Chimpanzees Research Articles

Abstract 6310: Phylogenetic conservation of primate Trop-2 underscores favorable pharmacokinetics and lack of toxicity of the cancer-selective Hu2G10 anti-Trop-2

Abstract Trop-2 is a transmembrane signal transducer that activates growth-signaling networks that converge on Akt, ERK, Cyclin D1, NFkB (1). We discovered that Trop-2 cleavage by ADAM10 is an activator switch of cancer growth and metastatic diffusion (2) and exposes novel target epitopes that are inaccessible in the unprocessed wtTrop-2. The Hu2G10 mAb selectively binds these epitopes with an affinity that is ≈10,000-fold higher than for the unprocessed molecule. To validate a reliable model for Hu2G10 binding in vivo, we explored Trop-2 phylogenetic conservation in primates. Pan troglodites (chimpanzee), Papio anubis (baboon), Macaca mulatta/fascicularis (Rhesus/Cynomolgous), Callithrix jaccus (marmoset) TROP2/TACSTD2 sequences were compared. The only difference between Pan troglodytes and human Trop-2 is one additional leucine in the Pan leader peptide, making the mature Trop-2 identical to that in man. The Macaca mulatta/fascicularis Trop-2 sequences are 97% identical, 100% similar to the human sequence. Three-dimensional modeling revealed polymorphic residues usage versus activation-driven structural rearrangement of Trop-2. COS-7 and HEK-293 cells transfected with individual primate Trop-2 showed efficient recognition by Hu2G10 in all tested species. Immunohistochemistry analysis of normal Macaca tissues showed Trop-2 expression patterns essentially corresponding to the human ones. IV injected Hu2G10 at doses of 5 to 10 mg/kg was well tolerated by Cynomolgous monkeys. No neurological, respiratory, digestive and urinary adverse effects were observed, and no body-weight loss occurred during the 28-day observation. No alterations of blood monocyte, neutrophil and basophil counts nor significant changes in biochemical parameters were detected. A pharmacokinetic (PK), study was carried out. Serum concentration of Hu2G10 was determined using anti-idiotypic antibody-based ELISA assays. At the higher dosing of 10 mg/kg Hu2G10 serum values reached a peak 2-hour after the injection (13281±4686 ng/ml). The concentration of Hu2G10 then diminished gradually, and reached baseline levels on day 21. The serum concentration peak of 5 mg/kg Hu2G10 was 5759±1729 ng/ml, and reached baseline levels on day 14. Thus, Hu2G10 is stable in plasma, and is detectable in the circulation up to three weeks after the infusion (t1/2=6.5 days). Taken together, these findings validate primate models as reliable for assessing Hu2G10 in vivo toxicity and PK. The lack of toxicity and favorable PK parameters candidate the cancer specific Hu2G10 as first-in-class anti-Trop-2 mAb. (1) Guerra E. et al., Oncogene 41:1795-1808 (2022).(2) Trerotola M. et al., Neoplasia 23: 415-428 (2021). Citation Format: Saverio Alberti, Martina Ceci, Ludovica Pantalone, Marco Trerotola, Emanuela Guerra. Phylogenetic conservation of primate Trop-2 underscores favorable pharmacokinetics and lack of toxicity of the cancer-selective Hu2G10 anti-Trop-2. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6310.

The evolution of the adolescent growth spurt: Urinary biomarkers of bone turnover in wild chimpanzees (Pan troglodytes)

