Flexible group cohesion and coordination, but robust leader–follower roles, in a wild social primate using urban space

Collective behaviour has a critical influence on group social structure and organization, individual fitness and social evolution, but we know little about whether and how it changes in anthropogenic environments. Here, we show multiple and varying effects of urban space-use upon group-level processes in a primate generalist—the chacma baboon (Papio ursinus)—within a managed wild population living at the urban edge in the City of Cape Town, South Africa. In natural space, we observe baboon-typical patterns of collective behaviour. By contrast, in urban space (where there are increased risks, but increased potential for high-quality food rewards), baboons show extreme flexibility in collective behaviour, with changes in spatial cohesion and association networks, travel speeds and group coordination. However, leader–follower roles remain robust across natural and urban space, with adult males having a disproportionate influence on the movement of group members. Their important role in the group's collective behaviour complements existing research and supports the management tactic employed by field rangers of curbing the movements of adult males, which indirectly deters the majority of the group from urban space. Our findings highlight both flexibility and robustness in collective behaviour when groups are presented with novel resources and heightened risks

Postpartum cessation of urban space use by a female baboon living at the edge of the City of Cape Town

Species with slow life history strategies that invest in few offspring with extended parental care need to adapt their behavior to cope with anthropogenic changes that occur within their lifetime. Here we show that a female chacma baboon (Papio ursinus) that commonly ranges within urban space in the City of Cape Town, South Africa, stops using urban space after giving birth. This change of space use occurs without any significant change in daily distance traveled or social interactions that would be expected with general risk-sensitive behavior after birth. Instead, we suggest this change occurs because of the specific and greater risks the baboons experience within the urban space compared to natural space, and because leaving the troop (to enter urban space) may increase infanticide risk. This case study can inform methods used to manage the baboons' urban space use in Cape Town and provides insight into how life history events alter individuals' use of anthropogenic environments

Dynamics of collective motion across time and species

Most studies of collective animal behaviour rely on short-term observations, and comparisons of collective behaviour across different species and contexts are rare. We therefore have a limited understanding of intra- and interspecific variation in collective behaviour over time, which is crucial if we are to understand the ecological and evolutionary processes that shape collective behaviour. Here, we study the collective motion of four species: shoals of stickleback fish (Gasterosteus aculeatus), flocks of homing pigeons (Columba livia), a herd of goats (Capra aegagrus hircus) and a troop of chacma baboons (Papio ursinus). First, we describe how local patterns (inter-neighbour distances and positions), and group patterns (group shape, speed and polarization) during collective motion differ across each system. Based on these, we place data from each species within a ‘swarm space’, affording comparisons and generating predictions about the collective motion across species and contexts. We encourage researchers to add their own data to update the ‘swarm space’ for future comparative work. Second, we investigate intraspecific variation in collective motion over time and provide guidance for researchers on when observations made over different time scales can result in confident inferences regarding species collective motion. This article is part of a discussion meeting issue ‘Collective behaviour through time’

Post-resolution macrophages shape long-term tissue immunity and integrity in a mouse model of pneumococcal pneumonia

Resolving inflammation is thought to return the affected tissue back to homoeostasis but recent evidence supports a non-linear model of resolution involving a phase of prolonged immune activity. Here we show that within days following resolution of Streptococcus pneumoniae-triggered lung inflammation, there is an influx of antigen specific lymphocytes with a memory and tissue-resident phenotype as well as macrophages bearing alveolar or interstitial phenotype. The transcriptome of these macrophages shows enrichment of genes associated with prostaglandin biosynthesis and genes that drive T cell chemotaxis and differentiation. Therapeutic depletion of post-resolution macrophages, inhibition of prostaglandin E2 (PGE2) synthesis or treatment with an EP4 antagonist, MF498, reduce numbers of lung CD4+/CD44+/CD62L+ and CD4+/CD44+/CD62L-/CD27+ T cells as well as their expression of the α-integrin, CD103. The T cells fail to reappear and reactivate upon secondary challenge for up to six weeks following primary infection. Concomitantly, EP4 antagonism through MF498 causes accumulation of lung macrophages and marked tissue fibrosis. Our study thus shows that PGE2 signalling, predominantly via EP4, plays an important role during the second wave of immune activity following resolution of inflammation. This secondary immune activation drives local tissue-resident T cell development while limiting tissue injur

Down-Regulation of miR-101 in Endothelial Cells Promotes Blood Vessel Formation through Reduced Repression of EZH2

