ABCB4 missense mutations D243A, K435T, G535D, I490T, R545C, and S978P significantly impair the lipid floppase and likely predispose to secondary pathologies in the human population

EJA was funded by Barts and the London Charity (award 458/1495). MN was funded by a Medical Research Council Centenary Award

Inter Governmental Organizations and the Kantian Peace: A Network Perspective

The authors use network analysis to argue that the main contribution of intergovernmental organizations (IGOs) to international stability is not necessarily their direct and individual impact, because generally IGOs are institutionally weak. Rather, membership of IGOs creates network ties between states, allowing them, either individually or collectively, to intervene more effectively in latent conflicts. The IGO network also provides direct and indirect communication channels, where indirect links can act as partial substitutes for direct diplomatic ties. Empirically, the authors apply these ideas to the extensive network of international linkages created in the post?World War II period. They demonstrate that indirect links do indeed matter and that they substitute for more direct diplomatic ties. Furthermore, these effects are not limited to ties created by IGOs with specific security functions

Age-related defects in B lymphopoiesis underlie the myeloid dominance of adult leukemia

Reduced lymphopoiesis during aging contributes to declines in immunity, but little consideration has been given to its effect on the development of hematologic disease. This report demonstrates that age-related defects in lymphopoiesis underlie the myeloid dominance of adult leukemia. Using a murine model of chronic myeloid leukemia, an adult-onset malignancy that arises from transformation of hematopoietic stem cells by the BCR-ABLP210 oncogene, we demonstrate that young bone marrow (BM) cells that were transformed with BCR-ABLP210 initiated both a myeloproliferative disorder (MPD) and B-lymphoid leukemia, whereas BCR-ABLP210–transformed old BM cells recapitulated the human disease by inducing an MPD with rare lymphoid involvement. In addition, the lesser severity of MPDs initiated from old BCR-ABLP210–transduced BM cells revealed unappreciated defects in aged myeloid progenitors. These data demonstrate that aging affects patterns of leukemogenesis and indicate that the effects of senescence on hematopoiesis are more extensive than previously appreciated