Search Results (145)

The ecological drivers of wildlife crop-foraging behavior—whether as a compensatory response to natural resource scarcity or as opportunistic exploitation of anthropogenic food sources—remain poorly understood in human–wildlife conflict research. Traditional methodologies, which primarily rely on direct observation and morphological identification, have limitations in comprehensively quantifying wildlife dietary composition, particularly in accurately distinguishing between morphologically similar plant species and conducting precise quantitative analyses. This study utilized DNA metabarcoding technology (rbcL gene markers) to identify and quantify plant dietary components through fecal sample analysis, systematically investigating the dietary composition and patterns of agricultural resource utilization of wild rhesus macaques (Macaca mulatta) in human–wildlife interface zones of southwestern China. A total of 29 rhesus macaque fecal samples were analyzed (15 from spring and 14 from winter), identifying 142 plant genera, comprising 124 wild plant genera, and 18 crop genera. The results revealed distinct seasonal foraging patterns: crops accounted for 32.11% of the diet in winter compared to 7.66% in spring. Notably, rhesus macaques continued to consume crops even during spring when wild resources were relatively abundant, challenging the traditional hypothesis driven by resource scarcity and suggesting that crop-foraging behavior may reflect an opportunistic, facultative resource selection strategy. This study demonstrates the significant value of DNA metabarcoding technology in wildlife foraging behavior research, providing scientific evidence for understanding human–primate conflict ecology and developing effective management strategies. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1–3% of the population globally. Owing to its multifactorial origin, complex genetics, and heterogeneity in clinical phenotypes, it is difficult to faithfully model ASD. In essence, ASD is an umbrella term for a group of individually rare disorders, each risk gene accounting for <1% of cases, threaded by a set of overlapping behavioral or molecular phenotypes. Validated behavioral tests are considered a gold standard for ASD diagnosis, and several animal models (rodents, pigs, and non-human primates) have traditionally been used to study its molecular basis. These models recapitulate the human phenotype to a varying degree and have been indispensable to preclinical research, but they cannot be used to study human-specific features such as protracted neuronal maturation and cell-intrinsic attributes, posing serious limitations to translatability. Human stem cell-based models, both as monolayer 2D cultures and 3D organoids and assembloids, can circumvent these limitations. Generated from a patient’s own reprogrammed cells, these can be used for testing therapeutic interventions that are more condition and patient relevant, targeting developmental windows where the intervention would be most effective. We discuss some of these advancements by comparing traditional and recent models of ASD. Full article

Background: Major Depressive Disorder represents a prevalent and critical mental health issue that highlights the pressing need for innovative therapeutic solutions. Recent research has identified dysfunction within the glutamate system as a crucial element influencing both the onset and management of depressive symptoms. Although TAK-653 is a new positive allosteric modulator of AMPA receptors, its effects have not been rigorously examined in models of depression in primates. Methods: To assess its potential antidepressant properties, a chronic unpredictable mild stress protocol was implemented over 12 weeks to create a monkey model of depression, followed by a two-week treatment period with TAK-653. Results: Behavioral evaluations showed that following stress exposure, the monkeys exhibited reduced motivation for food, increased huddling, diminished movement, and a tendency to remain at the lower levels of their enclosure. They also displayed heightened anxiety in response to external stimuli. Plasma analyses indicated higher levels of cortisol, IL-6, and IL-8 in the stressed monkeys compared to baseline readings, confirming the efficacy of the stress-inducing protocol. Post-treatment with TAK-653 resulted in significant improvements, such as enhanced motivation for food, less huddling behavior, greater activity, and a move towards the upper areas of the enclosure. Additionally, the plasma analysis revealed a marked decrease in cortisol and IL-6 levels, along with an increased expression of BDNF. Conclusions: These findings indicate that TAK-653 effectively alleviates depression-like behaviors in nonhuman primate models, thereby paving the way for a promising new strategy in the treatment of depression. Full article

