A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations

Perturbations in cellular chloride concentrations can affect cellular pH, autophagy and lead to the onset of apoptosis. With this in mind synthetic ion transporters have been used to disturb cellular ion homeostasis and thereby induce cell death; however, it is not clear whether synthetic ion transporters can also be used to disrupt autophagy. Here we show that squaramide-based ion transporters enhance the transport of chloride anions in liposomal models and promote sodium chloride influx into the cytosol. Liposomal and cellular transport activity of the squaramides is shown to correlate with cell death activity, which is attributed to caspase-dependent apoptosis. One ion transporter was also shown to cause additional changes in the lysosomal pH which leads to impairment of lysosomal enzyme activity and disruption of autophagic processes. This disruption is independent of the initiation of apoptosis by the ion transporter. This study provides the first experimental evidence that synthetic ion transporters can disrupt both autophagy and induce apoptosis

Interfunctional Conflict, Conflict Resolution Styles, and New Product Success: A Four-Culture Comparison

This paper develops a model relating innovation success to the level of interfunctional conflict and conflict resolution methods. The model suggests a concave relationship between performance and the level of interfunctional conflict among marketing, R&D, and manufacturing. It also conjectures that both national culture and the level of interfunctional conflict influence the effectiveness of different conflict resolution methods. An empirical test of the proposed framework involves a survey of 968 marketing managers from Japan, Hong Kong, the United States, and Great Britain. The results provide general support for the model's predictions and reveal several significant cross-national differences.New Product Development, Conflict Management, Cross-function Integration, Cross-cultural Study