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The progressive degradation in the trabecular meshwork (TM) is related to age-related ocular diseases like primary open-angle glaucoma. However, the molecular basis and biological significance of the aging process in TM have not been fully elucidated. Here, we established a dynamic single-cell transcriptomic landscape of aged macaque TM, wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM aging. Furthermore, we divided TM cells into 13 clusters and performed an in-depth analysis on cluster 0, which had the highest aging score and the most significant changes in cell proportions between the two groups. Ultimately, we found that the APOE gene was an important differentially expressed gene in cluster 0 during the aging process, highlighting the close relationship between cell migration and extracellular matrix regulation, and TM function. Our work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components, thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal range. Our work provides valuable insights for future clinical diagnosis and treatment of glaucoma. [ABSTRACT FROM AUTHOR]

Marburg virus infection in humans is associated with case fatality rates that can reach up to 90%, but to date, there are no approved vaccines or monoclonal antibody (mAb) countermeasures. Here, we immunized Rhesus macaques with multivalent combinations of filovirus glycoprotein (GP) antigens belonging to Marburg, Sudan, and Ebola viruses to generate monospecific and cross-reactive antibody responses against them. From the animal that developed the highest titers of Marburg virus GP-specific neutralizing antibodies, we sorted single memory B cells using a heterologous Ravn virus GP probe and cloned and characterized a panel of 34 mAbs belonging to 28 unique lineages. Antibody specificities were assessed by overlapping pepscan and binding competition analyses, revealing that roughly a third of the lineages mapped to the conserved receptor binding region, including potent neutralizing lineages that were confirmed by negative stain electron microscopy to target this region. Additional lineages targeted a protective region on GP2, while others were found to possess cross-filovirus reactivity. Our study advances the understanding of orthomar-burgvirus glycoprotein antigenicity and furthers efforts to develop candidate antibody countermeasures against these lethal viruses. IMPORTANCE Marburg viruses were the first filoviruses characterized to emerge in humans in 1967 and cause severe hemorrhagic fever with average case fatality rates of ~50%. Although mAb countermeasures have been approved for clinical use against the related Ebola viruses, there are currently no approved countermeasures against Marburg viruses. We successfully isolated a panel of orthomarburgvirus GP-specific mAbs from a macaque immunized with a multivalent combination of filovirus antigens. Our analyses revealed that roughly half of the antibodies in the panel mapped to regions on the glycoprotein shown to protect from infection, including the host cell receptor binding domain and a protective region on the membrane-anchoring subunit. Other antibodies in the panel exhibited broad filovirus GP recognition. Our study describes the discovery of a diverse panel of cross-reactive macaque antibodies targeting orthomarburgvirus and other filovirus GPs and provides candidate immunotherapeutics for further study and development. [ABSTRACT FROM AUTHOR]

• A non-human primate model of maternal immune activation (MIA) and neurodevelopment. • Offspring previously shown to have reduced frontal volumes and cognitive impairments. • Here, prefrontal n-acetylaspartate (NAA) is elevated across childhood and adolescence. • Elevated NAA correlates with less impaired cognition in these male MIA offspring. • Elevated prefrontal NAA may reflect a resilience-related process in MIA offspring. Converging data show that exposure to maternal immune activation (MIA) in utero alters brain development in animals and increases the risk of neurodevelopmental disorders in humans. A recently developed non-human primate MIA model affords opportunities for studies with uniquely strong translational relevance to human neurodevelopment. The current longitudinal study used 1H-MRS to investigate the developmental trajectory of prefrontal cortex metabolites in male rhesus monkey offspring of dams (n = 14) exposed to a modified form of the inflammatory viral mimic, polyinosinic:polycytidylic acid (Poly IC), in the late first trimester. Brain metabolites in these animals were compared to offspring of dams that received saline (n = 10) or no injection (n = 4). N-acetylaspartate (NAA), glutamate, creatine, choline, myo-inositol, taurine, and glutathione were estimated from PRESS and MEGA-PRESS acquisitions obtained at 6, 12, 24, 36, and 45 months of age. Prior investigations of this cohort reported reduced frontal cortical gray and white matter and subtle cognitive impairments in MIA offspring. We hypothesized that the MIA-induced neurodevelopmental changes would extend to abnormal brain metabolite levels, which would be associated with the observed cognitive impairments. Prefrontal NAA was significantly higher in the MIA offspring across all ages (p < 0.001) and was associated with better performance on the two cognitive measures most sensitive to impairment in the MIA animals (both p < 0.05). Myo-inositol was significantly lower across all ages in MIA offspring but was not associated with cognitive performance. Taurine was elevated in MIA offspring at 36 and 45 months. Glutathione did not differ between groups. MIA exposure in male non-human primates is associated with altered prefrontal cortex metabolites during childhood and adolescence. A positive association between elevated NAA and cognitive performance suggests the hypothesis that elevated NAA throughout these developmental stages reflects a protective or resilience-related process in MIA-exposed offspring. The potential relevance of these findings to human neurodevelopmental disorders is discussed. [ABSTRACT FROM AUTHOR]

Abstract Heart rate (HR) and respiration rate (RR) play an important role in the study of complex behaviors and their physiological correlations in non-human primates (NHPs). However, collecting HR and RR information is often challenging, involving either invasive implants or tedious behavioral training, and there are currently few established simple and non-invasive techniques for HR and RR measurement in NHPs owing to their stress response or indocility. In this study, we employed a frequency-modulated continuous wave (FMCW) radar to design a novel contactless HR and RR monitoring system. The designed system can estimate HR and RR in real time by placing the FMCW radar on the cage and facing the chest of both awake and anesthetized macaques, the NHP investigated in this study. Experimental results show that the proposed method outperforms existing methods, with averaged absolute errors between the reference monitor and radar estimates of 0.77 beats per minute (bpm) and 1.29 respirations per minute (rpm) for HR and RR, respectively. In summary, we believe that the proposed non-invasive and contactless estimation method could be generalized as a HR and RR monitoring tool for NHPs. Furthermore, after modifying the radar signal-processing algorithms, it also shows promise for applications in other experimental animals for animal welfare, behavioral, neurological, and ethological research.