Life history theory addresses how organisms balance development and reproduction. Mammals usually invest considerable energy into growth in infancy, and they do so incrementally less until reaching adult body size, when they shift energy to reproduction. Humans are unusual in having a long adolescence when energy is invested in both reproduction and growth, including rapid skeletal growth around puberty. Although many primates, especially in captivity, experience accelerated growth in mass around puberty, it remains unclear whether this represents skeletal growth. Without data on skeletal growth in nonhuman primates, anthropologists have often assumed the adolescent growth spurt is uniquely human, and hypotheses for its evolution have focused on other uniquely human traits. The lack of data is largely due to methodological difficulties of assessing skeletal growth in wild primates. Here, we use two urinary markers of bone turnover-osteocalcin and collagen-to study skeletal growth in a large, cross-sectional sample of wild chimpanzees (Pan troglodytes) at Ngogo, Kibale National Park, Uganda. For both bone turnover markers, we found a nonlinear effect of age, which was largely driven by males. For male chimpanzees, values for osteocalcin and collagen peaked at age 9.4 years and 10.8 years, respectively, which corresponds to early and middle adolescence. Notably, collagen values increased from 4.5 to 9 years, suggesting faster growth during early adolescence compared to late infancy. Biomarker levels plateaued at 20 years in both sexes, suggesting skeletal growth continues until then. Additional data, notably on females and infants of both sexes, are needed, as are longitudinal samples. However, our cross-sectional analysis suggests an adolescent growth spurt in the skeleton of chimpanzees, especially for males. Biologists should avoid claiming that the adolescent growth spurt is uniquely human, and hypotheses for the patterns of human growth should consider variation in our primate relatives.

EVALUATION OF OSCILLOMETRIC BLOOD PRESSURE MEASUREMENT USING A FINGER CUFF IN ANESTHETIZED CHIMPANZEES (PAN TROGLODYTES).

Cardiovascular disease is common among chimpanzees (Pan troglodytes), and serial blood pressure monitoring in conscious animals may improve disease surveillance and guide hypertension treatment strategies. The objective of this study was to compare the accuracy of a noninvasive, oscillometric blood pressure monitor using a finger blood pressure cuff with invasively measured blood pressure in anesthetized chimpanzees. Twelve chimpanzees were anesthetized with tiletamine-zolazepam intramuscularly, intubated, and maintained on inhaled isoflurane to effect. Blood pressure measurements, which included systolic arterial pressure (SAP), mean arterial pressure (MAP), and diastolic arterial pressure (DAP), were collected simultaneously from an oscillometric blood pressure cuff placed on a forelimb digit (FBP) and a direct arterial catheter (IBP) every 5-10 min while anesthetized. One hundred paired samples were collected, and results were compared using Bland-Altman plots and analysis. FBP showed good agreement with IBP for SAP, MAP, and DAP but consistently overestimated values compared with IBP. FBP may be useful for serial blood pressure monitoring in conscious chimpanzees.

Carpal kinematics and morphological correlates of wrist ulnar deviation mobility in nonhuman anthropoid primates.

Primates employ wrist ulnar deviation during a variety of locomotor and manipulative behaviors. Extant hominoids share a derived condition in which the ulnar styloid process has limited articulation or is completely separated from the proximal carpals, which is often hypothesized to increase ulnar deviation range of motion. Acute angulation of the hamate's triquetral facet is also hypothesized to facilitate ulnar deviation mobility and mechanics. In this study, we test these longstanding ideas. Three-dimensional (3D) carpal kinematics were examined using a cadaveric sample of Pan troglodytes, Pongo sp., and five monkey species. Ulnar styloid projection and orientation of the hamate's triquetral facet were quantified using 3D models. Although carpal rotation patterns in Pan and Pongo were uniquely similar in some respects, P. troglodytes exhibited overall kinematic similarity with large terrestrial cercopithecoids (Papio and Mandrillus). Pongo, Macaca, and Ateles had high wrist ulnar deviation ranges of motion, but Pongo did this via a unique mechanism. In Pongo, the triquetrum functions as a distal carpal rather than part of the proximal row. Ulnar styloid projection and wrist ulnar deviation range of motion were not correlated but ulnar deviation range of motion and the triquetrohamate facet orientation were correlated. Increased ulnar deviation mobility is not the function of ulnar styloid withdrawal in hominoids. Instead, this feature probably reduces stress on the ulnar side wrist or is a byproduct of adaptations that increase supination. Orientation of the hamate's triquetral facet offers some potential to reconstruct ulnar deviation mobility in extinct primates.

