Cen Chen

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.

This study examined risk and protection for adolescent problem behavior and depressive symptomatology in an average-risk sample of 11th graders. Using a socioecological perspective, we aggregated risk factors for adolescent problem behavior and depressed mood by 3 social contexts: i.e., family and peer contexts, and a context comprising the most important nonparental adult in respondents' lives. Protective factors associated with these 3 contexts were also included in the analyses. We tested separate models for predicting problem behaviors and depressive symptoms; the models demonstrated divergent validity. Risk and protective factors accounted for 49% of the variance in problem behavior and 49% in depressive symptoms. Tests of interactions between risk-aggregates and protective factors yielded several significant cross-context buffering effects in the problem behavior model, but none in the depressive symptoms model. Parents' and VIP's perceived sanctions buffered adolescents against high risk for problem behavior emanating from the peer context. Additionally, perceived peers' sanctions buffered youths against risk emanating from each of the 3 contexts.

Objectives: The aim of the current study was to differentiate between neural activity that represents neural anomalies that are responsible for persistent developmental stuttering from the activity that is a result of compensating for stuttering. This was done by investigating alterations to the intrinsic functional architecture of speech-language processes of patients with PDS before and after a short-term intervention. Methods: The resting-state functional connectivity and cortical thickness were examined before and after the intervention. The structural data were used to validate the functional results. Fifteen stuttering patients who received intervention, 13 stuttering patients who did not receive intervention, and 13 fluent controls participated. Results: Before the intervention, both groups of PDS patients showed significant RSFC and cortical thickness reductions in the left pars-opercularis and RSFC increases in the cerebellum, as compared to fluent controls. The intervention was effective in reducing stuttering in PDS- patients and lowering their RSFC in the cerebellum to the level of fluent controls. The intervention effect was specific to the PDS-group. The intervention did not change RSFC and cortical thickness in the left PO, which remained at its preintervention level. Conclusions: The results suggest that the left PO is a locus where the intrinsic functional architecture of speech-language processes is altered in PDS patients, suggesting an etiologic role of this region in PDS. The cerebellum showed intervention-induced neural reorganization, suggesting a compensatory response when stuttering occurs. Copyright © 2012 by AAN Enterprises, Inc.

As part of a larger program of research on the nature of adolescents' relationships with very important nonparental adulis, a community sample of 243 eleventh graders was surveyed, and a subgroup of 55 adolescents and their VIPs were interviewed about the nature and quality of their relationships. Results showed that adolescent-VIP relationships were a normative component of adolescent development, not a result of problems in adolescents' lives; adolescent-VIP relationships were generally of high quality ; there were significant differences between kin and nonkin VIPs in terms of the duration of relationships and frequency of contact, but not in the quality of relationships; and VIPs whom, adolescents designated as extremely important were distinguished from other VIPs in terms of providing a higher level of social support and a higher frequency of contact. Theoretical and practical implications of these findings are discussed.