Abstract The dorsal pulvinar has been implicated in visuospatial attentional and perceptual confidence processing. Pulvinar lesions in humans and monkeys lead to spatial neglect symptoms, including an overt spatial saccade bias during free choices. However, it remains unclear whether disrupting the dorsal pulvinar during target selection that relies on a perceptual decision leads to a perceptual impairment or a more general spatial orienting and choice deficit. To address this question, we reversibly inactivated the unilateral dorsal pulvinar by injecting GABA-A agonist THIP while two macaque monkeys performed a color discrimination saccade task with varying perceptual difficulty. We used Signal Detection Theory and simulations to dissociate perceptual sensitivity (d-prime) and spatial selection bias (response criterion) effects. We expected a decrease in d-prime if dorsal pulvinar affects perceptual discrimination and a shift in response criterion if dorsal pulvinar is mainly involved in spatial orienting. After the inactivation, we observed response criterion shifts away from contralesional stimuli, especially when two competing stimuli in opposite hemifields were present. Notably, the d-prime and overall accuracy remained largely unaffected. Our results underline the critical contribution of the dorsal pulvinar to spatial orienting and action selection while showing it to be less important for visual perceptual discrimination.

Abstract Necrophilic behavior (attempted copulation with corpses) has been scarcely reported in non-human primates, especially in the wild. Here is the first case of necrophilic behavior observed in wild stump-tailed macaques in Thailand. Six groups of total N > 460 individuals have been identified and habituated. The corpse of an adult female was found and directly observed for 2 days and by camera trap for 3 days. The cause of death could not be identified, but no prominent physical injury was detected. Within 3 days of the observation, three different males attempted copulation with the corpse. Noteworthy for this observation was that not only males in the group of the dead female but also males from different groups interacted with the corpse. Taken together, these observations suggest that some cues emanating from the corpse coupled with a nonresistant/passive orientation may have triggered these responses in the males. Given that necrophiliac responses have been scarcely reported in non-human primates, our findings provide new insight into these behaviors and to comparative thanatology in general.

Social communication draws on several cognitive functions such as perception, emotion recognition and attention. The association of audio‐visual information is essential to the processing of species‐specific communication signals. In this study, we use functional magnetic resonance imaging in order to identify the subcortical areas involved in the cross‐modal association of visual and auditory information based on their common social meaning. We identified three subcortical regions involved in audio‐visual processing of species‐specific communicative signals: the dorsolateral amygdala, the claustrum and the pulvinar. These regions responded to visual, auditory congruent and audio‐visual stimulations. However, none of them was significantly activated when the auditory stimuli were semantically incongruent with the visual context, thus showing an influence of visual context on auditory processing. For example, positive vocalization (coos) activated the three subcortical regions when presented in the context of positive facial expression (lipsmacks) but not when presented in the context of negative facial expression (aggressive faces). In addition, the medial pulvinar and the amygdala presented multisensory integration such that audiovisual stimuli resulted in activations that were significantly higher than those observed for the highest unimodal response. Last, the pulvinar responded in a task‐dependent manner, along a specific spatial sensory gradient. We propose that the dorsolateral amygdala, the claustrum and the pulvinar belong to a multisensory network that modulates the perception of visual socioemotional information and vocalizations as a function of the relevance of the stimuli in the social context. Significance statement: Understanding and correctly associating socioemotional information across sensory modalities, such that happy faces predict laughter and escape scenes predict screams, is essential when living in complex social groups. With the use of functional magnetic imaging in the awake macaque, we identify three subcortical structures—dorsolateral amygdala, claustrum and pulvinar—that only respond to auditory information that matches the ongoing visual socioemotional context, such as hearing positively valenced coo calls and seeing positively valenced mutual grooming monkeys. We additionally describe task‐dependent activations in the pulvinar, organizing along a specific spatial sensory gradient, supporting its role as a network regulator. [ABSTRACT FROM AUTHOR]

Heart rate (HR) and respiration rate (RR) play an important role in the study of complex behaviors and their physiological correlations in non-human primates (NHPs). However, collecting HR and RR information is often challenging, involving either invasive implants or tedious behavioral training, and there are currently few established simple and non-invasive techniques for HR and RR measurement in NHPs owing to their stress response or indocility. In this study, we employed a frequency-modulated continuous wave (FMCW) radar to design a novel contactless HR and RR monitoring system. The designed system can estimate HR and RR in real time by placing the FMCW radar on the cage and facing the chest of both awake and anesthetized macaques, the NHP investigated in this study. Experimental results show that the proposed method outperforms existing methods, with averaged absolute errors between the reference monitor and radar estimates of 0.77 beats per minute (bpm) and 1.29 respirations per minute (rpm) for HR and RR, respectively. In summary, we believe that the proposed non-invasive and contactless estimation method could be generalized as a HR and RR monitoring tool for NHPs. Furthermore, after modifying the radar signal-processing algorithms, it also shows promise for applications in other experimental animals for animal welfare, behavioral, neurological, and ethological research. [ABSTRACT FROM AUTHOR]

Cytoarchitecture, the organization of cells within organs and tissues, serves as a crucial anatomical foundation for the delineation of various regions. It enables the segmentation of the cortex into distinct areas with unique structural and functional characteristics. While traditional 2D atlases have focused on cytoarchitectonic mapping of cortical regions through individual sections, the intricate cortical gyri and sulci demands a 3D perspective for unambiguous interpretation. In this study, we employed fluorescent micro-optical sectioning tomography to acquire architectural datasets of the entire macaque brain at a resolution of 0.65 µm × 0.65 µm × 3 µm. With these volumetric data, the cortical laminar textures were remarkably presented in appropriate view planes. Additionally, we established a stereo coordinate system to represent the cytoarchitectonic information as surface-based tomograms. Utilizing these cytoarchitectonic features, we were able to three-dimensionally parcel the macaque cortex into multiple regions exhibiting contrasting architectural patterns. The whole-brain analysis was also conducted on mice that clearly revealed the presence of barrel cortex and reflected biological reasonability of this method. Leveraging these high-resolution continuous datasets, our method offers a robust tool for exploring the organizational logic and pathological mechanisms of the brain's 3D anatomical structure. [ABSTRACT FROM AUTHOR]