How Sanctuary Chimpanzees (Pan troglodytes) Use Space after Being Introduced to a Large Outdoor Habitat.

Wild chimpanzees live in large, mixed-sex groups that display a fission-fusion social organization. To provide a social environment more like that of wild chimpanzees, Chimp Haven integrated smaller groups of 3-4 individuals into one large group of 18 individuals. This large group was introduced to a 20,234.28 m2 forested habitat and associated indoor areas. This space was designed to allow the individual chimpanzees to choose their proximity to social companions and provide the group with a more natural environment in which they could express more species-typical behavior. The study took place over a 7-month period that began two weeks prior to the first groups being integrated and ended 4 months after the chimpanzees were released into the habitat. We collected data on the chimpanzees' arboreal, terrestrial, indoor, and outdoor spatial use. The chimpanzees' proximity to their nearest neighbor was also recorded, noting whether they were touching or within arm's reach. Data were collected during daytime and nighttime hours and were utilized to make management decisions about potential group formations. We examined the data using generalized linear mixed models (GLMMs) with individual subjects as a random factor and months as a repeated measure for location and proximity results. There were significant differences in the use of arboreal and outside space over the 7-month time frame, with females more likely to use the arboreal space than males. The chimpanzees were more likely to utilize the habitat over time and increased their proximity to group mates. The results of this study indicate that the chimpanzees responded positively to living in large groups in a spacious naturalistic environment.

Face to face interactions in chimpanzee (Pan troglodytes) and human (Homo sapiens) mother-infant dyads.

Human mothers interact with their infants in different ways. In Western, educated, industrialized, rich and democratic (WEIRD) societies, face-to-face interactions and mutual gazes are especially frequent, yet little is known about their developmental trajectories and if they differ from those of other primates. Using a cross-species developmental approach, we compared mother-infant interactions in 10 dyads of urban humans from a WEIRD society (Homo sapiens) and 10 dyads of captive zoo-based chimpanzees (Pan troglodytes), when infants were one, six and 12 months old. Results showed that face-to-face interactions with mutual gaze events were common in both groups throughout the infant's first year of life. The developmental trajectories of maternal and infants' looks partially differed between species, but mutual gaze events were overall longer in humans than in chimpanzees. Mutual gazes were also more frequent in humans, peaking at six months in humans, while increasing with age in chimpanzees. The duration and frequency of mutual gazes varied across contexts in both groups, with mutual gazes being longer during caring/grooming and feeding contexts. These findings confirm that some aspects of early socio-cognitive development are shared by humans and other primates, and highlight the importance of combining developmental and cross-species approaches to better understand the evolutionary roots of parenting behaviour. This article is part of a discussion meeting issue 'Face2face: advancing the science of social interaction'.

Factors affecting nest height and ground nesting behaviour in Eastern chimpanzees (Pan troglodytes schweinfurthii) of the northern Democratic Republic of the Congo.

