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The identification of therapeutic approaches to improve response to platinum-based therapies is an urgent need for ovarian carcinoma. Deubiquitinases are a large family of ubiquitin proteases implicated in a variety of cellular functions and may contribute to tumor aggressive features through regulation of processes such as proliferation and cell death. Among the subfamily of ubiquitin-specific peptidases, USP8 appears to be involved in modulation of cancer cell survival by still poorly understood mechanisms. Thus, we used ovarian carcinoma cells of different histotypes, including cisplatin-resistant variants with increased survival features to evaluate the efficacy of molecular targeting of USP8 as a strategy to overcome drug resistance/modulate cisplatin response. We performed biochemical analysis of USP8 activity in pairs of cisplatin-sensitive and -resistant cells and found increased USP8 activity in resistant cells. Silencing of USP8 resulted in decreased activation of receptor tyrosine kinases and increased sensitivity to cisplatin in IGROV-1/Pt1 resistant cells as shown by colony forming assay. Increased cisplatin sensitivity was associated with enhanced cisplatin-induced caspase 3/7 activation and apoptosis, a phenotype also observed in cisplatin sensitive cells. Increased apoptosis was linked to FLIPL decrease and cisplatin induction of caspase 3 in IGROV-1/Pt1 cells, cisplatin-induced claspin and survivin down-regulation in IGROV-1 cells, thereby showing a decrease of anti-apoptotic proteins. Immunohistochemical staining on 65 clinical specimens from advanced stage ovarian carcinoma indicated that 40% of tumors were USP8 positive suggesting that USP8 is an independent prognostic factor for adverse outcome when considering progression free survival as a clinical end-point. Taken together, our results support that USP8 may be of diagnostic value and may provide a therapeutic target to improve the efficacy of platinum-based therapy in ovarian carcinoma. Funding Agencies|Associazione Italiana per la Ricerca sul Cancro (AIRC IG); [24725]

Mauritius is often considered a ‘success story’ to be read for salutary purposes by other small island developing states (SIDS). While it does share broadly similar attributes with many other SIDS, and acts in unison with other SIDS in international fora, local histories, cultures, geography and location invariably lead to significant differences in developmental trajectories. This paper presents an assessment of Mauritian history in order to explore the contemporary threats and opportunities that face the island in its contemporary quest to transform the island into Maurice Ȋle Durable. Rather than offering Mauritius as a guide to other SIDS, it presents a useful case study of the tension between establishing social equity and carving out a functional role within the global economy.

Element export rates from the drainage area of nine harvested, nine burnt, and 16 reference Boreal Shield lake basins in Haute-Mauricie, Québec, were estimated for the 3 years following harvesting or fires. Export rates from the drainage area of the basins were evaluated using lake sampling surveys, estimated hydrological budgets, and estimated nutrient retention during lake transit. Increases in K+, total N, and total P export rates were similar between harvested and burnt drainage areas. However, harvested drainage areas exported more dissolved organic C, while burnt drainage areas exported more Mg2+, NO3-, and SO42-. Potassium cumulative losses in runoff during the 3 years of the study were of a similar magnitude as volatilization losses during fires and corresponded to ~33% of the losses by biomass removal during harvesting. While the increased export rates for N and P following fires or harvesting represented negligible losses of nutrients for the forest, they were important supplementary inputs to lakes. The differences in element export rates observed between harvested and burnt drainage areas indicate that these disturbances have different impacts on biogeochemical cycles in the Boreal Shield forest.