Rensch’s and Bergmann’s Rules in Cis-Andean South-American Howler Monkeys (Mammalia: Alouatta)

Howler monkeys (genus Alouatta) are large folivorous primates living in South America. We tested for the application of both Rensch’s rule and Bergmann’s rule to body size variation in Alouatta. We found that Rensch’s rule does apply in howlers. In Alouatta, males exploit dominance rank competition, and take advantage from seasonal abundance of high nutritious fruit supply in their diet. This mating system and dietary charateristics suggest positive male selection for body size is responsible for Rensch’s rule. However, since folivory favors large body size in primates (to lower mass specific metabolic rate) and it is the primary dietary habitus in howlers, larger species do occur in the Amazon basin, originating a reversed Bergmann’s rule pattern for both males and females at the interspecific level. The spatial and phylogenetic components of such body size patterns of variation are both important, implying Alouatta ecomorphological differences to occur above the species level, justifying their non-overlapping geographic distribution

Club cell CREB regulates the goblet cell transcriptional network and pro-mucin effects of IL-1B

Introduction: Club cells are precursors for mucus-producing goblet cells. Interleukin 1β (IL-1B) is an inflammatory mediator with pro-mucin activities that increases the number of mucus-producing goblet cells. IL-1B-mediated mucin production in alveolar adenocarcinoma cells requires activation of the cAMP response element-binding protein (CREB). Whether the pro-mucin activities of IL-1B require club cell CREB is unknown.Methods: We challenged male mice with conditional loss of club cell Creb1 and wild type littermates with intra-airway IL-1B or vehicle. Secondarily, we studied human “club cell-like” H322 cells.Results: IL-1B increased whole lung mRNA of secreted (Mucin 5ac, Mucin 5b) and tethered (Mucin 1, Mucin 4) mucins independent of genotype. However, loss of club cell Creb1 increased whole lung mRNA of member RAS oncogene family (Rab3D), decreased mRNA of the muscarinic receptor 3 (M3R) and prevented IL-1B mediated increases in purinergic receptor P2Y, (P2ry2) mRNA. IL-1B increased the density of goblet cells containing neutral mucins in wildtype mice but not in mice with loss of club cell Creb1. These findings suggested that club cell Creb1 regulated mucin secretion. Loss of club cell Creb1 also prevented IL-1B-mediated impairments in airway mechanics. Four days of pharmacologic CREB inhibition in H322 cells increased mRNA abundance of forkhead box A2 (FOXA2), a repressor of goblet cell expansion, and decreased mRNA expression of SAM pointed domain containing ETS transcription factor (SPDEF), a driver of goblet cell expansion. Chromatin immunoprecipitation demonstrated that CREB directly bound to the promoter region of FOXA2, but not to the promoter region of SPDEF. Treatment of H322 cells with IL-1B increased cAMP levels, providing a direct link between IL-1B and CREB signaling.Conclusion: Our findings suggest that club cell Creb1 regulates the pro-mucin properties of IL-1B through pathways likely involving FOXA2