Primates and disability: Behavioral flexibility and implications for resilience to environmental change.

Congenital malformations, conditions, injuries, and illness can lead to long-term physical impairment and disability in nonhuman primates. How individual primates change their behaviors flexibly to compensate for their disabilities can inform our understanding of their resilience and ability to adjust to environmental change. Here, we synthesize the literature on nonhuman primates and disability, addressing the questions: how does disability influence behavior in primates? What insights can we take from the literature to better understand and predict the capacity of primates to modify their behaviors in the face of human-induced environmental change? We conducted a systematic review of the literature on spontaneous physical impairment and disability in captive, free-ranging, and wild primates. We surveyed 2807 articles on Web of Science and Scopus and identified 114 studies that fit our predetermined inclusion criteria. Behavioral plasticity, maternal and conspecific care, and the potential for innovation of novel behaviors allow many primates with disabilities to compensate when faced with challenges that are outside the scope of usual circumstances. We also found that 60% of the publications connected primate physical impairment and disability to human activities, suggesting an entangled relationship among humans, the environment, and primate disability. Disability and physical impairments provide an opportunity to examine how primates modify their behavior when presented with challenging conditions, and their potential resilience to a changing environment.

Mothers of disabled infants had higher cortisol levels in a free-ranging group of Japanese macaques (Macaca fuscata).

Glucocorticoids (GCs) are hormones released in response to stressors and can provide insight into an organism's physiological well-being. Experiencing chronic challenges to homeostasis is associated with significant deviations from baseline fecal GCs (fGCs) in many species, providing a noninvasive biomarker for assessing stress. In the group of free-ranging Japanese macaques (Macaca fuscata) at the Awajishima Monkey Center in Japan, ~17% have congenital limb malformations. We collected 646 fecal samples from 27 females over three consecutive birth seasons (May-August) and analyzed them using enzyme immunoassay to extract fGCs. We explored the relationship between fGC levels and individual (physical impairment and reproductive status), social (dominance rank and availability of kin for social support), and ecological variables (exposure to potential predators, rainfall, and wild fruit availability). A disabled infant was associated significantly with higher fGC in the mother; however, physical impairment in adult females was not significantly related to fGC levels. Females with higher dominance rank had significantly lower fGC levels than lower ranking females. Other factors did not relate significantly to fGC. These results suggest that providing care that meets the support needs of disabled infants poses a physiological challenge for mothers and suggests that physically impaired adults are able to effectively compensate for their disabilities with behavioral plasticity. Once an individual with congenital limb malformations survives infancy through their mother's care, physical impairment does not appear to influence fGC values, while social variables like dominance rank significantly influenced cortisol values in free-ranging female Japanese macaques.

No food left behind: foraging route choices among free-ranging Japanese macaques (Macaca fuscata) in a multi-destination array at the Awajishima Monkey Center, Japan.

Animals must make route choices every day when moving through their habitat while foraging. Choosing an optimal route can be cognitively costly, and primates and other animals have been shown to use simple heuristics, "rules of thumb", to make foraging route choices. We investigated the potential use of heuristics among foraging free-ranging Japanese monkeys (Macaca fuscata) during solitary foraging trials. We also investigated the potential influence of individual variables (age and sex) and social variables (presence in the central group, presence of potential inter- and intraspecific competitors), on the use of heuristics, route length and trial time. We used a multi-destination foraging experiment with 6 platforms in a (4 m × 8 m) Z-array, completed by 29 Japanese macaques in 155 runs at the Awajishima Monkey Center in Japan. Our results showed that the macaques chose routes consistent with heuristics (e.g. nearest neighbour heuristic 19.4%, convex hull heuristic 4.5%) and selected optimal routes (shortest path in 23.9% of the trials). We also identified a potential new heuristic that was used most frequently, that we termed the "sweep heuristic" (27.1% of trials), which we interpreted as a strategy to deal with competitive foraging trade-offs - choosing routes to prioritize not leaving isolated food pieces behind. Age was significantly related to trial time; juvenile macaques were faster than adults and young adults, using speed to gain access to resources. Solitary trials with conspecifics present took significantly longer routes. Our results suggest that contextual factors led to variation in Japanese macaque decision-making, and we suggest that the preferential use of a sweep heuristic may have been a response to high intragroup competition.

Microvascular significance of TGF-ß axis activation in COVID-19.

As 2023 approaches, the COVID-19 pandemic has killed millions. While vaccines have been a crucial intervention, only a few effective medications exist for prevention and treatment of COVID-19 in breakthrough cases or in unvaccinated or immunocompromised patients. SARS-CoV-2 displays early and unusual features of micro-thrombosis and immune dysregulation that target endothelial beds of the lungs, skin, and other organs. Notably, anticoagulation improves outcomes in some COVID-19 patients. The protein transforming growth factor-beta (TGF-ß1) has constitutive roles in maintaining a healthy microvasculature through its roles in regulating inflammation, clotting, and wound healing. However, after infection (including viral infection) TGF-ß1 activation may augment coagulation, cause immune dysregulation, and direct a path toward tissue fibrosis. Dysregulation of TGF-ß signaling in immune cells and its localization in areas of microvascular injury are now well-described in COVID-19, and such events may contribute to the acute respiratory distress syndrome and skin micro-thrombosis outcomes frequently seen in severe COVID-19. The high concentration of TGF-ß in platelets and in other cells within microvascular thrombi, its ability to activate the clotting cascade and dysregulate immune pathways, and its pro-fibrotic properties all contribute to a unique milieu in the COVID-19 microvasculature. This unique environment allows for propagation of microvascular clotting and immune dysregulation. In this review we summarize the physiological functions of TGF-ß and detail the evidence for its effects on the microvasculature in COVID-19. In addition, we explore the potential role of existing TGF-ß inhibitors for the prevention and treatment of COVID-19 associated microvascular thrombosis and immune dysregulation.

