Retinoid X receptor beta polymorphisms do not explain functional differences in vitamins D and A response in Antineutrophil cytoplasmic antibody associated vasculitis patients

It has been suggested that the retinoid X receptor beta (RXRB) gene is a risk factor for Wegener's granulomatosis. We addressed if there is a functional difference in the response to retinoic acid (RA) and vitamin D in Antineutrophil cytoplasmic antibody (ANCA) associated systemic vasculitis (AASV) patients and if this was associated with RXRB genotypes. TNFα and IL-10 production were measured in whole blood assay from AASV patients (n = 51) and healthy controls (HC, n = 67). One micromolar of 1,25-(OH)₂ D3, 9-cis RA (9c-RA) or all-trans RA (ATRA) was added to the assay. Genotyping was performed for exons 7 and 2 of the RXRB gene and for a microsatellite in vicinity of the RXRB gene. Lipopolysaccharide (LPS) mediated TNFα production and IL-10 were significantly lower in patients. Addition of 1,25-(OH)₂ D3, ATRA or 9c-RA, blunted TNFα production, more pronounced in patients. Although all three compounds inhibited IL-10 production significantly in HC, only 1,25-(OH)₂ D3 was found to be effective in patients. Allele distribution of the RXRB microsatellite differed significantly between patients and HC. This was not found for the SNP in exons 2 and 7. Genotype of the latter correlated with the ability of 1,25-(OH)₂ D3 and ATRA to inhibit IL-10 production. We provide immunological evidence for a functional difference in vitamins D and A responsiveness in AASV patients. Since the inhibition of TNFα was more effective in patients, vitamin D supplementation might be an additional therapeutical approach.     

Infants use relative numerical group size to infer social dominance

Detecting dominance relationships, within and across species, provides a clear fitness advantage because this ability helps individuals assess their potential risk of injury before engaging in a competition. Previous research has demonstrated that 10- to 13-mo-old infants can represent the dominance relationship between two agents in terms of their physical size (larger agent = more dominant), whereas younger infants fail to do so. It is unclear whether infants younger than 10 mo fail to represent dominance relationships in general, or whether they lack sensitivity to physical size as a cue to dominance. Two studies explored whether infants, like many species across the animal kingdom, use numerical group size to assess dominance relationships and whether this capacity emerges before their sensitivity to physical size. A third study ruled out an alternative explanation for our findings. Across these studies, we report that infants 6–12 mo of age use numerical group size to infer dominance relationships. Specifically, preverbal infants expect an agent from a numerically larger group to win in a right-of-way competition against an agent from a numerically smaller group. In addition, this is, to our knowledge, the first study to demonstrate that infants 6–9 mo of age are capable of understanding social dominance relations. These results demonstrate that infants’ understanding of social dominance relations may be based on evolutionarily relevant cues and reveal infants’ early sensitivity to an important adaptive function of social groups.Competition for valuable resources such as mates, food, and territory (1) is commonplace across the animal kingdom. To minimize the cost of fighting (e.g., energy spent and personal injury or death), natural selection appears to have favored the emergence of cognitive adaptations that help individuals predict whether they stand a chance against an opponent (2–5). For example, many species, including ants, bees, birds, chimpanzees, and humans, appear to represent dominance relationships among conspecifics and use this information to decide whether to engage in or avoid a physical conflict (6–10). One such cue often associated with dominance ranking is physical size, with larger individuals often benefiting from greater strength and power over smaller individuals. Natural selection has also favored adaptations that exploit this inference, such that under threat, certain species adopt postures that make them appear bigger (11, 12) in order to intimidate an opponent.Underscoring the possibility that representations of social dominance may be part of humans’ evolved psychology, recent evidence has demonstrated that preverbal human infants infer social dominance relationships by comparing the physical size of two competing agents (13). In this earlier study, infants were introduced to two agents (one twice as large as the other), each with the goal of crossing to the opposite side of a platform. When both agents tried to cross the platform at the same time, their paths conflicted. Infants were shown two scenarios: one in which the larger agent yielded to the smaller agent, and one in which the smaller agent yielded to the larger agent. Although 10–13 mo olds expected a smaller agent to yield to a larger agent, younger infants (8–9 mo) failed to show any systematic belief about which agent should prevail. Therefore, only older infants were able to use the relative physical size of two competing agents to infer which one would get the right of way.Because younger infants did not reliably use physical size as a cue to social dominance, it remains unclear whether the younger infants were incapable of representing dominance relationships in general, or if they lacked sensitivity to this particular cue. To address this issue, the present study examined whether infants’ understanding of social dominance extends to cues beyond physical size—namely, to numerical group size, and if so, whether such a sensitivity emerges earlier in development.For many group-living animals, including social insects (7), wolves (14), hyenas (15), lions (16), primates (6), and human children and adults (5, 10), the ability to infer social dominance by assessing the numerical size of one’s own group relative to another is particularly important for survival (15, 17). The importance of this capacity to evaluate one’s own group size relative to another is illustrated by groups of chimpanzees patrolling their territory borders. To advertise the numerical strength of their group to others (18, 19) and deter opposing groups from approaching (20, 21), both males and females will engage noisy pant-hoot calling. In general, both chimpanzees and lions are more likely to approach if they outnumber intruders, but will stay silent and refrain from engaging in intergroup conflict if they do not (6, 16, 22, 23). Consequently, a group’s decision to engage in competition is more likely to occur if there are more individuals in one’s own group than in the opposing group (22, 24). Further, the relationship between numerical group size and inferences about social dominance has also been recently observed among children ages 6–8 y (5). School-aged children predicted that alliance strength would determine the likelihood of success in a conflict, such that two individuals aligned together were expected to win against a single individual. Coupled with the evidence reviewed from behavioral ecology, numerical group size may serve as an evolutionarily relevant cue to social dominance that humans are sensitive to within the first few years of life.Indeed, if young human infants have core knowledge of social relationships, as some have argued (13, 25), along with the capability to track the numerical size of small groups (26), it is possible that infants may be able to draw on both capacities to support inferences about the social dominance relationship between groups that differ in numerical size. If infants infer that individuals from larger groups are more dominant than individuals from smaller groups, this would demonstrate that infants’ understanding of social dominance can extend beyond the direct relationship between two competing individuals. Specifically, such a finding may shed light on whether infants already have an understanding of how social alliances operate—namely, that group members may help their own during a conflict, which confers a benefit to having more alliance members in close proximity during a conflict (10).Here, we explored whether infants can infer the dominance relationship between two agents from groups that differ in numerical size by modifying the methodology designed by Thomsen et al. (13). In our study, infants were first introduced to two groups that differed in numerical size (but equated for total surface area) and color. Next, infants were familiarized to an agent from each group independently achieving their goal of crossing a platform. When both of these agents attempted to cross the platform simultaneously, they bumped into one another. Therefore, the only way an agent could continue along their goal path was if one agent yielded to the other by moving out of the way.In study 1, we investigated whether 9- to 12-mo-old infants use numerical group size as a cue to social dominance. In study 2, we examined whether 6- to 9-mo-old infants (who have not yet been shown to represent social dominance relationships between individuals) would also be sensitive to the cue of numerical group size. Infants in studies 1 and 2 viewed the same sequence of events.