Anti-FICD monoclonal antibody, clone 3B23

The endoplasmic reticulum (ER)-localized Hsp70 chaperone BiP affects protein folding homeostasis and the response to ER stress. Reversible inactivating covalent modification of BiP is believed to contribute to the balance between chaperones and unfolded ER proteins, but the nature of this modification has so far been hinted at indirectly. We report that deletion of FICD, a gene encoding an ER-localized AMPylating enzyme, abolished detectable modification of endogenous BiP enhancing ER buffering of unfolded protein stress in mammalian cells, whilst deregulated FICD activity had the opposite effect. In vitro, FICD AMPylated BiP to completion on a single residue, Thr518. AMPylation increased, in a strictly FICD-dependent manner, as the flux of proteins entering the ER was attenuated in vivo. In vitro, Thr518 AMPylation enhanced peptide dissociation from BiP 6-fold and abolished stimulation of ATP hydrolysis by J-domain cofactor. These findings expose the molecular basis for covalent inactivation of BiP.

This study uses cognitive categorization theory to explain why exposure to foreign cultures and environments results in difficulties for exporting firms. The phenomenon is labeled "foreignness-induced cognitive disorientation" (FICD). The study investigates how FICD affects the establishment and maintenance of cross-border business relationships. An instrument to measure FICD is developed using survey data from exporters. Then, FICD's negative impact on interfirm trust and export performance is assessed with structural equations modeling. Furthermore, a moderation test shows that when FICD is high, the influence of trust on the performance of exporting firms becomes negative. In addition, the analysis of a longitudinal data set with logistic regression verifies how FICD is negatively associated with the survival of export relationships. Finally, using a small but rare dyadic data set, the research shows how the FICD of one exchange party has an indirect negative influence on its overseas partner's trust. Drawing on cognitive categorization theory, this research shows how the basic processes of the human brain are the roots of most intercultural issues. The study provides a fundamental explanation of how FICD is a major disturbance to the initiation and maintenance of cross-border business relationships. It questions current methods to mitigate foreignness in international business and opens the way to new investigations that should facilitate cross-cultural interactions for international firms and their staff.