The Wnt-dependent signaling pathways as target in oncology drug discovery

Our current understanding of the Wnt-dependent signaling pathways is mainly based on studies performed in a number of model organisms including, Xenopus, Drosophila melanogaster, Caenorhabditis elegans and mammals. These studies clearly indicate that the Wnt-dependent signaling pathways are conserved through evolution and control many events during embryonic development. Wnt pathways have been shown to regulate cell proliferation, morphology, motility as well as cell fate. The increasing interest of the scientific community, over the last decade, in the Wnt-dependent signaling pathways is supported by the documented importance of these pathways in a broad range of physiological conditions and disease states. For instance, it has been shown that inappropriate regulation and activation of these pathways is associated with several pathological disorders including cancer, retinopathy, tetra-amelia and bone and cartilage disease such as arthritis. In addition, several components of the Wnt-dependent signaling pathways appear to play important roles in diseases such as Alzheimer’s disease, schizophrenia, bipolar disorder and in the emerging field of stem cell research. In this review, we wish to present a focused overview of the function of the Wnt-dependent signaling pathways and their role in oncogenesis and cancer development. We also want to provide information on a selection of potential drug targets within these pathways for oncology drug discovery, and summarize current data on approaches, including the development of small-molecule inhibitors, that have shown relevant effects on the Wnt-dependent signaling pathways

Affective technologies of welfare deterrence in Australia and the United Kingdom

Across the political spectrum of different historical periods, welfare deterrence has shaped social security and immigration policy in both Australia and the United Kingdom. Deterrence discourages access to state welfare through the production and mobilization of negative affect to deter specific groups from claiming state support, and by crafting public affect (of fear and disgust) about these target populations in order to garner consent for punitive policies. In this paper, we argue that deterrence works as a human technology where the crafting of negative affect operates as a technology of statecraft. Through critical juxtaposition and multiple genealogies of deterrence, this paper meshes time and space, and colony/colonizer and metropole, to show the historical and contemporary connectivity of the affective nature of deterrence. We identify five main operations that produce the ‘feel’ of deterrence: stigmatization by design, destitution by design, deterrent architecture, the control of movement, and the centrality of labour; as well as tracing the political economy of deterrence

Harvests of shame: enduring unfree labour in twentieth century United States, 1933-1964

This article reframes the discussion on vulnerable and exploited agricultural labour in twentieth-century United States using the overarching category of unfree labour. In order to do so, it bridges two usually distinct historiographies by linking the phenomenon of ‘peonage’ during the New Deal, with the one of immigrant contract labour southern Florida, under the H2 visa. Archival research on the practices at the US Sugar Corporation in southern Florida exemplifies this link. This article draws on federal archives, government proceedings, papers of political activists and legal and labour scholarship to argue: firstly, that unfree labour has been an enduring feature of agricultural labour relations at regional level during the twentieth century, through both a transmission and a transformation of practice that had their origin in the control of black emancipated labour; secondly, that the introduction of guest workers under the H2 and Bracero programme meant a modernization in the practices of unfree labour, pivoting on the lack of citizenship rights, racial discrimination, debt at home, and threat of deportation; and, finally, that the failure to recognise forms of legal and economic deprivation and coercion as unfree labour has hurt the ability of the United States to enforce protection of human rights at home