Despite the mechanisms for endogenous nitroxyl (HNO) production and action being incompletely understood, pharmacological donors show broad therapeutic promise and are in clinical trials. Mass spectrometry and site-directed mutagenesis showed that chemically distinct HNO donors 1-nitrosocyclohexyl acetate or Angeli’s salt induced disulfides within cGMP-dependent protein kinase I-alpha (PKGIα), an interdisulfide between Cys42 of the two identical subunits of the kinase and a previously unobserved intradisulfide between Cys117 and Cys195 in the high affinity cGMP-binding site. Kinase activity was monitored in cells transfected with wildtype (WT), Cys42Ser or Cys117/195Ser PKGIα that cannot form the inter- or intradisulfide, respectively. HNO enhanced WT kinase activity, an effect significantly attenuated in inter- or intradisulfide-deficient PKGIα. To investigate whether the intradisulfide modulates cGMP binding, real-time imaging was performed in vascular smooth muscle cells expressing a FRET-biosensor comprising the cGMP-binding sites of PKGIα. HNO induced FRET changes similar to those elicited by an increase of cGMP, suggesting that intradisulfide formation is associated with activation of PKGIα. Intradisulfide formation in PKGIα correlated with enhanced HNO-mediated vasorelaxation in mesenteric arteries in vitro and arteriolar dilation in vivo in mice. HNO induces intradisulfide formation in PKGIα, inducing the same effect as cGMP binding, namely kinase activation and thus vasorelaxation.
Purpose This study aims to investigate marketing capabilities that represent the marketing mix from an adaptive perspective: brand management, customer relationship management, price management and multi-channel management. Also, this study identifies how adaptive marketing capabilities (AMCs) enrich superior innovativeness and speed-to-market regarding innovation orientation and marketing orientation as the two critical functions. Design/methodology/approach A questionnaire-based research was performed to test the proposed hypotheses. The data were collected from predominately marketing or research and development managers/senior specialists in 247 firms. Findings Strategic orientations that cover market and innovation orientation facilitate a firm’s AMCs, positively affecting its innovativeness and speed-to-market. Also, AMCs mediate the relationship between strategic orientations, and innovativeness, and speed-to-market. Further, this study confirms the complementary association of AMC-related variables in enhancing firm innovativeness and speed-to-market. Research limitations/implications This study is subject to the limitations inherent in survey design, particularly convenient sampling and single informants. Originality/value This study broadens understanding of dynamic capabilities theory by examining how marketing capabilities can be enhanced and examined from an adaptive perspective for firms. This study also presents a model for the potential relationships among strategic orientations, AMCs, innovativeness and speed-to-market.
New product development (NPD) projects are costly, and fragile against failures as compared to other structures. This study has a holistic view of team factors to examine their relationship with team communication. Communication contributes to technical and practical processes such as learning, new idea development, and creativity. Trust has become prominent by affecting outcomes and processes indirectly, and changing relationships within team. This paper attempted to offer a contribution to the technology and innovation management (TIM) literature by presenting a model for researchers and project managers to understand potential interrelationships among team level factors (team autonomy, stability, member experience, and empowerment), team trust, and team formal and informal communication in NPD teams.
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