Angiogenesis is a balanced process controlled by pro- and anti-angiogenic molecules of which the regulation is not fully understood. Besides classical gene regulation, miRNAs have emerged as post-transcriptional regulators of angiogenesis. Furthermore, epigenetic changes caused by histone-modifying enzymes were shown to modulate angiogenesis as well. However, a possible interplay between miRNAs and histone-modulating enzymes during angiogenesis has not been described. Here we show that VEGF-mediated down-regulation of miR-101 caused pro-angiogenic effects. We found that the pro-angiogenic effects are partly mediated through reduced repression by miR-101 of the histone-methyltransferase EZH2, a member of the Polycomb group family, thereby increasing methylation of histone H3 at lysine 27 and transcriptome alterations. In vitro, the sprouting and migratory properties of primary endothelial cell cultures were reduced by inhibiting EZH2 through up-regulation of miR-101, siRNA-mediated knockdown of EZH2, or treatment with 3-Deazaneplanocin-A (DZNep), a small molecule inhibitor of EZH2 methyltransferase activity. In addition, we found that systemic DZNep administration reduced the number of blood vessels in a subcutaneous glioblastoma mouse model, without showing adverse toxicities. Altogether, by identifying a pro-angiogenic VEGF/miR-101/EZH2 axis in endothelial cells we provide evidence for a functional link between growth factor-mediated signaling, post-transcriptional silencing, and histone-methylation in the angiogenesis process. Inhibition of EZH2 may prove therapeutic in diseases in which aberrant vascularization plays a role

Gene expression microarray analysis of early oxygen-induced retinopathy in the rat

Different inbred strains of rat differ in their susceptibility to oxygen-induced retinopathy (OIR), an animal model of human retinopathy of prematurity. We examined gene expression in Sprague–Dawley (susceptible) and Fischer 344 (resistant) neonatal rats after 3 days exposure to cyclic hyperoxia or room air, using Affymetrix rat Genearrays. False discovery rate analysis was used to identify differentially regulated genes. Such genes were then ranked by fold change and submitted to the online database, DAVID. The Sprague–Dawley list returned the term “response to hypoxia,” absent from the Fischer 344 output. Manual analysis indicated that many genes known to be upregulated by hypoxia-inducible factor-1α were downregulated by cyclic hyperoxia. Quantitative real-time RT-PCR analysis of Egln3, Bnip3, Slc16a3, and Hk2 confirmed the microarray results. We conclude that combined methodologies are required for adequate dissection of the pathophysiology of strain susceptibility to OIR in the rat

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. METHODS: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. FINDINGS: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50-0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38-0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45-0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. INTERPRETATION: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. FUNDING: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Anthropogenic noise alters dwarf mongoose responses to heterospecific alarm calls

Anthropogenic noise is an evolutionarily novel and widespread pollutant in both terrestrial and aquatic habitats. Despite increasing evidence that the additional noise generated by human activities can affect vocal communication, the majority of research has focused on the use of conspecific acoustic information, especially sexual signals. Many animals are known to eavesdrop on the alarm calls produced by other species, enhancing their likelihood of avoiding predation, but how this use of heterospecific information is affected by anthropogenic noise has received little empirical attention. Here, we use two field-based playback experiments on a habituated wild population of dwarf mongooses (Helogale parvula) to determine how anthropogenic noise influences the response of foragers to heterospecific alarm calls. We begin by demonstrating that dwarf mongooses respond appropriately to the alarm calls of sympatric chacma baboons (Papio ursinus) and tree squirrels (Paraxerus cepapi); fleeing only to the latter. We then show that mongoose foragers are less likely to exhibit this flee response to tree squirrel alarm calls during road-noise playback compared to ambient-sound playback. One explanation for the change in response is that noise-induced distraction or stress result in maladaptive behaviour. However, further analysis revealed that road-noise playback results in increased vigilance and that mongooses showing the greatest vigilance increase are those that do not subsequently exhibit a flee response to the alarm call. These individuals may therefore be acting appropriately: if the greater gathering of personal information indicates the absence of an actual predator despite an alarm call, the need to undertake costly fleeing behaviour can be avoided. Either way, our study indicates the potential for anthropogenic noise to interfere with the use of acoustic information from other species, and suggests the importance of considering how heterospecific networks are affected by this global pollutant

Intrinsic and extrinsic factors combine to affect baboon movements across natural and urban environments

Wildlife movement in urban environments can differ significantly from that in natural environments due to intrinsic factors (individual phenotype) as well as extrinsic factors (such as changes to the landscape and increased interactions with people). Here, we used tracking collars equipped with 1 Hz GPS to investigate the variation in fine-scale movement (individual step lengths, path tortuosity and residence times) of chacma baboons, Papio ursinus, across natural and urban environments in Cape Town, South Africa. We showed that the baboons exhibited limited interindividual differences in average movement (intrinsic factor: behavioural type), but large differences across environment (extrinsic factor: behavioural plasticity), where all baboons travelled faster and straighter, and spent less time in one location, when in urban space compared to natural space. We showed large intraindividual differences in baboon movement (behavioural predictability), indicating that some individuals exhibit greater consistency in movement than others. Finally, we showed an interaction between individual (ID) and environment (urban) for all metrics, where individuals differed in how much their movement in urban space changed compared to their movement in natural space. The individuals that changed their movement the most tended to be higher-ranking, socially connected baboons, which are the focus of the city’s baboon management programme, seeking to keep baboons out of urban areas. We therefore suspect these changes in movement between natural and urban space to be partly a result of human–baboon interactions. Taken together, our results show how individual animal movement can be impacted by changing environments, affecting certain baboon phenotypes more than others