In order to achieve a better understanding of the factors that might have led our hominin ancestors to transition to a more terrestrial niche, including sleeping on the ground, we have conducted a study on the ground nesting behavior of chimpanzees (Pan troglodytes). Chimpanzees, like all other species of great apes, build nests in which to sleep each night, but little is known about regional differences in their nesting habits. Previously, nesting on the ground was considered typical of gorillas, but rare in most populations of chimpanzees. Using data acquired during our extensive chimpanzee nesting survey conducted between 2004 and 2013 across a > 50 000km2 region in northern Democratic Republic of the Congo, we report a distinctive ground nesting behaviour of eastern chimpanzees (P. t. schweinfurthii). We have mapped the geographical distribution of ground nesting and compared its frequency at 20 survey areas on both sides of a large river, the Uele. We found that ground nests made up more than 1% of total nests at 15 of the 20 survey regions. For a subset of 16 of these regions, we utilized statistical models to investigate whether forest type and structure, as well as the abundance of carnivores and large herbivores, and the activities of humans impacted the frequency of ground nesting and nest height. We predicted that higher encounter rates of human and dangerous animal signs would be associated with lower rates of ground nesting as well as increased nest height. Overall, 10.4% of the Bili-Uéré chimpanzee nests were terrestrial, but the frequency of ground nesting varied extensively between the survey areas (0-29% of nests). The occurrence of ground nests was positively associated with denser forests (p= 0.004), herb patches (p < 0.001), and light gaps (p < 0.001). Light gaps (p < 0.001), herb patches (p= 0.044), and vine tangles (p= 0.016) also had a strong negative effect on nest height. Hunting by humans had a negative effect on the probability of the occurrence of ground nests (p= 0.001) and a positive one on nest height (p= 0.013), with a similar but likely marginal effect of large herbivores on nest height (p= 0.023). In addition, the chimpanzees nested at significantly lower heights with increasing distance from roads and settlements (p< 0.001). Carnivore encounter rates, however, had no significant impact on ground nest frequency or nest height. Our results indicate that ground nesting can no longer be considered a rare and patchily-occurring phenomenon in Pan troglodytes, but is instead a major component of the chimpanzee behavioural repertoire across a considerable fraction of the range of the Eastern subspecies. Our study highlights that neither the large body size of gorillas nor the taming of fire are necessary conditions for hominids to sleep overnight on the ground, even in areas inhabited by multiple species of large carnivore. Human hunting, however, appears to reduce the probability of ground nesting, or eliminate the behavior altogether.

The ear of the Sima de los Huesos hominins (Atapuerca, Spain).

Previous studies on the morphology of the inner ear (semicircular canals and cochlea) in the Sima de los Huesos hominin sample have provided important results on the evolution of these structures in the Neandertal lineage. Similarly, studies of the anatomy of the external and middle ear cavities of the Sima de los Huesos hominins have also provided important data on the auditory capacities of this European Middle Pleistocene population. The present contribution provides unpublished data on three new middle ear variables from the Sima de los Huesos fossils and compares these data with values from samples of Pan troglodytes, Homo neanderthalensis and Homo sapiens. The results of this analysis are combined with those obtained in previous studies to characterize the anatomy of the outer, middle and inner ear in the Sima de los Huesos fossils, as well as to establish the order of appearance of the features that characterize Neandertal ears. As in other cranial structures, the ear region in the Sima de los Huesos show a mosaic evolutionary pattern that includes primitive traits, others shared exclusively with Neandertals, and others that are specific to the Sima de los Huesos hominins. Neandertals and Sima de los Huesos hominins share two exclusive features of the middle ear that are among the first characteristics of the Neandertal lineage: a long tympanic cavity and a large entrance and exit of the mastoid antrum. Along with these traits, the Sima de los Huesos hominins present two specialized features: large volumes of the tympanic cavity and the mastoid antrum. Finally, the middle ear of the Neandertals is characterized by the presence of small angles between the tympanic axis and the plane of the oval window.

Age differences in cortical thickness and their association with cognition in chimpanzee (Pan troglodytes)

Humans and chimpanzees are genetically similar and share a number of life history, behavioral, cognitive and neuroanatomical similarities. Notwithstanding, our understanding of age-related changes in cognitive and motor functions in chimpanzees remains largely unstudied despite recent evident demonstrating that chimpanzees exhibit many of the same neuropathological features of Alzheimer's disease observed in human postmortem brains. Here, we examined age-related differences in cognition and cortical thickness measured from magnetic resonance images in a sample of 215 chimpanzees ranging in age between 9 and 54 years. We found that chimpanzees showed global and region-specific thinning of cortex with increasing age. Further, within the elderly cohort, chimpanzees that performed better than average had thicker cortex in frontal, temporal and parietal regions compared to chimpanzees that performed worse than average. Independent of age, we also found sex differences in cortical thickness in 4 brain regions. Males had higher adjusted cortical thickness scores for the caudal anterior cingulate, rostral anterior cingulate, and medial orbital frontal while females had higher values for the inferior parietal cortex. We found no evidence that increasing age nor sex was associated with asymmetries in cortical thickness. Moreover, age-related differences in cognitive function were only weakly associated with asymmetries in cortical thickness. In summary, as has been reported in humans and other primates, elderly chimpanzees show thinner cortex and variation in cortical thickness is associated with general cognitive functions.

