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

"Looking all lost towards a Cook's guide for beauty”: the art of literature and the lessons of the guidebook in modernist writing

This article explores the impact of the guidebook, especially the Baedeker series, on modernist literary culture. It argues that the guidebook is a literary phenomenon in its own right and that, as such, it attracts special attention from those engaged in defending and/or extending the category of literature as part of a modernist agenda. In particular, modernist writers are concerned as to whether the guidebook counts as a form of literature and, if so, what this means for the more familiar forms seen in their own essays, fiction and travelogues. What might the invention of the star system to rank scenes and monuments mean for the future of art criticism? How might the guidebook help or hinder the traveller in his/her pursuit of the beautiful or the picturesque? What does recourse to the guidebook reveal about the taste and education of the traveller? And, more pointedly still, what kind and quality of writing is the guidebook itself? This article surveys the extent of modernism's interest in the guidebook, both as a noteworthy new form and as a form modernist writers adapted for use in their own books, before turning in detail to commentary on the guidebook by E.M. Forster, Ernest Hemingway, H.D. and Virginia Woolf. In conclusion, it finds that the guidebook in modernism is very rarely just that. Instead, the guidebook finds unexpected affinities with modernism in its attempt to “modernise” literature – to make it more rational, more totalising and, in the eyes of its critics, less able to discriminate.This is an Accepted Manuscript of an article published by Taylor & Francis in Studies in Travel Writing on 4th March 2015, available online: http://wwww.tandfonline.com/10.1080/13645145.2014.994924

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

Transurethral resection of the ejaculatory ducts for treating ejaculatory symptoms.

OBJECTIVES: To report our experience with transurethral resection of the ejaculatory ducts (TURED) in infertile men with symptomatic ejaculatory duct obstruction (EDO). PATIENTS AND METHODS: Before surgery, all patients complained of a decrease in the volume of their ejaculate, 14 of 15 had a non-projectile ejaculation, nine had a genitourinary infection necessitating antibiotic treatment, and five had pain with orgasm. The mean ejaculate volume and total motile sperm count was 1.1 mL and 8.1 million sperm per ejaculate. After surgery, at a mean follow-up of 2 months, 10 men reported having projectile ejaculation, and eight reported a marked improvement in their sensation of orgasm. Overall, 14 men reported a subjective improvement in their ejaculation. The average postoperative ejaculate volume was 2.3 mL and the total motile sperm count was 38.1 million per ejaculate. CONCLUSIONS: Men with symptomatic EDO who underwent TURED showed improvements in their ejaculation, sensation of orgasm, semen analysis values and fertility