of infection, but also the possibility of protection against human pathogens.