Connal Lee

Exaggerated contraction of airway smooth muscle is the major cause of symptoms in asthma, but the mechanisms that prevent exaggerated contraction are incompletely understood. Here, we showed that integrin α 9β 1on airway smooth muscle localizes the polyamine catabolizing enzyme spermidine/spermine N 1-acetyltransferase in close proximity to the lipid kinase PIP5K1γ. As PIP5K1γ is the major source of PIP2 in airway smooth muscle and its activity is regulated by higher-order polyamines, this interaction inhibited IP3-dependent airway smooth muscle contraction. Mice lacking integrin α 9β 1 in smooth muscle had increased airway responsiveness in vivo, and loss or inhibition of integrin α 9β 1 increased in vitro airway narrowing and airway smooth muscle contraction in murine and human airways. Contraction was enhanced in control airways by the higher-order polyamine spermine or by cell-permeable PIP2, but these interventions had no effect on airways lacking integrin α 9β 1 or treated with integrin α 9β 1-blocking antibodies. Enhancement of SSAT activity or knockdown of PIP5K1γ inhibited airway contraction, but only in the presence of functional integrin α 9β 1. Therefore, integrin α 9β 1 appears to serve as a brake on airway smooth muscle contraction by recruiting SSAT, which facilitates local catabolism of polyamines and thereby inhibits PIP5K1γ. Targeting key components of this pathway could thus lead to new treatment strategies for asthma.

Adverse adulthood outcomes are well documented among youth who age out of foster care. However, not all youth who age out of care experience deleterious adult outcomes, despite struggling with similar challenges during the transition from adolescence to adulthood. Childhood maltreatment, which places youth at greater risk for later maladaptive functioning and psychopathology, may partially explain poor adjustment outcomes in adulthood. Similarly, a history of unstable placements and residing in institutional congregate care settings may also contribute to hardship during this time. However, none of these factors help to explain how some young people aging out of care manage to achieve stability while transitioning into adulthood. This article reviews the literature through the lens of the identity capital framework, and discusses the applicability of this framework to the experiences of youth aging out of foster care. © 2014 Elsevier Ltd.