Locomotion as a Measure of Well-Being in Captive Chimpanzees (Pan troglodytes).

Locomotion in non-human primates, including walking, climbing, and brachiating among other types of movement (but not pacing), is a species-typical behavior that varies with age, social housing conditions, and environmental factors (e.g., season, food availability, physical housing conditions). Given that captive primates are typically observed to engage in lower levels of locomotor behaviors than their wild counterparts, increases in locomotion are generally considered to be indicative of improved welfare in captivity. However, increases in locomotion do not always occur with improvements in welfare, and sometimes occur under conditions of negative arousal. The use of time spent in locomotion as a welfare indicator in studies of well-being is relatively limited. We conducted focal animal observations on 120 captive chimpanzees across a series of studies and found higher percentages of time spent in locomotion (1) upon transfer to a new enclosure type, (2) in larger groups with wider within-group age ranges, and fewer males, and (3) with participation in an experimental medication choice paradigm. We also found that, among geriatric chimpanzees, those housed in nongeriatric groups exhibited more locomotion than those living in geriatric groups. Lastly, locomotion was significantly negatively correlated with several indicators of poor welfare and significantly positively correlated with behavioral diversity, one indicator of positive welfare. Overall, the increases in time spent in locomotion observed in these studies were part of an overall behavioral pattern indicative of enhanced welfare, suggesting that an increase in time spent in locomotion itself may be an indicator of enhanced welfare. As such, we suggest that levels of locomotion, which are typically assessed in most behavioral experiments, may be used more explicitly as indicators of welfare in chimpanzees.

Variability in molar crown morphology and cusp wear in two Western chimpanzee populations.

Chimpanzees (Pan troglodytes) possess a relatively generalized molar morphology allowing them to access a wide range of foods. Comparisons of crown and cusp morphology among the four subspecies have suggested relatively large intraspecific variability. Here, we compare molar crown traits and cusp wear of two geographically close populations of Western chimpanzees, P. t. verus, to provide further information on intraspecific dental variability. Micro-CT reconstructions of high-resolution replicas of first and second molars of two Western chimpanzee populations from Ivory Coast (Taï National Park) and Liberia, respectively were used for this study. First, we analyzed projected tooth and cusp 2D areas as well as the occurrence of cusp six (C6) on lower molars. Second, we quantified the molar cusp wear three-dimensionally to infer how the individual cusps alter with advancing wear. Both populations are similar in their molar crown morphology, except for a higher appearance rate of a C6 in Taï chimpanzees. In Taï chimpanzees, lingual cusps of upper molars and buccal cusps of lower molars possess an advanced wear pattern compared to the remaining cusps, while in Liberian chimpanzees this wear gradient is less pronounced. The similar crown morphology between both populations fits with previous descriptions for Western chimpanzees and provides additional data on dental variation within this subspecies. The wear pattern of the Taï chimpanzees are in concordance with their observed tool rather than tooth use to open nuts/seeds, while the Liberian chimpanzees may have consumed hard food items crushed between their molars.