The dorsal pulvinar has been implicated in visuospatial attentional and perceptual confidence processing. Pulvinar lesions in humans and monkeys lead to spatial neglect symptoms, including an overt spatial saccade bias during free choices. However, it remains unclear whether disrupting the dorsal pulvinar during target selection that relies on a perceptual decision leads to a perceptual impairment or a more general spatial orienting and choice deficit. To address this question, we reversibly inactivated the unilateral dorsal pulvinar by injecting GABA-A agonist THIP while two macaque monkeys performed a color discrimination saccade task with varying perceptual difficulty. We used Signal Detection Theory and simulations to dissociate perceptual sensitivity (d-prime) and spatial selection bias (response criterion) effects. We expected a decrease in d-prime if dorsal pulvinar affects perceptual discrimination and a shift in response criterion if dorsal pulvinar is mainly involved in spatial orienting. After the inactivation, we observed response criterion shifts away from contralesional stimuli, especially when two competing stimuli in opposite hemifields were present. Notably, the d-prime and overall accuracy remained largely unaffected. Our results underline the critical contribution of the dorsal pulvinar to spatial orienting and action selection while showing it to be less important for visual perceptual discrimination. [ABSTRACT FROM AUTHOR]

The claustrum is an ancient telencephalic subcortical structure displaying extensive, reciprocal connections with much of the cortex and receiving projections from thalamus, amygdala, and hippocampus. This structure has a general role in modulating cortical excitability and is considered to be engaged in different cognitive and motor functions, such as sensory integration and perceptual binding, salience-guided attention, top-down executive functions, as well as in the control of brain states, such as sleep and its interhemispheric integration. The present study is the first to describe in detail a projection from the claustrum to the striatum in the macaque brain. Based on tracer injections in different striatal regions and in different cortical areas, we observed a rough topography of the claustral connectivity, thanks to which a claustral zone projects to both a specific striatal territory and to cortical areas involved in a network projecting to the same striatal territory. The present data add new elements of complexity of the basal ganglia information processing mode in motor and non-motor functions and provide evidence for an influence of the claustrum on both cortical functional domains and cortico-basal ganglia circuits. [ABSTRACT FROM AUTHOR]

Necrophilic behavior (attempted copulation with corpses) has been scarcely reported in non-human primates, especially in the wild. Here is the first case of necrophilic behavior observed in wild stump-tailed macaques in Thailand. Six groups of total N > 460 individuals have been identified and habituated. The corpse of an adult female was found and directly observed for 2 days and by camera trap for 3 days. The cause of death could not be identified, but no prominent physical injury was detected. Within 3 days of the observation, three different males attempted copulation with the corpse. Noteworthy for this observation was that not only males in the group of the dead female but also males from different groups interacted with the corpse. Taken together, these observations suggest that some cues emanating from the corpse coupled with a nonresistant/passive orientation may have triggered these responses in the males. Given that necrophiliac responses have been scarcely reported in non-human primates, our findings provide new insight into these behaviors and to comparative thanatology in general. [ABSTRACT FROM AUTHOR]

Decades of studies robustly support a critical role for the hippocampus in spatial memory across a wide range of species. Hippocampal damage produces clear and consistent deficits in allocentric spatial memory that requires navigating through space in rodents, non‐human primates, and humans. By contrast, damage to the hippocampus spares performance in most non‐navigational spatial memory tasks—which can typically be resolved using egocentric cues. We previously found that transient inactivation of the hippocampus impairs performance in the Hamilton Search Task (HST), a self‐ordered non‐navigational spatial search task. A key question, however, still needs to be addressed. Acute, reversible inactivation of the hippocampus may have resulted in an impairment in the HST because this approach does not allow for neuroplastic compensation, may prevent the development of an alternative learning strategy, and/or may produce network‐based effects that disrupt performance. We compared learning and performance on the HST in male rhesus macaques (six unoperated control animals and six animals that underwent excitotoxic lesions of the hippocampus). We found a significant impairment in animals with hippocampal lesions. While control animals improved in performance over the course of 45 days of training, performance in animals with hippocampal lesions remained at chance levels. The HST thus represents a sensitive assay for probing the integrity of the hippocampus in non‐human primates. These data provide evidence demonstrating that the hippocampus is critical for this type of non‐navigational spatial memory, and help to reconcile the many null findings previously reported. [ABSTRACT FROM AUTHOR]

Simple Summary: Monkeys in urban spaces are often labeled as 'pests' by people who share spaces with them, mainly driven by their behavior to adapt and survive in a human-dominated environment. In Malaysia, there has been an increase in complaints about urban monkeys, which drives management strategies mainly to reduce human populations that impact the animals' welfare and conservation. Understanding the dynamics between monkeys, people, and the urban ecosystem is the first step to identifying the drivers of the complaints. This study investigates the types of ecological activities of the long-tailed macaque (Macaca fascicularis) at an urban tourism site and how human activity influences it. Monkeys were impacted negatively by the presence of humans. Less affiliative interactions were performed when human traffic was high; for example, less social behavior was seen in the group. The monkeys also used anthropogenic structures predominantly when people were present and would spend time on natural structures when people were not. This study supports evidence that monkeys alter behaviors to adapt to living in urban spaces. A structured management plan needs to consider these dynamics to manage complaints. The increasing overlap of resources between human and long-tailed macaque (Macaca fascicularis) (LTM) populations have escalated human–primate conflict. In Malaysia, LTMs are labeled as a 'pest' species due to the macaques' opportunistic nature. This study investigates the activity budget of LTMs in an urban tourism site and how human activities influence it. Observational data were collected from LTMs daily for a period of four months. The observed behaviors were compared across differing levels of human interaction, between different times of day, and between high, medium, and low human traffic zones. LTMs exhibited varying ecological behavior patterns when observed across zones of differing human traffic, e.g., higher inactivity when human presence is high. More concerning is the impact on these animals' welfare and group dynamics as the increase in interactions with humans takes place; we noted increased inactivity and reduced intra-group interaction. This study highlights the connection that LTMs make between human activity and sources of anthropogenic food. Only through understanding LTM interaction can the cause for human–primate conflict be better understood, and thus, more sustainable mitigation strategies can be generated. [ABSTRACT FROM AUTHOR]

Briefly discusses the causes of unfavourable interactions between humans and free-living non-human primates, and alternatives to lethal methods of resolving these.