Research involving non-human primates remains a cornerstone in fields such as biomedical research and systems neuroscience. However, the daily routines of laboratory work can induce stress in these animals, potentially compromising their well-being and the reliability of experimental outcomes. To address this, many laboratories have adopted home-cage training protocols to mitigate stress caused by routine procedures such as transport and restraint—a factor that can impact both macaque physiology and experimental validity. This review explores the primary methods and experimental setups employed in home-cage training, highlighting their potential not only to address ethical concerns surrounding animal welfare but also to reduce training time and risks for the researchers. Furthermore, by combining home-cage training with wireless recordings, it becomes possible to expand research opportunities in behavioral neurophysiology with non-human primates. This approach enables the study of various cognitive processes in more naturalistic settings, thereby increasing the ecological validity of scientific findings through innovative experimental designs that thoroughly investigate the complexity of the animals’ natural behavior. Full article

Background: Behavioral, social, and physical characteristics are posited to distinguish the sexes, yet research on transcription-level sexual differences in the brain is limited. Here, we investigated sexually divergent brain transcriptomics in pre-pubertal cynomolgus macaques, a commonly used surrogate species to humans. Methods: A transcriptomic profile using RNA sequencing was generated for the temporal lobe, ventral midbrain, and cerebellum of three female and three male cynomolgus macaques previously treated with an adeno-associated virus vector mix. Statistical analyses to determine differentially expressed protein-coding genes in all three lobes were conducted using DeSeq2 with a false-discovery-rate-corrected p-value of 0.05. Results: We identified target genes in the temporal lobe, ventral midbrain, and cerebellum with functions in translation, immunity, behavior, and neurological disorders that exhibited statistically significant sexually divergent expression. Conclusions: We provide potential mechanistic insights into the epidemiological differences observed between the sexes with regard to mental health and infectious diseases, such as COVID-19. Our results provide pre-pubertal information on sexual differences in non-human primate brain transcriptomics and may provide insight into health disparities between the biological sexes in humans. Full article

Background: The therapeutic blockade of the PD1/PD-L1 axis with monoclonal antibodies has led to a breakthrough in cancer treatment, as it plays a key role in the immune evasion of tumors. Nevertheless, treating patients with cancer with vaccines that stimulate a targeted immune response is another attractive approach for which few side effects have been observed in combination immunotherapy clinical trials. In this sense, our group has recently developed a therapeutic cancer vaccine candidate called PKPD-L1^Vac which contains as an antigen the extracellular domain of human PD-L1 fused to a 47 amino-terminal, part of the LpdA gene of N. meningitides, which is produced in E. coli. The investigation of potential toxicities associated with PD-L1 blockade by a new therapy in preclinical studies is critical to optimizing the efficacy and safety of that new therapy. Methods: Here, we describe immunogenicity and preliminary safety studies in mice, rats, rabbits, and non-human primates that make use of a 200 μg dose of PKPD-L1 in combination with VSSPs or alum phosphate to contribute to the assessment of potential adverse events that are relevant to the future clinical development program of this novel candidate. Results: The administration of PKPD-L1^Vac to the four species at the doses studied was immunogenic and did not result in behavioral, clinical, hematological, or serum biochemical changes. Conclusions: Therefore, PKPD-L1^Vac could be considered suitable for further complex toxicological studies and the way for its clinical evaluation in humans has been opened. Full article

The motor cortex of non-human primates plays a key role in brain–machine interface (BMI) research. In addition to recording cortical neural signals, accurately and efficiently capturing the hand movements of experimental animals under unconstrained conditions remains a key challenge. Addressing this challenge can deepen our understanding and application of BMI behavior from both theoretical and practical perspectives. To address this issue, we developed a deep learning framework that combines Yolov5 and RexNet-ECA to reliably detect the hand joint positions of freely moving primates at different distances using a single camera. The model simplifies the setup procedure while maintaining high accuracy, with an average keypoint detection error of less than three pixels. Our method eliminates the need for physical markers, ensuring non-invasive data collection while preserving the natural behavior of the experimental subjects. The proposed system exhibits high accuracy and ease of use compared to existing methods. By quickly and accurately acquiring spatiotemporal behavioral metrics, the method provides valuable insights into the dynamic interplay between neural and motor functions, further advancing BMI research. Full article

