Enforced Expression of Bcl-2 Selectively Perturbs Negative Selection of Dual Reactive Antibodies

We investigated the role of apoptosis in the development of B cell memory by analyzing the (p-azophenylarsonate) Ars response in a line of A strain mice in which expression of human Bcl-2 was enforced in the B cell compartment. Previous studies of the Ars immune response in these A. Bcl-2 mice, demonstrated that a large percentage of the antibodies expressed by the Ars induced memory B cell compartment had accumulated point mutations via somatic hypermutation that increased their affinity for both Ars and the autoantigen DNA (“dual reactive” antibodies). This was in sharp contrast to normal A strain mice which displayed no dual reactive B cells in their Ars induced memory B cell compartment. These data suggested that interference with apoptotic pathways regulated by Bcl-2 allows developing memory B cells that have acquired autoreactivity to bypass a peripheral tolerance checkpoint. Further studies of these mice, reported here, demonstrate that enforced expression of Bcl-2 does not alter serum antibody affinity maturation nor positive selection of B cells expressing somatically mutated antibody with an increased affinity for Ars. Moreover, the somatic hypermutation process was unaffected in A. Bcl-2 mice. Thus, enforced expression of Bcl-2 in A. Bcl-2 mice appears to selectively alter a negative selection process that operates during memory B cell differentiation

Ontogenetic changes in alarm-call production and usage in meerkats ( Suricata suricatta ): adaptations or constraints?

In many species, individuals suffer major mortality in their first year because of predation. Behaviours that facilitate successful escape are therefore under strong selection, but anti-predator skills often emerge gradually during an individual's early development. Using long-term data and acoustic recordings of alarm calls collected during natural predator encounters, we aimed to elucidate two largely unsolved issues in anti-predator ontogeny: (1) whether incorrect predator assignment is adaptively age-appropriate, given that vulnerability often changes during development, or whether age-related differences reflect true mistakes made by immature individuals; and (2) the extent to which the development of adult-like competence in alarm-call production and usage is simply a function of maturational processes or dependent upon experience. We found that young meerkats (Suricata suricatta) were less likely to give alarm calls than adults, but alarmed more in response to non-threatening species compared to adults. However, stimuli that pose a greater threat to young than adults did not elicit more calling from young; this argues against age-related changes in vulnerability as the sole explanation for developmental changes in calling. Young in small groups, who were more likely to watch out for predators, alarmed more than less vigilant young in larger groups. Moreover, despite similarities in acoustic structure between alarm call types, calls appeared in the repertoire at different rates, and those that were associated with frequently encountered predators were produced relatively early on. These results indicate that experience is a more plausible explanation for such developmental trajectories than maturatio

Decline and fall: The causes of group failure in cooperatively breeding meerkats.

Funder: MAVA FoundationFunder: Universität ZürichIn many social vertebrates, variation in group persistence exerts an important effect on individual fitness and population demography. However, few studies have been able to investigate the failure of groups or the causes of the variation in their longevity. We use data from a long-term study of cooperatively breeding meerkats, Suricata suricatta, to investigate the different causes of group failure and the factors that drive these processes. Many newly formed groups failed within a year of formation, and smaller groups were more likely to fail. Groups that bred successfully and increased their size could persist for several years, even decades. Long-lived groups principally failed in association with the development of clinical tuberculosis, Mycobacterium suricattae, a disease that can spread throughout the group and be fatal for group members. Clinical tuberculosis was more likely to occur in groups that had smaller group sizes and that had experienced immigration

Effects of cortisol administration on cooperative behavior in meerkat helpers

Experimental administration of stress hormones to meerkat helpers does not affect their contributions to cooperative activities. Previous work on cooperative breeders suggested that levels of stress hormones are related to helping behavior. We tested this experimentally by injecting meerkat helpers with cortisol, whilst matched controls received a saline injection. This did not lead to changes in cooperative behaviour, but induced females, and not males, to spend more time near pups and less time foragin

Flexible alarm calling in meerkats: the role of the social environment and predation urgency

