On Being Stuck in Bengal: Immobility in the ‘age of migration’

Immobility raises awkward questions for theorists of migration. From their standpoint, migration is unusual behaviour that requires explanation. Its obverse—staying in place—is seen as an ‘obvious’ state of affairs that calls for no explanation. Yet assumptions about the ordinariness of immobility are insecure. For one thing, we know a great deal more about the mobile societies of early modern Asia; for another, Asian mobility in the era of high imperialism is much better understood. Yet despite these cumulative gains in our understanding of the scale of mobility in early-modern and modern Asia, and its acceleration in ‘the age of migration’, immobility continues to be seen as the ‘obvious’ state of affairs. This article suggests some preliminary answers to ‘the immobility paradox’, based on a study of the greater Bengal region. By analysing the impact of the intensifying links, in the late colonial era, between Bengal and the global economy, it shows that this varied widely for different people, in ways that had a profound bearing on their capacity to move. The article develops the notion of ‘deficits’ which worked to inhibit the mobility of particular groups and individuals. Physical frailty and obligations of care, it shows, were crucial factors in shaping immobility. Relations of gender and generation, and the inequalities embedded in these relations, produced ‘overabundances’—of obligations to people and places—that tied certain people down. Finally, it hints at the reasons why, and the ways in which, stayers-on have grown poorer.This article draws on research supported by the Arts and Humanities Research Council (AHRC) (UK)

Defective ATG16L1-mediated removal of IRE1α drives Crohn's disease-like ileitis.

ATG16L1$^{T300A}$, a major risk polymorphism in Crohn's disease (CD), causes impaired autophagy, but it has remained unclear how this predisposes to CD. In this study, we report that mice with Atg16l1 deletion in intestinal epithelial cells (IECs) spontaneously develop transmural ileitis phenocopying ileal CD in an age-dependent manner, driven by the endoplasmic reticulum (ER) stress sensor IRE1α. IRE1α accumulates in Paneth cells of Atg16l1$^{ΔIEC}$ mice, and humans homozygous for ATG16L1$^{T300A}$ exhibit a corresponding increase of IRE1α in intestinal epithelial crypts. In contrast to a protective role of the IRE1β isoform, hyperactivated IRE1α also drives a similar ileitis developing earlier in life in Atg16l1;Xbp1$^{ΔIEC}$ mice, in which ER stress is induced by deletion of the unfolded protein response transcription factor XBP1. The selective autophagy receptor optineurin interacts with IRE1α, and optineurin deficiency amplifies IRE1α levels during ER stress. Furthermore, although dysbiosis of the ileal microbiota is present in Atg16l1;Xbp1$^{ΔIEC}$ mice as predicted from impaired Paneth cell antimicrobial function, such structural alteration of the microbiota does not trigger ileitis but, rather, aggravates dextran sodium sulfate-induced colitis. Hence, we conclude that defective autophagy in IECs may predispose to CD ileitis via impaired clearance of IRE1α aggregates during ER stress at this site.This study was supported by the European Research Council under the European Community’s Seventh Framework Program (grant FP7/2007-2013)/ERC, agreement no. 260961 to A. Kaser and grant HORIZON2020/ERC, agreement no. 648889 to A. Kaser), the Wellcome Trust (Investigator Award 106260/Z/14/Z to A. Kaser and Principal Research Fellowship 2008/Z/16/Z to D. Ron), the Cambridge Biomedical Research Centre (A. Kaser), a Medical Research Council PhD for clinicians training fellowship (grant MR/N001893/1 to J. Bhattacharyya), fellowships from the European Crohn’s and Colitis Organization (M. Tschurtschenthaler and T.E. Adolph), the Research Training Group Genes, Environment, and Inflammation supported by the Deutsche Forschungsgemeinschaft (grant RTG 1743/1 to P. Rosenstiel), the SFB877 subproject B9 and CLVIII ExC 306 Inflammation at Interfaces (P. Rosenstiel), and the National Institutes of Health (grants DK044319, DK051362, DK053056, and DK088199 to the Harvard Digestive Diseases Center and grant DK0034854 to R.S. Blumberg)