Objectives: Annexin-A1 is a 37 kDa phospholipid-binding protein which is concentrated in a truncated 34 kDa form (AnnA1) in caveolae on the tumor vascular endothelial cell surface with expression in many tumor types. PRISM developed the monoclonal mouse antibody mAnnA1 against AnnA1 for evaluation of AnnA1 as a potential target for imaging and therapy in oncology. mAnnA1 was humanized to make hAnnA1 for translation to clinical studies. Both PRISM-produced mAnnA1 and cGMP contractor-produced hAnnA1 were investigated using noninvasive PET/CT imaging, and dosimetry was evaluated to enable clinical translation of this strategy and to investigate in vivo behavior of hAnnA1. Methods: Antibodies mAnnA1 and hAnnA1 (PRISM “hAnnA1-P” or contractor generated “hAnnA1-C”) were conjugated with the chelator deferoxamine and evaluated for immunoreactivity with ELISA. Conjugated antibodies were radiolabeled with zirconium-89. Naïve mice, rats, and non-human primates (NHP) were injected with [⁸⁹Zr]mAnnA1 or [⁸⁹Zr]hAnnA1 and imaged with PET/CT up to 10 days post injection. After imaging, mice and rats were euthanized and organs were collected, weighed, and radioactivity was quantified using a gamma counter. Dosimetry in mice and NHPs were calculated using OLINDA. Results: [⁸⁹Zr]mAnnA1 showed similar biodistribution to other antibodies with slow clearance through the liver. Transition to [⁸⁹Zr]hAnnA1-C during the dosimetry studies revealed substantial uptake in the spleen (130 ± 48% ID/g at day 5 post injection in female BALB/c), which was not observed with [⁸⁹Zr]mAnnA1 (5.6 ± 1.7% ID/g at day 7 PI). Further studies in multiple strains of mice showed variable elevated splenic uptake of [⁸⁹Zr]hAnnA1-C across mouse strains, with the highest uptake observed in female BALB/c mice (118.4 ± 23.1% ID/g) and the lowest uptake observed in male CD1 mice (34.7 ± 10.2% ID/g). Additionally, splenic uptake of hAnnA1-C was observed in Fischer rats (2.8 ± 0.6% ID/organ) and NHPs (1.6 ± 0.6% ID/organ), although at lower levels than what was observed in BALB/c mice (8.8 ± 1.8% ID/organ). Dosimetry results showed similar values between estimates based on mouse and NHP data, with the largest difference seen in the spleen (5.2 vs. 2.6 mSv/MBq in females respectively). Sequencing of hAnnA1-C revealed a frameshift mutation in the antibody sequence introduced during cGMP manufacture. Restoration of the antibody sequence by PRISM returned the antibody distribution into alignment with mAnnA1. Conclusions: An aberration introduced during cGMP production of hAnnA1-C resulted in increased splenic uptake and alteration of the biodistribution in mice. PET imaging enabled quantitative detection of the immunogenic behavior of hAnnA1, which led to detection of the sequence error. Restoration of the sequence resulted in an antibody which was non-immunogenic to mice. Full article

Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder, affecting approximately 25–35% of individuals exposed to significant psychological trauma. Despite extensive research, the underlying biological mechanisms of PTSD remain poorly understood, and the effectiveness of trauma-focused psychotherapeutic interventions is limited. To date, animal studies investigating trauma responses have primarily relied on rodent models, with the potential contributions of non-human primates relatively neglected. In this study, matched-control observations were employed to examine maternal caregiving behaviors, prosocial interactions, and responses to alarm calls in free-ranging golden snub-nosed monkeys (Rhinopithecus roxellana) before and after an infanticide event. Results indicated a significant decrease in prosocial behaviors among some mothers, accompanied by significant increases in caregiving behaviors, heightened responsiveness to alarm calls, and indications of low mood. These findings provide evidence of trauma-related behavioral changes in golden snub-nosed monkeys, underscoring their utility as a model for studying PTSD given the similarity to trauma responses observed in humans. Overall, this study provides a foundation for further investigation into the evolutionary and biological aspects of PTSD, as well as the interactions between species-specific trauma responses. Future research should explore the use of non-human primate models to deepen our understanding of PTSD mechanisms. Full article

The sublingua is an anatomical structure located under the tongue. This rare organ can be present in some animals as a rudimentary structure, but among prosimian primates, such as lemurs and lorises, it is fully developed. In addition to the sublingua, prosimians have modified lower incisors and canines called “dental comb”. The anatomy of sublingua has been studied macro and microanatomically since the early 19th century. Most authors argue that the sublingua is an oral morphological adaptation to develop a toothbrush’s role in cleaning the dental comb. However, others assert that the functional role has yet to be established. Comparative studies of macro and microanatomy are scarce or incomplete for primates; thus, the putative function remains unclear. To better understand the functional significance of the sublingua, we studied this structure in Lemur catta and Varecia variegata specimens using histochemical staining techniques and scanning electron microscopy with microanalysis. The new data obtained provide a fuller picture of the role assigned to sublingua so far, which could be more complex. In light of the morphological findings, we should consider additional roles/functions of the sublingua, including but not limited to food processing, grooming or social behavior. Full article

Social housing provides a high level of enrichment for captive non-human primates, but providing this in research situations can be challenging. We have developed a multifactorial animal selection and introduction process coordinated by veterinary and animal care behavioral teams. This process sought to successfully establish lasting same-sex pairs and trios for African green monkeys (Chlorocebus sabaeus) in studies lasting from three months to over a year. The selection and introduction process addresses variables that impact a successful grouping, including age, animal weight difference, cage size and configuration. Evaluation and consideration of these initial matchmaking parameters has favorably enhanced pairing/trio bonding. Social housing with females has been typically more successful than with males, with 90–100% of females successfully pair- or trio-housed. Successful pairs and trios exhibit multiple affiliative behaviors and demonstrate better overall health while under study, ensuring benefits both to animal welfare and study data. Full article

Research facilities have established animal adoption programs for laboratory animals. However, adoption to private owners is not an option for non-human primates (NHPs), so their post-research life presents a unique challenge. Here, we describe a collaborative effort between laboratory animal veterinarians and behavioral management staff in retiring NHPs in place to ensure their quality of life after the completion of research projects. The success of our retirement program hinges on our collaborative efforts to manage clinical diseases such as arthritis, amyloidosis, and diarrhea; to surgically ex-plant previous research hardware; and to evaluate the animals’ behavior and temperament to ensure each individual is placed in a new group or living situation in which they are likely to be successful and to have good welfare. Implementation of a quality-of-life assessment tool for all retired animals allows all staff involved in the animals’ care to proactively and periodically assess the quality of life of these animals. The successful retirement of NHPs living in social groups is rewarding for all personnel and promotes a culture of caring. Research animal retirement is an important way for us to give back and honor the contributions these animals have made to advancing medicine. Full article