Tool assisted task on touchscreen: a case study on drawing behaviour in chimpanzees (Pan troglodytes)

Abstract Observations of drawing behaviour in chimpanzees have often focused on the completed drawings. Here, we compared drawing behaviour using fingers or tools on a touch-sensitive monitor between five chimpanzees from the Kumamoto Sanctuary (KS) and two from the Primate Research Institute (PRI), both located at Kyoto University, Japan. Regarding drawing duration, both PRI females drew relatively longer than the other, with the exception of one KS female. However, a long drawing duration did not correspond with a decrease in the number of pauses, which can be interpreted as a lack of concentration or interest. Therefore, to better understand the engagement of individuals, we recorded the time spent looking at the touchscreen. Pan, one of the two PRI females, had the longest drawing periods and spent the most time looking at the screen. We compared her with Ai, the other PRI female, to better understand their individual marking techniques and behaviours. By adapting to each one’s specific behaviour and previous experience with tool-assisted drawing on paper, we offered the females appropriate tools for making marks on the touchscreen. Our results indicate that electronic devices are not limiting in the expression of drawing behaviour. The females did not have the same drawing technique and also showed different types of engagement as motivation, which could not have been detected by only studying the completed drawings. By focusing more on the process rather than on the drawings themselves, we try to show inter-individual differences in drawing behaviour of chimpanzees and the relevance to adapt to it as experimenters.

The deep trabecular structure of first metacarpals in extant hominids.

Recent studies have associated subarticular trabecular bone distribution in the extant hominid first metacarpal (Mc1) with observed thumb use, to infer fossil hominin thumb use. Here, we analyze the entire Mc1 to test for interspecific differences in: (1) the absolute volume of trabecular volume fraction, (2) the distribution of the deeper trabecular network, and (3) the distribution of trabeculae in the medullary cavity, especially beneath the Mc1 disto-radial flange. Trabecular bone was imaged using micro-computed tomography in a sample of Homo sapiens (n= 11), Pan paniscus (n= 10), Pan troglodytes (n= 11), Gorilla gorilla (n= 10) and Pongo sp., (n= 7). Using Canonical Holistic Morphometric Analysis (cHMA), we tested for interspecific differences in the trabecular bone volume fraction (BV/TV) and its relative distribution (rBV/TV) throughout the Mc1, including within the head, medullary cavity, and base. P. paniscus had the highest, and H. sapiens the lowest, BV/TV relative to other species. rBV/TV distribution statistically distinguished the radial concentrations and lack of medullary trabecular bone in the H. sapiens Mc1 from all other hominids. H. sapiens and, to a lesser extent, G. gorilla also had a significantly higher trabecular volume beneath the disto-radial flange relative to other hominids. These results are consistent with differences in observed thumb use in these species and may also reflect systemic differences in bone volume fraction. The trabecular bone extension into the medullary cavity and concentrations beneath the disto-radial flange may represent crucial biomechanical signals that will aid in the inference of fossil hominin thumb use.

Vasopressin, and not oxytocin, receptor gene methylation is associated with individual differences in receptive joint attention in chimpanzees (Pan troglodytes).

Joint attention (JA) is an important milestone in human infant development and is predictive of the onset of language later in life. Clinically, it has been reported that children at risk for or with a diagnosis of autism spectrum disorder (ASD) perform more poorly on measures of JA compared to neurotypical controls. JA is not unique to humans but has also been reported in great apes and to a lesser extent in more distantly related monkeys. Further, individual differences in JA among chimpanzees are associated with polymorphisms in the vasopressin and oxytocin genes, AVPR1A and OXTR. Here, we tested whether individual variation in DNA methylation of OXTR and AVPR1A were associated with performance on JA tasks in chimpanzees. We found that individual differences in JA performance was associated with AVPR1A methylation, but not OXTR methylation in the chimpanzees. The collective results provide further evidence of the role of AVPR1A in JA abilities in chimpanzees. The results further suggest that methylation values for AVPR1A may be useful biomarkers for identifying individuals at risk for ASD or related neurodevelopmental disorders associated with impairments in JA abilities.

Surgical placement of implantable cardiac loop recorders in great apes.