BackgroundEpidemiological studies suggest that maternal immune activation (MIA) is a significant risk factor for future neurodevelopmental disorders, including schizophrenia (SZ), in offspring. Consistent with findings in SZ research and work in rodent systems, preliminary cross-sectional findings in nonhuman primates suggest that MIA is associated with dopaminergic hyperfunction in young adult offspring.MethodsIn this unique prospective longitudinal study, we used [18F]fluoro-l-m-tyrosine positron emission tomography to examine the developmental time course of striatal presynaptic dopamine synthesis in male rhesus monkeys born to dams (n = 13) injected with a modified form of the inflammatory viral mimic, polyinosinic:polycytidylic acid [poly(I:C)], in the late first trimester. Striatal (caudate, putamen, and nucleus accumbens) dopamine from these animals was compared with that of control offspring born to dams that received saline (n = 10) or no injection (n = 4). Dopamine was measured at 15, 26, 38, and 48 months of age. Prior work with this cohort found decreased prefrontal gray matter volume in MIA offspring versus controls between 6 and 45 months of age. Based on theories of the etiology and development of SZ-related pathology, we hypothesized that there would be a delayed (relative to the gray matter decrease) increase in striatal fluoro-l-m-tyrosine signal in the MIA group versus controls.Results[18F]fluoro-l-m-tyrosine signal showed developmental increases in both groups in the caudate and putamen. Group comparisons revealed significantly greater caudate dopaminergic signal in the MIA group at 26 months.ConclusionsThese findings are highly relevant to the known pathophysiology of SZ and highlight the translational relevance of the MIA model in understanding mechanisms by which MIA during pregnancy increases risk for later illness in offspring.

IntroductionRhesus macaques are natural hosts to multiple viruses including rhesus cytomegalovirus (RhCMV), rhesus rhadinovirus (RRV), and Simian Foamy Virus (SFV). While viral infections are ubiquitous, viral transmissions to uninfected animals are incompletely defined. Management procedures of macaque colonies include cohorts that are Specific Pathogen Free (SPF). Greater understanding of viral transmission would augment SPF protocols. Moreover, vaccine/challenge studies of human viruses would be enhanced by leveraging transmission of macaque viruses to recapitulate expected challenges of human vaccine trials.Materials and methodsThis study characterizes viral transmissions to uninfected animals following inadvertent introduction of RhCMV/RRV/SFV-infected adults to a cohort of uninfected juveniles. Following co-housing with virus-positive adults, juveniles were serially evaluated for viral infection.ResultsHorizontal viral transmission was rapid and absolute, reaching 100% penetrance between 19 and 78 weeks.ConclusionsThis study provides insights into viral natural histories with implications for colony management and modeling vaccine-mediated immune protection studies.

Abstract Background Recent studies have shown that umbilical cord mesenchymal stem cells have an anti-aging effect in ovaries, but the cellular and molecular mechanisms of HA-MSC ovarian anti-aging remain to be studied. Therefore, we conducted a 10X Genomics single-nucleus transcriptome sequencing experiment on the ovaries of macaque monkeys after HA-MSC treatment. Methods The results of cell subgroup classification were visualized by 10X Genomics single nuclear transcriptome sequencing. The aging model of hGCs was established, and the migration ability of the cells was determined after coculture of HA-MSCs and aging hGCs. The genes screened by single nuclear transcriptional sequencing were verified in vitro by qPCR. Results Compared with the aging model group, the number of cell receptor pairs in each subgroup of the HA-MSC-treated group increased overall. Treatment with 200 μmol/L H2O2 for 48 h was used as the optimum condition for the induction of hGC senescence. After coculture of noncontact HA-MSCs with senescent hGCs, it was found that HA-MSCs can reverse the cell structure, proliferation ability, senescence condition, expression level of senescence-related genes, and expression level of key genes regulating the senescence pathway in normal hGCs. Conclusions HA-MSC therapy can improve the tissue structure and secretion function of the ovary through multiple cellular and molecular mechanisms to resist ovarian aging. In vitro validation experiments further supported the results of single-cell sequencing, which provides evidence supporting a new option for stem cell treatment of ovarian senescence.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), can induce a plethora of neurological complications in some patients. However, it is still under debate whether SARS-CoV-2 directly infects the brain or whether CNS sequelae result from systemic inflammatory responses triggered in the periphery. By using high-resolution microscopy, we investigated whether SARS-CoV-2 reaches the brain and how viral neurotropism can be modulated by aging in a non-human primate model of COVID-19. Seven days after infection, SARS-CoV-2 was detected in the olfactory cortex and interconnected regions and was accompanied by robust neuroinflammation and neuronal damage exacerbated in aged, diabetic animals. Our study provides an initial framework for identifying the molecular and cellular mechanisms underlying SARS-CoV-2 neurological complications, which will be essential to reducing both the short- and long-term burden of COVID-19.

Midget and parasol ganglion cells (GCs) represent the major output channels from the primate eye to the brain. On-type midget and parasol GCs exhibit a higher background spike rate and thus can respond more linearly to contrast changes than their Off-type counterparts. Here, we show that a calcium-permeable AMPA receptor (CP-AMPAR) antagonist blocks background spiking and sustained light-evoked firing in On-type GCs while preserving transient light responses. These effects are selective for On-GCs and are occluded by a gap-junction blocker suggesting involvement of AII amacrine cells (AII-ACs). Direct recordings from AII-ACs, cobalt uptake experiments, and analyses of transcriptomic data confirm that CP-AMPARs are expressed by primate AII-ACs. Overall, our data demonstrate that under some background light levels, CP-AMPARs at the rod bipolar to AII-AC synapse drive sustained signaling in On-type GCs and thus contribute to the more linear contrast signaling of the primate On- versus Off-pathway.