Cynomolgus macaques (Macaca fascicularis; Mf) serve an essential role in the advancement of biomedical research. Aged macaques, in particular, are highly valued as animal models for the study of geriatric diseases. While social housing has become the default for nonhuman primates (NHPs), socially housing sexually mature males poses a unique challenge. Moreover, socially housing aged males that have been previously kept in single housing may pose even greater challenge and risk due to a higher likelihood of aggression. Temperament assessment plays an integral part in determining the success of social housing arrangements of NHPs. In this paper, we report our work at the Primate Research Center of IPB University in integrating behavior observation and veterinary management to socially house adult, male Mf. We describe our experience in successfully housing young-adult, male Mf (n = 8–10, aged 6 years) for over 2.5 years, and the multiple efforts to socially house a small group of previously singly housed aged, male Mf (n = 6, aged >15 years). The temperament of each Mf was considered in the planning and implementation of social housing attempts. While a simplified behavioral observation was performed for the young adults, a more rigorous PAIR-T assessment was performed on the aged Mf. A group formation was initially attempted, aiming to achieve a small group of six aged, male Mf. While this group at first showed promising outcomes, significant incidents of aggression required regrouping as pairs or triads wherein the subject combinations were determined based on temperament and dominance. A total of three attempts were made to house these aged Mf in a small group throughout the course of 17 months, and the results showed that at our facility, aged, male Mf are best housed as triads or pairs, with selections based on their temperament and dominance compatibility. We concluded that behavioral assessments and veterinary management are pivotal in supporting the social housing efforts of adult, male Mf in order to optimize their well-being. Full article

Effective management of captive M. fascicularis (long-tailed macaques) is crucial for maintaining high-quality research models, necessitating strategies to promote their welfare. This study evaluated the impact of a foraging enrichment device, the “fire hose square knot browser”, on the behavior of 32 long-tailed macaques at the Primate Research Center of IPB University in Bogor, Indonesia. We observed and analyzed daily behaviors across various food types over 288 h using scan and instantaneous sampling methods. Statistical analyses, including ANOVA and Kruskal–Wallis tests, revealed significant behavioral changes in the presence of the foraging enrichment device. The foraging enrichment device notably increased eating and affiliative behaviors, while reducing resting, agonistic, and stereotypic behaviors. No significant differences in eating, auto-grooming, resting, sexual, agonistic, or stereotypic behaviors were observed between the morning and afternoon. However, mobility and affiliation behaviors varied between these periods. The highest percentage of eating behavior occurred with the enrichment foraging device and a mixture of fruits. Furthermore, a three-way non-parametric analysis suggests a significant effect of food type and treatment on behaviors such as mobility and stereotyping. These findings underscore the positive impact of foraging enrichment devices on promoting active behavior and enhancing animal welfare in captive long-tailed macaques. Full article

Chimp Haven is a private, nonprofit organization that serves as the largest chimpanzee sanctuary in the world. The National Institutes of Health supports the federal sanctuary system, which is operated by Chimp Haven, to provide lifetime care for chimpanzees who have retired from biomedical research. Chimp Haven is home to over 300 chimpanzees, with a wide variety of individual health needs including infectious diseases. The chimpanzees live in large, mixed-sex social groups within corrals, multi-dimensional enclosures, and naturally forested habitats, which presents challenges for monitoring and balancing individual versus group needs. Primate veterinarians and animal behavior directors have an obligation to collaborate for the best possible health and welfare outcomes for the species in their care. This manuscript details how veterinarians and behavioral staff at Chimp Haven interface to enhance clinical management and improve chimpanzee welfare using two clinical cases to illustrate this relationship. This is accomplished through the development of individual care plans that include the utilization of welfare assessment metrics and positive reinforcement training programs collaboratively developed between the veterinarians and behaviorists to facilitate voluntary medical procedures without the need for social isolation. Specifically, welfare metrics such as monitoring chimpanzee wounding levels and severity, as well as targeted assessments, involve the input of both the veterinarians and behaviorists. Positive reinforcement training initiatives such as weight loss, heart health, and wound care also require the interface between the two disciplines. The authors aim to demonstrate that working together provides optimal levels of expert care for both the physical and mental health of the chimpanzees in our care. Full article