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As a highly regenerative organ, the intestine is a promising source for cellular reprogramming for replacing lost pancreatic β cells in diabetes. Gut enterochromaffin cells can be converted to insulin-producing cells by forkhead box O1 (FoxO1) ablation, but their numbers are limited. In this study, we report that insulin-immunoreactive cells with Paneth/goblet cell features are present in human fetal intestine. Accordingly, lineage-tracing experiments show that, upon genetic or pharmacologic FoxO1 ablation, the Paneth/goblet lineage can also undergo conversion to the insulin lineage. We designed a screening platform in gut organoids to accurately quantitate β-like cell reprogramming and fine-tune a combination treatment to increase the efficiency of the conversion process in mice and human adult intestinal organoids. We identified a triple blockade of FOXO1, Notch, and TGF-β that, when tested in insulin-deficient streptozotocin (STZ) or NOD diabetic animals, resulted in near normalization of glucose levels, associated with the generation of intestinal insulin-producing cells. The findings illustrate a therapeutic approach for replacing insulin treatment in diabetes.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.anbehav.2010.01.015 Byline: Jin-Won Lee (a), Yun-Kyoung Lee (b), Ben J. Hatchwell (a) Abstract: Dispersal is a key factor affecting the dynamics and genetic structure of populations. Patterns of natal dispersal vary widely depending on the selection pressures that each species encounters, but the underlying factors determining this variation are poorly understood. We studied the pattern of natal dispersal in a small passerine, the vinous-throated parrotbill, Paradoxornis webbianus, using both direct ringing data and indirect genetic methods. The social structure of this species is characterized by group living without apparent territorial behaviour. The dispersal rate of juveniles from their natal groups was moderate (about 40%) and dispersal distance was short, most individuals moving to neighbouring flocks. Sibling groups that included both sexes usually dispersed or were philopatric together so that they were found in the same winter flock where pairing occurs. Thus, the avoidance of inbreeding or intrasexual competition among siblings appears not to affect natal dispersal in this species. Instead, our results suggest that the benefits of dispersing in groups and/or selection of kin structure within social groups via kin-selected reproductive benefits may promote the observed dispersal pattern: sibling associations without separation of the sexes. This behaviour may have important implications for the kin structure of populations and the evolution of sociality. Author Affiliation: (a) Department of Animal and Plant Sciences, University of Sheffield, U.K. (b) Ecology Research Department, National Institute of Environment Research, Republic of Korea Article History: Received 29 September 2009; Revised 5 November 2009; Accepted 19 January 2010 Article Note: (miscellaneous) MS. number: 09-00644

Calculations of the polarizabilities and hyperpolarizabilities of donor-substituted triphenylmethane dyes which are octupolar molecules are undertaken. The nonlinear optical properties of these molecules are described using the four-state model of an octupolar molecule. A strong donor increases the charge-transfer character of the ground state and also increases the molecular polarizability and first hyperpolarizability of the octupolar molecule.