This paper seeks to bring together two previously separate research traditions: research on spatial orienting within the visual cueing paradigm and research into social cognition, addressing our tendency to attend in the direction that another person looks. Cueing methodologies from mainstream attention research were adapted to test the automaticity of orienting in the direction of seen gaze. Three studies manipulated the direction of gaze in a computerized face, which appeared centrally in a frontal view during a peripheral letter-discrimination task. Experiments 1 and 2 found faster discrimination of peripheral target letters on the side the computerized face gazed towards, even though the seen gaze did not predict target side, and despite participants being asked to ignore the face. This suggests reflexive covert and/or overt orienting in the direction of seen gaze, arising even when the observer has no motivation to orient in this way. Experiment 3 found faster letter discrimination on the side the computerized face gazed towards even when participants knew that target letters were four times as likely on the opposite side. This suggests that orienting can arise in the direction of seen gaze even when counter to intentions. The experiments illustrate that methods from mainstream attention research can be usefully applied to social cognition, and that studies of spatial attention may profit from considering its social function.

Abbreviations used in the paper: CCV, clathrin-coated vesicle; GEF, guanine nucleotide exchange factor; PP2A, protein phosphatase 2A; PtdIns(4,5)P 2 , phosphoinositide 4,5-bisphosphate; Tfn, transferrin; TfnR, tranferrin receptor.The online version of this article contains supplemental material.

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Aims/hypothesis Hypoxia may contribute to beta cell failure in type 2 diabetes and islet transplantation. The adaptive unfolded protein response (UPR) is required for endoplasmic reticulum (ER) homeostasis. Here we investigated whether or not hypoxia regulates the UPR in beta cells and the role the adaptive UPR plays during hypoxic stress. Methods Mouse islets and MIN6 cells were exposed to various oxygen (O 2 ) tensions. DNA-damage inducible transcript 3 (DDIT3), hypoxia-inducible transcription factor (HIF)1α and HSPA5 were knocked down using small interfering (si)RNA; Hspa5 was also overexpressed. db/db mice were used. Results Hypoxia-response genes were upregulated in vivo in the islets of diabetic, but not prediabetic, db/db mice. In isolated mouse islets and MIN6 cells, O 2 deprivation (1-5% vs 20%; 4-24 h) markedly reduced the expression of adaptive UPR genes, including Hspa5, Hsp90b1, Fkbp11 and spliced Xbp1. Coatomer protein complex genes (Copa, Cope, Copg [also known as Copg1], Copz1 and Copz2) and ER-to-Golgi protein trafficking were also reduced, whereas apoptotic genes (Ddit3, Atf3 and Trb3 [also known as Trib3]), c-Jun N-terminal kinase (JNK) phosphorylation and cell death were increased. Inhibition of JNK, but not HIF1α, restored adaptive UPR gene expression and ER-to-Golgi protein trafficking while protecting against apoptotic genes and cell death following hypoxia. DDIT3 knockdown delayed the loss of the adaptive UPR and partially protected against hypoxia-induced cell death. The latter response was prevented by HSPA5 knockdown. Finally, Hspa5 overexpression significantly protected against hypoxia-induced cell death. Conclusions/interpretation Hypoxia inhibits the adaptive UPR in beta cells via JNK and DDIT3 activation, but independently of HIF1α. Downregulation of the adaptive UPR contributes to reduced ER-to-Golgi protein trafficking and increased beta cell death during hypoxic stress.