Cardiovascular diseaseis the leading cause of morbidity and mortality in zoologically managed adult great apes, accounting for 29%-77% of adult deaths in the North American population depending on the species. In an effort to better understand the underlying causes of heart disease, implantable loop recorders (ILRs) have been used in some cases to monitor great apes with suspected or known cases of arrhythmia. This is a 10-year review of the Great Ape Heart Project's experience of implanting 21 ILRs in 7 gorillas (Gorilla gorilla gorilla; 9 total ILR devices), 5 chimpanzees (Pan troglodytes, 11 total ILR devices), and 1 orangutan (Pongo abelii, 1 ILR device) in an effort to develop effective methods for surgical implantation and remote collection of the data for analysis.

Long-Term Assessment of Captive Chimpanzees: Influence of Social Group Composition, Seasonality and Biographic Background.

Wild chimpanzees (Pan troglodytes) live in flexible fission-fusion societies with frequent changes in both group size and composition. These changes depend mostly on resource availability and individual social preferences yet in captivity are determined by housing organizations. During a period of seven years, we observed a group of sanctuary chimpanzees, focusing on how they adapted to changes in the group composition over time. Using linear mixed models (LMMs), factors such as group size, sex ratio, seasonality, and the individuals' sex and origin (wild caught vs. captive born) were considered in order to evaluate the impact on the chimpanzees' activity levels, the occurrence of undesired behaviors (abnormal and self-directed behaviors) and the social grooming networks. Our results indicate that the activity levels and the occurrence of undesired behaviors were impacted by changes in group composition and the individuals' biographic background. The colder season was marked by higher levels of activity and more time spent grooming. Moreover, it was the individuals' origin but not changes in group composition that affected social grooming, with wild-caught chimpanzees grooming far less frequently. Long-term observations are essential to evaluate, predict and detect potential benefits and/or issues of housing conditions while considering the social and physical environment.

Characterization of the superior olivary complex of chimpanzees (Pan troglodytes) in comparison to humans

The superior olivary complex (SOC) is a collection of nuclei in the hindbrain of mammals with numerous roles in hearing, including localization of sound sources in the environment, encoding temporal and spectral elements of sound, and descending modulation of the cochlea. While there have been several investigations of the SOC in primates, there are discrepancies in the descriptions of nuclear borders and even the presence of certain cell groups among studies and species. Herein, we aimed to clarify some of these issues by characterizing the SOC from chimpanzees using Nissl staining, quantitative morphometry and immunohistochemistry. We found the medial superior olive (MSO) to be the largest of the SOC nuclei and the arrangement of its neurons and peri-MSO to be very similar to humans. Additionally, we found neurons in the medial nucleus of the trapezoid body (MNTB) to be immunopositive for the calcium binding protein calbindin. Further, most neurons in the MNTB, and some neurons in the lateral nucleus of the trapezoid body were associated with large, calretinin-immunoreactive calyx terminals. Together, these findings indicate the organization of the SOC of chimpanzees is organized very similar to the SOC in humans and suggests modifications to this region among species consistent with differences in head/body size, restricted hearing range and sensitivity to low frequency sounds.

Modularity of the wrist in extant hominines.

Wrist shape varies greatly across primates and previous studies indicate that the numerous morphological differences among them are related to a complex mixture of phylogeny and function. However, little is known about whether the variation in these various anatomical differences is linked and to what extent the wrist bones vary independently. Here, we used 3D geometric morphometrics on a sample of extant hominines (Homo sapiens, Pan troglodytes, Gorilla gorilla, and Gorilla beringei), to find the model that best describes the covariation patterns among four of the eight carpals (i.e., capitate, lunate, scaphoid, and trapezium). For this purpose, 15 modular hypotheses were tested using the Covariance Ratio. Results indicate that there is a covariation structure common to all hominines, which corresponds to stronger covariation within each carpal as compared to the covariation between carpals. However, the results also indicate that that there is a degree of codependence in the variation of some carpals, which is unique in humans, chimpanzees, and gorillas, respectively. In humans there is evidence of associated shape changes between the lunate and capitate, and between the scaphoid and trapezium. This covariation between lunate and capitate is also apparent in gorillas, while chimpanzees display the greatest disassociation among carpals, showing low covariation values in all pairwise comparisons. Our analyses indicate that carpals have an important level of variational independence which might suggest a high degree of independent evolvability in the wrists of hominines, and that although weak, the structure of associated changes of these four carpals varies across genera. To our knowledge this is the first report on the patterns of modularity between these four wrist bones in the Homininae and future studies might attempt to investigate whether the anatomical shape associations among carpals are functionally related to locomotion and manipulation.