Non-human primates (NHPs) are pivotal animal models for translating novel cell replacement therapies into clinical applications, including validating the safety and efficacy of induced pluripotent stem cell (iPSC)-derived products. Preclinical development and the testing of cell-based therapies ideally comprise xenogeneic (human stem cells into NHPs) and allogenic (NHP stem cells into NHPs) transplantation studies. For the allogeneic approach, it is necessary to generate NHP-iPSCs with generally equivalent quality to the human counterparts that will be used later on in patients. Here, we report the generation and characterization of transgene- and feeder-free cynomolgus monkey (Macaca fascicularis) iPSCs (Cyno-iPSCs). These novel cell lines have been generated according to a previously developed protocol for the generation of rhesus macaque, baboon, and human iPSC lines. Beyond their generation, we demonstrate the potential of the novel Cyno-iPSCs to differentiate into two clinically relevant cell types, i.e., cardiomyocytes and neurons. Overall, we provide a resource of novel iPSCs from the most frequently used NHP species in the regulatory testing of biologics and classical pharmaceutics to expand our panel of iPSC lines from NHP species with high relevance in preclinical testing and translational research. [ABSTRACT FROM AUTHOR]

Simple Summary: Although alopecia is prevalent among captive rhesus macaques, its cause is not well understood. Poor coat quality may raise concerns because it can be a byproduct of conditions such as stress, autoimmune disease, hormonal imbalance, infection, or poor nutrition. Despite lack of consensus as to the cause(s) of alopecia, multiple studies in captive primates have found two commonalities: alopecia fluctuates seasonally, and pregnant females tend to have more alopecia than males or nonpregnant females. Most studies have focused on loss of hair, rather than if and when hair is regrown, but alopecia can result from disruption to any phase of the hair follicle's cycle of shedding and regrowth. To better understand how season and pregnancy affect the hair follicle cycle and alopecia, we documented the severity of alopecia and the presence of hair regrowth in outdoor group-housed rhesus for one year. We found a seasonal pattern of alopecia and regrowth in all animals, and that females in their third trimester showed less regrowth, which prevented a decrease in alopecia. Regrowth for females resumed on average 1–2 months postpartum. Hair shedding and regrowth follows a seasonal pattern in rhesus, and conditions in late-term pregnancy suppress hair regrowth into early postpartum. Several studies have examined the etiology of alopecia, or hair loss, in rhesus macaques. While outcomes differ across studies, some commonalities have emerged. Females, particularly pregnant females, show more alopecia than males, and alopecia follows a seasonal pattern. Much research has explored causes of hair loss; however, alopecia can result from lack of hair growth in addition to hair loss. To better understand how sex, reproductive state, and season affect alopecia, we followed 241 rhesus macaques (Macaca mulatta) in outdoor breeding groups over one year, recording both alopecia severity and presence of hair regrowth. We found that both alopecia and hair regrowth followed a seasonal pattern; alopecia was highest in spring and lowest in late summer, while regrowth started in spring and peaked in late summer. Reproductive state also correlated with both alopecia and hair growth. Females in their third trimester had the highest average level of alopecia and the lowest amount of hair regrowth. Regrowth resumed postpartum, regardless of whether females were rearing an infant. Results indicate that the seasonal pattern of alopecia is due in part to the seasonal limitations on hair regrowth, and that breeding, which also occurs seasonally in rhesus macaques, may further suppress hair regrowth. [ABSTRACT FROM AUTHOR]

A major goal of modern neuroscience is to understand the functions of the varied neuronal types that comprise the mammalian brain. Toward this end, some types of neurons can be targeted and manipulated with enhancer-bearing AAV vectors. These vectors hold great promise to advance basic and translational neuroscience, but to realize this potential, their selectivitymust be characterized. In this study, we investigated the selectivity of AAV vectors carrying an enhancer of the murine Dlx5 and Dlx6 genes. Vectors were injected into the visual cortex of two macaque monkeys, the frontal cortex of two others, and the somatosensory/motor cortex of three rats. Post-mortem immunostaining revealed that parvalbumin-expressing neurons were transduced efficiently in all cases but calretinin-expressing neurons were not. We speculate that this specificity is a consequence of differential activity of this DLX5/6 enhancer in adult neurons of different developmental lineages. [ABSTRACT FROM AUTHOR]

The ventrolateral prefrontal cortex (VLPFC) shows robust activation during the perception of faces and voices. However, little is known about what categorical features of social stimuli drive neural activity in this region. Since perception of identity and expression are critical social functions, we examined whether neural responses to naturalistic stimuli were driven by these two categorical features in the prefrontal cortex. We recorded single neurons in the VLPFC, while two male rhesus macaques (Macaca mulatta) viewed short audiovisual videos of unfamiliar conspecifics making expressions of aggressive, affiliative, and neutral valence. Of the 285 neurons responsive to the audiovisual stimuli, 111 neurons had a main effect (two-way ANOVA) of identity, expression, or their interaction in their stimulus-related firing rates; however, decoding of expression and identity using single-unit firing rates rendered poor accuracy. Interestingly, when decoding from pseudo-populations of recorded neurons, the accuracy for both expression and identity increased with population size, suggesting that the population transmitted information relevant to both variables. Principal components analysis of mean population activity across time revealed that population responses to the same identity followed similar trajectories in the response space, facilitating segregation from other identities. Our results suggest that identity is a critical feature of social stimuli that dictates the structure of population activity in the VLPFC, during the perception of vocalizations and their corresponding facial expressions. These findings enhance our understanding of the role of the VLPFC in social behavior. [ABSTRACT FROM AUTHOR]

During free viewing, faces attract gaze and induce specific fixation patterns corresponding to the facial features. This suggests that neurons encoding the facial features are in the causal chain that steers the eyes. However, there is no physiological evidence to support a mechanistic link between face-encoding neurons in high-level visual areas and the oculomotor system. In this study, we targeted the middle face patches of the inferior temporal (IT) cortex in two macaque monkeys using an functional magnetic resonance imaging (fMRI) localizer. We then utilized muscimol microinjection to unilaterally suppress IT neural activity inside and outside the face patches and recorded eye movements while the animals free viewing natural scenes. Inactivation of the face-selective neurons altered the pattern of eye movements on faces: The monkeys found faces in the scene but neglected the eye contralateral to the inactivation hemisphere. These findings reveal the causal contribution of the high-level visual cortex in eye movements. [ABSTRACT FROM AUTHOR]

