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Although SHIP is a well-established suppressor of IgE plus Ag-induced degranulation and cytokine production in bone marrow-derived mast cells (BMMCs), little is known about its role in connective tissue (CTMCs) or mucosal (MMCs) mast cells. In this study, we compared SHIP’s role in the development as well as the IgE plus Ag and TLR-induced activation of CTMCs, MMCs, and BMMCs and found that SHIP delays the maturation of all three mast cell subsets and, surprisingly, that it is a positive regulator of IgE-induced BMMC survival. We also found that SHIP represses IgE plus Ag-induced degranulation of all three mast cell subsets and that TLR agonists do not trigger their degranulation, whether SHIP is present or not, nor do they enhance IgE plus Ag-induced degranulation. In terms of cytokine production, we found that in MMCs and BMMCs, which are poor producers of TLR-induced cytokines, SHIP is a potent negative regulator of IgE plus Ag-induced IL-6 and TNF-α production. Surprisingly, however, in splenic or peritoneal derived CTMCs, which are poor producers of IgE plus Ag-induced cytokines, SHIP is a potent positive regulator of TLR-induced cytokine production. Lastly, cell signaling and cytokine production studies with and without LY294002, wortmannin, and PI3Kα inhibitor-2, as well as with PI3K p85α−/− BMMCs and CTMCs, are consistent with SHIP positively regulating TLR-induced cytokine production via an adaptor-mediated pathway while negatively regulating IgE plus Ag-induced cytokine production by repressing the PI3K pathway.

During the past decade, progress has been made in addressing childhood obesity through policy and practice changes that encourage increased physical activity and access to healthy food. With the implementation of these strategies, an understanding of what works to prevent childhood obesity is beginning to emerge. The task now is to consider how best to spread, scale, and sustain promising childhood obesity prevention strategies. In this article we examine a project led by Nemours, a children's health system, to address childhood obesity. We describe Nemours's conceptual approach to spreading, scaling, and sustaining a childhood obesity prevention intervention. We review a component of a Nemours initiative in Delaware that focused on early care and education settings and its expansion to other states through the National Early Care and Education Learning Collaborative to prevent childhood obesity. We also discuss lessons learned. Focusing on the spreading, scaling, and sustaining of promising strategies has the potential to increase the reach and impact of efforts in obesity prevention and help ensure their impact on population health.

Streptomyces species include a group of aerobic actinomycetes that are generally considered to be saprophytes. Effusoconstrictive pericarditis of mixed etiology developed in a previously healthy patient. The cause of the chronic pericarditis was a Streptomyces species.