The association of astrogliosis and microglial activation with aging and Alzheimer's disease pathology in the chimpanzee brain.

Aging and neurodegenerative disorders, such as Alzheimer's disease (AD), trigger an immune response known as glial activation in the brain. Recent evidence indicates species differences in inflammatory responses to AD pathology, highlighting the need for additional comparative studies to further understand human-specific neuropathologies. In the present study, we report on the occurrence of astrogliosis, microglial activation, and their relationship with age and AD-like pathology in a cohort of male and female chimpanzees (Pan troglodytes). Chimpanzees with severe astrogliosis exhibited widespread upregulation of hypertrophic astrocytes immunoreactive for glial fibrillary acidic protein (GFAP) throughout all layers of the dorsolateral prefrontal cortex and a loss of the interlaminar palisade. In addition, extreme astrogliosis was associated with increased astrocyte density in the absence of significant microglial activation and AD lesions. A shift from decreased resting to increased phagocytotic microglia occurred with aging, although proliferation was absent and no changes in astrogliosis was observed. Vascular amyloid correlated with decreased astrocyte and microglia densities, while tau lesions were associated with morphological changes in microglia and greater total glia density and glia: neuron ratio. These results further our understanding of inflammatory processes within the chimpanzee brain and provide comparative data to improve our understanding of human aging and neuropathological processes.

Chimpanzees (Pan troglodytes) in U.S. Zoos, Sanctuaries, and Research Facilities: A Survey-Based Comparison of Species-Typical Behaviors.

A survey was sent to zoos, research facilities, and sanctuaries which housed chimpanzees. Data collected included information about 1122 chimpanzees’ age, sex, social group-size, rearing history, and enclosure. Respondents were also asked to indicate if certain behaviors had been observed in each chimpanzee over the prior two years. Species- typical behaviors (STBs) were queried, including copulation, tool-use, nest-building, and social grooming. Tool-use was reported present for 94.3% of the sample (n = 982), active social grooming for 85.7% (n = 1121), copulation for 68.3% (n = 863) and nest-building for 58.9% (n = 982). Of the subjects for whom we had data regarding all four STBs (n = 860), 45.6% were reported to engage in all four. Logistic regression analyses using forward Wald criteria were conducted to determine the best model for each STB based on the predictors of age, sex, rearing history, group-size, facility-type, and a sex-by-rearing interaction. The best model for copulation (χ2(6) = 124.62, p < 0.001) included rearing, group-size, facility-type, and the sex-by-rearing interaction. Chimpanzees were more likely to copulate if they were mother-reared, in larger groups, living in research facilities, and, if not mother-reared (NOTMR), more likely to copulate if they were female. The best model for tool-use retained the predictors of age category, facility-type, and sex-by-rearing (χ2(5) = 55.78, p < 0.001). Chimpanzees were more likely to use tools if they were adult, living in research facilities, and if NOTMR, were female. The best model for nest-building included facility-type and rearing (χ2(3) = 205.71, p < 0.001). Chimpanzees were more likely to build nests if they were MR and if they were living in zoos or in sanctuaries. The best model for active social grooming retained the predictors of age, sex, rearing, and type of facility (χ2(6) = 102.15, p < 0.001). Chimpanzees were more likely to engage in active social grooming if they were immature, female, mother-reared, and living in zoos. This research provides a basic behavioral profile for many chimpanzees living under human care in the United States and allows us to determine potential methods for improving the welfare of these and future chimpanzees in this population.