The functional organization of the primate insula has been studied using a variety of techniques focussing on regional differences in either architecture, connectivity, or function. These complementary methods offered insights into the complex organization of the insula and proposed distinct parcellation schemes at varying levels of detail and complexity. The advent of imaging techniques that allow noninvasive assessment of structural and functional connectivity, has popularized data-driven connectivity-based parcellation methods to investigate the organization of the human insula. Yet, it remains unclear if the subdivisions derived from these data-driven clustering methods reflect meaningful descriptions of the functional specialization of the insula. In this study, we employed hierarchical clustering to examine the cluster parcellations of the macaque insula. As our aim was exploratory, we examined parcellations consisting of two up to ten clusters. Three different cluster validation methods (fingerprinting, silhouette, elbow) converged on a four-cluster solution as the most optimal representation of our data. Examining functional response properties of these clusters, in addition to their brain-wide functional connectivity suggested a functional specialization related to processing gustatory, somato-motor, vestibular and social visual cues. However, a more detailed functional differentiation aligning with previous functional investigations of insula subfields became evident at higher cluster numbers beyond the proposed optimal four clusters. Overall, our findings demonstrate that resting-state-based hierarchical clustering can provide a meaningful description of the insula's functional organization at some level of detail. Nonetheless, cluster parcellations derived from this method are best combined with data obtained through other modalities, to provide a more comprehensive and detailed account of the insula's complex functional organization. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that umbilical cord mesenchymal stem cells have an anti-aging effect in ovaries, but the cellular and molecular mechanisms of HA-MSC ovarian anti-aging remain to be studied. Therefore, we conducted a 10X Genomics single-nucleus transcriptome sequencing experiment on the ovaries of macaque monkeys after HA-MSC treatment. Methods: The results of cell subgroup classification were visualized by 10X Genomics single nuclear transcriptome sequencing. The aging model of hGCs was established, and the migration ability of the cells was determined after coculture of HA-MSCs and aging hGCs. The genes screened by single nuclear transcriptional sequencing were verified in vitro by qPCR. Results: Compared with the aging model group, the number of cell receptor pairs in each subgroup of the HA-MSC-treated group increased overall. Treatment with 200 μmol/L H2O2 for 48 h was used as the optimum condition for the induction of hGC senescence. After coculture of noncontact HA-MSCs with senescent hGCs, it was found that HA-MSCs can reverse the cell structure, proliferation ability, senescence condition, expression level of senescence-related genes, and expression level of key genes regulating the senescence pathway in normal hGCs. Conclusions: HA-MSC therapy can improve the tissue structure and secretion function of the ovary through multiple cellular and molecular mechanisms to resist ovarian aging. In vitro validation experiments further supported the results of single-cell sequencing, which provides evidence supporting a new option for stem cell treatment of ovarian senescence. [ABSTRACT FROM AUTHOR]

Primates rely on two eyes to perceive depth, while maintaining stable vision when either one eye or both eyes are open. Although psychophysical and modeling studies have investigated how monocular signals are combined to form binocular vision, the underlying neuronal mechanisms, particularly in V1 where most neurons exhibit binocularity with varying eye preferences, remain poorly understood. Here, we used two-photon calcium imaging to compare the monocular and binocular responses of thousands of simultaneously recorded V1 superficial-layer neurons in three awake macaques. During monocular stimulation, neurons preferring the stimulated eye exhibited significantly stronger responses compared to those preferring both eyes. However, during binocular stimulation, the responses of neurons preferring either eye were suppressed on the average, while those preferring both eyes were enhanced, resulting in similar neuronal responses irrespective of their eye preferences, and an overall response level similar to that with monocular viewing. A neuronally realistic model of binocular combination, which incorporates ocular dominance-dependent divisive interocular inhibition and binocular summation, is proposed to account for these findings.

Late adolescence is a period of dynamic change in the brain as humans learn to navigate increasingly complex environments. In particular, prefrontal cortical (PFC) regions undergo extensive remodeling as the brain is fine-tuned to orchestrate cognitive control over attention, reasoning, and emotions. Late adolescence also presents a uniquely vulnerable period as neurodevelopmental illnesses, such as schizophrenia, become evident and worsen into young adulthood. Challenges in early development, including prenatal exposure to infection, may set the stage for a cascade of maladaptive events that ultimately result in aberrant PFC connectivity and function before symptoms emerge. A growing body of research suggests that activation of the mother's immune system during pregnancy may act as a disease primer, in combination with other environmental and genetic factors, contributing to an increased risk of neurodevelopmental disorders, including schizophrenia. Animal models provide an invaluable opportunity to examine the course of brain and behavioral changes in offspring exposed to maternal immune activation (MIA). Although the vast majority of MIA research has been carried out in rodents, here we highlight the translational utility of the nonhuman primate (NHP) as a model species more closely related to humans in PFC structure and function. In this review, we consider the protracted period of brain and behavioral maturation in the NHP, describe emerging findings from MIA NHP offspring in the context of rodent preclinical models, and lastly explore the translational relevance of the NHP MIA model to expand understanding of the etiology and developmental course of PFC pathology in schizophrenia.

Primate cerebral cortex is highly convoluted with much of the cortical surface buried in sulcal folds. The origins of cortical folding and its functional relevance have been a major focus of systems and cognitive neuroscience, especially when considering stereotyped patterns of cortical folding that are shared across individuals within a primate species and across multiple species. However, foundational questions regarding organizing principles shared across species remain unanswered. Taking a cross-species comparative approach with a careful consideration of historical observations, we investigate cortical folding relative to primary visual cortex (area V1). We identify two macroanatomical structures-the retrocalcarine and external calcarine sulci-in 24 humans and 6 macaque monkeys. We show that within species, these sulci are identifiable in all individuals, fall on a similar part of the V1 retinotopic map, and thus, serve as anatomical landmarks predictive of functional organization. Yet, across species, the underlying eccentricity representations corresponding to these macroanatomical structures differ strikingly across humans and macaques. Thus, the correspondence between retinotopic representation and cortical folding for an evolutionarily old structure like V1 is species-specific and suggests potential differences in developmental and experiential constraints across primates.

Introduction: It is becoming clearer that the microbiota helps drive responses to vaccines; however, little is known about the underlying mechanism. In this study, we aimed to identify microbial features that are associated with vaccine immunogenicity in infant rhesus macaques. Methods: We analyzed 16S rRNA gene sequencing data of 215 fecal samples collected at multiple timepoints from 64 nursery-reared infant macaques that received various HIV vaccine regimens. PERMANOVA tests were performed to determine factors affecting composition of the gut microbiota throughout the first eight months of life in these monkeys. We used DESeq2 to identify differentially abundant bacterial taxa, PICRUSt2 to impute metagenomic information, and mass spectrophotometry to determine levels of fecal shortchain fatty acids and bile acids. Results: Composition of the early-life gut microbial communities in nurseryreared rhesus macaques from the same animal care facility was driven by age, birth year, and vaccination status. We identified a Sutterella and a Rodentibacter species that positively correlated with vaccine-elicited antibody responses, with the Sutterella species exhibiting more robust findings. Analysis of Sutterellarelated metagenomic data revealed five metabolic pathways that significantly correlated with improved antibody responses following HIV vaccination. Given these pathways have been associated with short-chain fatty acids and bile acids, we quantified the fecal concentration of these metabolites and found several that correlated with higher levels of HIV immunogen-elicited plasma IgG. Discussion: Our findings highlight an intricate bidirectional relationship between the microbiota and vaccines, where multiple aspects of the vaccination regimen modulate the microbiota and specific microbial features facilitate vaccine responses. An improved understanding of this microbiota-vaccine interplay will help develop more effective vaccines, particularly those that are tailored for early life. [ABSTRACT FROM AUTHOR]

