Notch-IGF1 signalling in biliary epithelial cells drives their expansion and inhibits hepatocyte differentiation

[no abstract available

Feminist Reflections on the Scope of Labour Law: Domestic Work, Social Reproduction and Jurisdiction

Drawing on feminist labour law and political economy literature, I argue that it is crucial to interrogate the personal and territorial scope of labour. After discussing the “commodification” of care, global care chains, and body work, I claim that the territorial scope of labour law must be expanded beyond that nation state to include transnational processes. I use the idea of social reproduction both to illustrate and to examine some of the recurring regulatory dilemmas that plague labour markets. I argue that unpaid care and domestic work performed in the household, typically by women, troubles the personal scope of labour law. I use the example of this specific type of personal service relation to illustrate my claim that the jurisdiction of labour law is historical and contingent, rather than conceptual and universal. I conclude by identifying some of the implications of redrawing the territorial and personal scope of labour law in light of feminist understandings of social reproduction

Engineering HIV-Resistant Human CD4+ T Cells with CXCR4-Specific Zinc-Finger Nucleases

HIV-1 entry requires the cell surface expression of CD4 and either the CCR5 or CXCR4 coreceptors on host cells. Individuals homozygous for the ccr5Δ32 polymorphism do not express CCR5 and are protected from infection by CCR5-tropic (R5) virus strains. As an approach to inactivating CCR5, we introduced CCR5-specific zinc-finger nucleases into human CD4+ T cells prior to adoptive transfer, but the need to protect cells from virus strains that use CXCR4 (X4) in place of or in addition to CCR5 (R5X4) remains. Here we describe engineering a pair of zinc finger nucleases that, when introduced into human T cells, efficiently disrupt cxcr4 by cleavage and error-prone non-homologous DNA end-joining. The resulting cells proliferated normally and were resistant to infection by X4-tropic HIV-1 strains. CXCR4 could also be inactivated in ccr5Δ32 CD4+ T cells, and we show that such cells were resistant to all strains of HIV-1 tested. Loss of CXCR4 also provided protection from X4 HIV-1 in a humanized mouse model, though this protection was lost over time due to the emergence of R5-tropic viral mutants. These data suggest that CXCR4-specific ZFNs may prove useful in establishing resistance to CXCR4-tropic HIV for autologous transplant in HIV-infected individuals

A novel series of positive modulators of the AMPA receptor : structure-based lead optimization

Starting from lead compound 1, we demonstrate how x-ray structural data can be used to understand SAR and expediently optimize bioavailability in a novel series of AMPA receptor modulators, furnishing 5 with improved bioavailability and robust in vivo activity