Background Interleukin-4 (IL-4) and STAT6 play an important role in progression of allergic airway disease (AAD) or asthma. IL-4 and STAT6 mediate T helper 2 (Th2) responses in T cells, and immunoglobulin class switching to IgE in B cells. Both, Th2 responses and IgE promote the asthmatic condition. We have previously demonstrated that PARP-14, a member of the poly ADP-ribose polymerase (PARP) family of proteins regulates the transcription function of STAT6. However, the role of PARP-14 in AAD is not known. Objective Here we investigate the role of PARP-14 and the enzyme activity associated with it in AAD dependent on airway hyper-responsiveness (AHR) and lung inflammation. We also elucidate the mechanism by which PARP-14 regulates AAD. Methods The role of PARP-14 and its enzyme activity in AAD and Th2 differentiation were examined using a mouse model of AAD and in vitro T helper cell differentiation. Results PARP-14 deficient animals when compared to controls show reduced lung pathology and IgE. Treating mice with a pharmacological inhibitor for PARP activity reduced the severity of AHR and lung inflammation. Mechanistically, our data indicate that PARP-14 and its enzyme activity aid in the differentiation of T cells towards a Th2 phenotype by regulating the binding of STAT6 to the Gata3 promoter. Conclusion PARP-14 and the catalytic activity associated with it promote Th2 differentiation and AAD in a murine model, and targeting PARP-14 may be a potential new therapy for allergic asthma.

Almost all bile leaks and many bile duct injuries can be managed successfully by endoscopists. Selected proximal injuries can be treated by interventional radiologists with modest success. Outcomes of bile duct injuries are best with surgical management and in patients who are stented for more than 6 months.

Verwechslung ausgeschlossen: Ein Wasserstoffbrückenmotiv, das auf hexafluorierten Alkoholfunktionen beruht (siehe Bild; rot O, gelb F), aktiviert elektrophile Substrate. Die katalytische Aktivität des Systems wurde an der Ringöffnungspolymerisation einer Vielzahl gespannter Heterocyclen demonstriert. Polymere mit vorhersagbarem Molekulargewicht, niedriger Polydispersität und verlässlichen Endgruppen wurden erhalten.magnified image

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Cooperative interaction between multiple chiral centers dictates the absolute handedness of structural folding. We have designed and prepared a series of chiral C 3 -symmetric tris(Nsalicylidenamine) derivatives that adopt three-blade propeller-like conformations. Synthetic access to an expanded family of such constructs was aided by enzymatic resolution and C-C cross-coupling reactions of aryl-substituted chiral propargylic alcohol derivatives. These key structural components were integrated into molecular propellers of predetermined helical screw sense. Through comparative studies on a homologous set of molecules, we found that installation of phenylene-ethynylene-derived π-conjugation profoundly affected the stabilities of the helically folded structures, as evi-