Macaque species play important roles in the cultures, and religions of many societies. They are an essential component of tropical biodiversity, contributing to forest regeneration and ecosystem health. The close phylogenetic relationship between humans and Macaque species also creates a high potential for pathogen exchange. A total of 228 Macaques which belong to four species, including Macaca arctoides, Macaca leonine, Macaca assamensis, and Macaca mulatta, were rescued in the Center Rescue, Conservation and Creature Development, Phong Nha-Ke Bang National Park (PN-KB NP). Of 228 Macaques, 149 (65.4%) individuals successfully reintegrated into the wild. The prevalence and the antimicrobial resistance (AMR) profile of Escherichia coli (E. coli), Salmonella, and Staphylococcus aureus (S. aureus) isolates from Macaques rescuing in the Center were investigated. The fecal and nasal samples from 19 Macaques were collected. These samples were positive for E. coli (73,7%), Salmonella (36.8%), and S. aureus (57.9%). All of the tested bacterial strains showed 100% resistance to penicillin and vancomycin. The multi-drug resistant (MDR) profile was observed in S. aureus (71,4%), E. coli (95,3%), and Salmonella (100%). This is the first report on the rescue and natural reintegration of the Macaque species status in Vietnam and the prevalence of AMR in zoonotic bacterial pathogens isolated from these Macaques. This result indicated that AMR of the zoonotic bacterial pathogens could colonize in Macaques and may transmit to humans. [ABSTRACT FROM AUTHOR]

Macaques, which belong to non-human primates, due to their similarity to humans, are used in scientific research, as animals for human entertainment, and also as animals through which financial profits can be generated. Filming macaques has become a source of income, thanks to the possibility of presenting films on the Internet. This contemporary form of agora gave the opportunity to reach numerous recipients around the world. In this way, macaques became victims: through their physical and emotional-behavioral similarities, they became grateful actors. They can be “humanized” even more by putting on clothes or forcing them to behave more like humans. This is a source of suffering for macaques: they are intelligent, emotional and social animals, whose human desire to earn money devoids of the opportunity to live a normal life in harmony with their nature. This is simply an abuse. In this article, I present an introductory socio-emotional specificity of these animals and an outline of the issue of exploiting macaques on the Internet. [ABSTRACT FROM AUTHOR]

Integrating multisensory inputs to generate accurate perception and guide behavior is among the most critical functions of the brain. Subcortical regions such as the amygdala are involved in sensory processing including vision and audition, yet their roles in multisensory integration remain unclear. In this study, we systematically investigated the function of neurons in the amygdala and adjacent regions in integrating audiovisual sensory inputs using a semi-chronic multi-electrode array and multiple combinations of audiovisual stimuli. From a sample of 332 neurons, we showed the diverse response patterns to audiovisual stimuli and the neural characteristics of bimodal over unimodal modulation, which could be classified into four types with differentiated regional origins. Using the hierarchical clustering method, neurons were further clustered into five groups and associated with different integrating functions and sub-regions. Finally, regions distinguishing congruent and incongruent bimodal sensory inputs were identified. Overall, visual processing dominates audiovisual integration in the amygdala and adjacent regions. Our findings shed new light on the neural mechanisms of multisensory integration in the primate brain. [ABSTRACT FROM AUTHOR]

To probe the presence of mirror neurons in the human brain, cross-modal fMRI adaptation has been suggested as a suitable technique. The rationale behind this suggestion is that this technique allows making more accurate inferences about neural response properties underlying fMRI voxel activations, beyond merely showing shared voxels that are active during both action observation and execution. However, the validity of using cross-modal fMRI adaptation to demonstrate the presence of mirror neurons in parietal and premotor brain regions has been questioned given the inconsistent and weak results obtained in human studies. A better understanding of cross-modal fMRI adaptation effects in the macaque brain is required as the rationale for using this approach is based on several assumptions related to macaque mirror neuron response properties that still need validation. Here, we conducted a cross-modal fMRI adaptation study in macaque monkeys, using the same action execution and action observation tasks that successfully yielded mirror neuron region cross-modal action decoding in a previous monkey MVPA study. We scanned two male rhesus monkeys while they first executed a sequence of either reach-and-grasp or reach-and-touch hand actions and then observed a video of a human actor performing these motor acts. Both whole-brain and region-of-interest analyses failed to demonstrate cross-modal fMRI adaptation effects in parietal and premotor mirror neuron regions. Our results, in line with previous findings in non-human primates, show that cross-modal motor-to-visual fMRI adaptation is not easily detected in monkey brain regions known to house mirror neurons. Thus, our results advocate caution in using cross-modal fMRI adaptation as a method to infer whether mirror neurons can be found in the primate brain. [ABSTRACT FROM AUTHOR]

Aged rhesus monkeys, like aged humans, show declines in cognitive function. We present cognitive test data from a large sample of male and female rhesus monkeys, 34 young (aged 3.5–13.6 years) and 71 aged (aged 19.9–32.5 years at the start of cognitive testing). Monkeys were tested on spatiotemporal working memory (delayed response), visual recognition memory (delayed nonmatching to sample), and stimulus-reward association learning (object discrimination), tasks with an extensive evidence base in nonhuman primate neuropsychology. On average, aged monkeys performed worse than young on all 3 tasks. Acquisition of delayed response and delayed nonmatching to sample was more variable in aged monkeys than in young. Performance scores on delayed nonmatching to sample and object discrimination were associated with each other, but neither was associated with performance on delayed response. Sex and chronological age were not reliable predictors of individual differences in cognitive outcome among the aged monkeys. These data establish population norms for multiple cognitive tests in young and aged rhesus monkeys in the largest sample reported to date. They also illustrate independence of cognitive aging in task domains dependent on the prefrontal cortex and medial temporal lobe. [ABSTRACT FROM AUTHOR]