Mild movement sequence repetition in five primate species and evidence for a taxonomic divide in cognitive mechanisms.

When animals forage, they face complex multi-destination routing problems. Traplining behaviour-the repeated use of the same route-can be used to study how spatial memory might evolve to cope with complex routing problems in ecologically distinct taxa. We analyzed experimental data from multi-destination foraging arrays for five species, two cercopithecine monkeys (vervets, Chlorocebus pygerythrus, and Japanese macaques, Macaca fuscata) and three strepsirrhines (fat-tailed dwarf lemurs, Cheirogaleus medius, grey mouse lemurs, Microcebus murinus, and aye-ayes, Daubentonia madagascariensis). These species all developed relatively efficient route formations within the arrays but appeared to rely on variable cognitive mechanisms. We found a strong reliance on heuristics in cercopithecoid species, with initial routes that began near optimal and did not improve with experience. In strepsirrhines, we found greater support for reinforcement learning of location-based decisions, such that routes improved with experience. Further, we found evidence of repeated sequences of site visitation in all species, supporting previous suggestions that primates form traplines. However, the recursive use of routes was weak, differing from the strategies seen in well-known traplining animals. Differences between strepsirrhine and cercopithecine strategies may be the result of either ecological or phylogenetic trends, and we discuss future possibilities for disentangling the two.

Proximity and grooming patterns reveal opposite-sex bonding in Rwenzori Angolan colobus monkeys (Colobus angolensis ruwenzorii).

Close proximity and social grooming are important bonding mechanisms in primates. These behaviors show the social structure of a species and many studies have found positive correlations between the degree of kinship and grooming and proximity. We used 1 year of data collected via instantaneous scan sampling on a large "supertroop" of Colobus angolensis ruwenzorii at Lake Nabugabo, Uganda, to examine partner preferences for grooming and nearest neighbors in each age-sex class. Little is known about this species, so we based our hypotheses on congeners. Of the five species of black-and-white colobus, data on sex-biased dispersal patterns are available for three (C. guereza, C. vellerosus, and C. polykomos), all of which show male-biased dispersal with occasional female dispersal. We thus predicted that female C. a. ruwenzorii would be more strongly bonded than males, showing greater proximity and grooming. We did not expect bonding between the sexes since congeners do not show this pattern. We found that among adult dyads, males and females were more likely to be found in loose proximity, and to groom, than would be expected given group composition. Conversely, both males and females had relatively weak same-sex relationships. Between the sexes, adult males had higher proximity and grooming indices with adult females without infants than with females with infants. These observations indicate that this subspecies is cross-bonded and that both sexes may disperse. Furthermore, our findings suggest that the social organization and social structure of C. a. ruwenzorii differ greatly from other black-and-white colobus species.

Changes in levels of D1, D2, or NMDA receptors during withdrawal from brief or extended daily access to IV cocaine.

We previously reported that brief (1 h), but not extended (6 h), daily access to cocaine results in a sensitized locomotor response to cocaine and in elevated c-Fos immunoreactivity and DAT binding in the nucleus accumbens (N.Acc) core. In order to better our understanding of the neural adaptations mediating the transition from controlled drug use to addiction, the current experiments were set to further explore the neural adaptations resulting from these two access conditions. Rats received either brief daily access to saline or cocaine, or brief daily access followed by extended daily access to cocaine. Subjects were then sacrificed either 20 min, or 14 or 60 days, after the last self-administration session. Samples of the ventral tegmental area (VTA), N.Acc core and shell, dorsal striatum, and medial prefrontal cortex (mPFC) were taken for analysis of D1 ([3H]SCH-23390), D2 ([3H]Spiperone), and NMDA ([3H]MK-801) receptor binding (using the method of receptor autoradiography). At 20 min into withdrawal, D2 receptors were elevated and NMDA receptors were reduced in the mPFC of the brief access animals while D1 receptors were elevated in the N.Acc shell of the extended access animals, compared to saline controls. D2 receptors were reduced in the N.Acc shell of the brief access animals compared to saline controls after 14 days, and compared to extended access animals after 60 days of withdrawal. In summary, extended access to cocaine resulted in only transient changes in D1 receptors binding. These results suggest that the development of compulsive drug use is largely unrelated to changes in total binding of D2 or NMDA receptors.

A rare case of gallbladder fistulation with a 60-year-old appendicectomy scar.

We present an extremely unusual case of an external biliary fistula in an 87-year-old woman who presented with a 1-day history of spontaneous green discharge from a 60-year-old appendicectomy scar. Examination revealed a sinus in the right iliac fossa overlying her appendicectomy scar, with a raised white cell count and C reactive protein. A CT scan revealed a complex fistula connecting the gallbladder to the subcutaneous tissue in the right flank, which further connected inferiorly with a fistula to the previous appendicectomy scar and a small iliopsoas collection. Endoscopic retrograde cholangiopancreatography revealed several stones in the common bile duct, which were removed using a balloon catheter. The patient was further managed with a long course of antibiotics and discharged with a long-term drainage bag. A literature search revealed no previously reported cases of an external biliary fistula communicating with an appendicectomy scar.