Flexible vocal production has been demonstrated in several vertebrate species, with much work focusing on the role of the social "audience” in explaining variation in call production. It is, however, likely that the decision to call is an emergent property of both external and internal factors, and the extent to which these factors are integrated has been little investigated. We addressed this question by examining the production of alarm calls in wild male meerkats (Suricata suricatta) in different social environments and different predator-encounter contexts. Males searching for reproductive opportunities (rovers) were followed 1) in their home group and when prospecting either 2) solitarily or 3) in a coalition with other males. Results showed that conspecific presence influenced the production of flee-alarm and recruitment calls. Solitary rovers were less likely to produce flee-alarm calls compared with when they are with conspecifics, whether coalitionary rovers or the rover's home group. Experimentally elicited recruitment calls were also produced less when males were solitary than when in their home group. Bark vocalizations, emitted when meerkats were safe, were always produced irrespective of conspecific presence, indicating that these calls function to address predators. The probability of producing flee alarms also increased with the urgency of the predation event. Our results indicate that variation in alarm call production depends on whom the call is addressed to and also on the motivational state of the caller. We argue that neglecting to integrate internal and external factors when elucidating mechanisms underlying vocal production can potentially lead to misguided, parsimonious conclusions regarding vocal flexibility in animal

Resolving time conflicts in activity-based scheduling: A case study of Lausanne

In this paper, we present a novel activity-based scheduling model that combines a continuous optimisation framework for temporal scheduling decisions (i.e. activity timings and durations) with traditional discrete choice models for non-temporal choice dimensions (i.e. activity participation, number and type of tours, and considered destinations). The central concept of our approach is that individuals resolve time conflicts that arise from overlapping activities, e.g. needing to work and desiring to shop at the same time, in order to maximise their derived utility. Our proposed framework has three primary advantages over existing activity scheduling approaches: (i) the time-conflicts between different temporal scheduling decisions are considered and resolved jointly; (ii) individual behavioural preferences are incorporated in the scheduling problem using a utility-maximisation approach; and (iii) the framework is computationally scalable and can be used to estimate and simulate a city-scale case study in reasonable time. We introduce an estimation routine for the framework that allows model parameters to be calibrated using real-world historic data, as well as an efficient mixed-integer linear solver to optimally resolve temporal conflicts in simulated schedules. The estimation routine is applied and calibrated to a set of observed schedules in the Swiss mobility and transport microcensus. We then use the optimisation program with the estimated parameters to simulate activity schedules for a synthetic population for the city of Lausanne, Switzerland. We validate the model results against reported schedules in the microcensus data. The results demonstrate the capabilities of our approach to simulate realistic, flexible schedules for a real-world case-stud

Diurnal oscillations in gut bacterial load and composition eclipse seasonal and lifetime dynamics in wild meerkats.

Circadian rhythms in gut microbiota composition are crucial for metabolic function, yet the extent to which they govern microbial dynamics compared to seasonal and lifetime processes remains unknown. Here, we investigate gut bacterial dynamics in wild meerkats (Suricata suricatta) over a 20-year period to compare diurnal, seasonal, and lifetime processes in concert, applying ratios of absolute abundance. We found that diurnal oscillations in bacterial load and composition eclipsed seasonal and lifetime dynamics. Diurnal oscillations were characterised by a peak in Clostridium abundance at dawn, were associated with temperature-constrained foraging schedules, and did not decay with age. Some genera exhibited seasonal fluctuations, whilst others developed with age, although we found little support for microbial senescence in very old meerkats. Strong microbial circadian rhythms in this species may reflect the extreme daily temperature fluctuations typical of arid-zone climates. Our findings demonstrate that accounting for circadian rhythms is essential for future gut microbiome research

Signalling adjustments to direct and indirect environmental effects on signal perception in meerkats.

The efficiency of communication between animals is determined by the perception range of signals. With changes in the environment, signal transmission between a sender and a receiver can be influenced both directly, where the signal's propagation quality itself is affected, and indirectly where the senders or receivers' behaviour is impaired, impacting for example the distance between them. Here we investigated how meerkats (Suricata suricatta) in the Kalahari Desert adjust to these challenges in the context of maintaining group cohesion through contact calls. We found that meerkats changed their calling rate when signal transmission was affected indirectly due to increased dispersion of group members as during a drought, but not under typical wet conditions, when signal transmission was directly affected due to higher vegetation density. Instead under these wetter conditions, meerkats remained within proximity to each other. Overall, both direct and indirect environmental effects on signal perception resulted in an increased probability of groups splitting. In conclusion, we provide evidence that social animals can flexibly adjust their vocal coordination behaviour to cope with direct and indirect effects of the environment on signal perception, but these adjustments have limitations