Introduction: Current approaches for treating sporadic Alzheimer's disease (sAD) focus on removal of amyloid beta 1‐42 (Aβ1‐42) or phosphorylated tau, but additional strategies are needed to reduce neuropathology at earlier stages prior to neuronal damage. Longstanding data show that calcium dysregulation is a key etiological factor in sAD, and the cortical neurons most vulnerable to tau pathology show magnified calcium signaling, for example in dorsolateral prefrontal cortex (dlPFC) and entorhinal cortex (ERC). In primate dlPFC and ERC, type 3 metabotropic glutamate receptors (mGluR3s) are predominately post‐synaptic, on spines, where they regulate cAMP‐calcium signaling, a process eroded by inflammatory glutamate carboxypeptidase II (GCPII) actions. The current study tested whether enhancing mGluR3 regulation of calcium via chronic inhibition of GCPII would reduce tau hyperphosphorylation in aged macaques with naturally‐occurring tau pathology. Methods: Aged rhesus macaques were treated daily with the GCPII inhibitor, 2‐MPPA (2‐3‐mercaptopropyl‐penanedioic acid (2‐MPPA)), Aged rhesus macaques were treated daily with the GCPII inhibitor, 2‐MPPA (2‐3‐mercaptopropyl‐penanedioic acid (2‐MPPA)), Results: Aged macaques that received 2‐MPPA had significantly lower pT217Tau levels in dlPFC and ERC, and had lowered plasma pT217Tau levels from baseline. pT217Tau levels correlated significantly with GCPII activity in dlPFC. Both 2‐MPPA‐ and vehicle‐treated monkeys showed cognitive improvement; 2‐MPPA had no apparent side effects. Exploratory CSF analyses indicated reduced pS202Tau with 2‐MPPA administration, confirmed in dlPFC samples. Discussion: These data provide proof‐of‐concept support that GCPII inhibition can reduce tau hyperphosphorylation in the primate cortices most vulnerable in sAD. GCPII inhibition may be particularly helpful in reducing the risk of sAD caused by inflammation. These data in nonhuman primates should encourage future research on this promising mechanism. Highlights: Inflammation is a key driver of sporadic Alzheimer's disease.GCPII inflammatory signaling in brain decreases mGluR3 regulation of calcium.Chronic inhibition of GCPII inflammatory signaling reduced pT217Tau in aged monkeys.GCPII inhibition is a novel strategy to help prevent tau pathology at early stages. [ABSTRACT FROM AUTHOR]

A major goal of modern neuroscience is to understand the functions of the varied neuronal types that comprise the mammalian brain. Toward this end, some types of neurons can be targeted and manipulated with enhancer-bearing AAV vectors. These vectors hold great promise to advance basic and translational neuroscience, but to realize this potential, their selectivity must be characterized. In this study, we investigated the selectivity of AAV vectors carrying an enhancer of the murine Dlx5 and Dlx6 genes. Vectors were injected into the visual cortex of two macaque monkeys, the frontal cortex of two others, and the somatosensory/motor cortex of three rats. Post-mortem immunostaining revealed that parvalbumin-expressing neurons were transduced efficiently in all cases but calretinin-expressing neurons were not. We speculate that this specificity is a consequence of differential activity of this DLX5/6 enhancer in adult neurons of different developmental lineages.

The functional organization of the primate insula has been studied using a variety of techniques focussing on regional differences in either architecture, connectivity, or function. These complementary methods offered insights into the complex organization of the insula and proposed distinct parcellation schemes at varying levels of detail and complexity. The advent of imaging techniques that allow non-invasive assessment of structural and functional connectivity, has popularized data-driven connectivity-based parcellation methods to investigate the organization of the human insula. Yet, it remains unclear if the subdivisions derived from these data-driven clustering methods reflect meaningful descriptions of the functional specialization of the insula. In this study, we employed hierarchical clustering to examine the cluster parcellations of the macaque insula. As our aim was exploratory, we examined parcellations consisting of two up to ten clusters. Three different cluster validation methods (fingerprinting, silhouette, elbow) converged on a four-cluster solution as the most optimal representation of our data. Examining functional response properties of these clusters, in addition to their brain-wide functional connectivity suggested a functional specialization related to processing gustatory, somato-motor, vestibular and social visual cues. However, a more detailed functional differentiation aligning with previous functional investigations of insula subfields became evident at higher cluster numbers beyond the proposed optimal four clusters. Overall, our findings demonstrate that resting-state-based hierarchical clustering can provide a meaningful description of the insula’s functional organization at some level of detail. Nonetheless, cluster parcellations derived from this method are best combined with data obtained through other modalities, to provide a more comprehensive and detailed account of the insula’s complex functional organization.

Abstract Spinal cord injury (SCI) animal models have been widely created and utilized for repair therapy research, but more suitable experimental animals and accurate modeling methodologies are required to achieve the desired results. In this experiment, we constructed an innovative dorsal 1/4 spinal cord transection macaque model that had fewer severe problems, facilitating postoperative care and recovery. In essence, given that monkeys and humans share similar genetics and physiology, the efficacy of this strategy in a nonhuman primate SCI model basically serves as a good basis for its prospective therapeutic use in human SCI.

The increasing overlap of resources between human and long-tailed macaque (Macaca fascicularis) (LTM) populations have escalated human–primate conflict. In Malaysia, LTMs are labeled as a ‘pest’ species due to the macaques’ opportunistic nature. This study investigates the activity budget of LTMs in an urban tourism site and how human activities influence it. Observational data were collected from LTMs daily for a period of four months. The observed behaviors were compared across differing levels of human interaction, between different times of day, and between high, medium, and low human traffic zones. LTMs exhibited varying ecological behavior patterns when observed across zones of differing human traffic, e.g., higher inactivity when human presence is high. More concerning is the impact on these animals’ welfare and group dynamics as the increase in interactions with humans takes place; we noted increased inactivity and reduced intra-group interaction. This study highlights the connection that LTMs make between human activity and sources of anthropogenic food. Only through understanding LTM interaction can the cause for human–primate conflict be better understood, and thus, more sustainable mitigation strategies can be generated.

Briefly discusses causes the issue of unfavourable interactions between people and free-living human-nonhuman primates, and alternatives to lethal methods of resolving these.