International audienceSince the 1990s, drastic melting of sea ice and continental ice in the Arctic region, triggered by global warming, has caused substantial freshening of the Arctic Ocean. While several studies attempted to quantify the magnitude of this freshening, its consequences on primary producers remain poorly documented. In this study, we evaluate the impact of the freshwater content (FWC) of the upper Arctic Ocean on phytoplankton across the Pacific sector, from the Bering Strait (65°N) to the North Pole (86°N), during summer 2008. We performed statistical analyses on the physical, biogeochemical and biological data acquired during the CHINARE 2008 cruise to investigate the effect of sea-ice melting on the Arctic phytoplankton. We found that the strong freshening observed in the Canada Basin had a negative impact on primary producers as a result of the deepening of the nitracline and the establishment of a subsurface chlorophyll maximum (SCM). In contrast, regions with lower freshening, such as the Chukchi shelf and the marginal ice zone (MIZ) over the Chukchi Borderland, exhibited a shallower nitracline sustaining relatively high primary production and biomass. Our results imply that the predicted increase freshening in future years will likely cause the Arctic deep basin to become more oligotrophic because of weaker surface nutrient renewal from the subsurface ocean, despite higher light penetration

The epithelial to mesenchymal transition (EMT) that occurs during embryonic development has begun to attract attention as a potential mechanism for tumor cell metastasis. Snail is a well-known Zn-finger transcription factor that promotes EMT by repressing E-cadherin expression. It is known that Snail is phosphorylated by GSK3b and degraded by b-TrCP-mediated ubiquitination. Here we described another protein kinase, CK1, whose phosphorylation of Snail is required for the subsequent GSK3b phosphorylation. Specific inhibition or depletion of CK1e inhibits the phosphorylation and degradation of Snail and promotes cell migration, suggesting a central role of CK1e in the EMT process. Furthermore, our study uncovered distinct roles and steps of Snail phosphorylation by CK1e and GSK3b. Taken together, we identified CK1e as a new component of the Snail-mediated EMT process, providing insight into the mechanism of human cancer metastasis.

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p53 is frequently mutated by genetic alternation or suppressed by various kinds of cellular signaling pathways in human cancers. Recently, we have revealed that p53 is suppressed and eliminated from cells by direct binding with oncogenic K-Ras-induced Snail. On the basis of the fact, we generated specific inhibitors against p53-Snail binding (GN25 and GN29). These chemicals can induce p53 expression and functions in K-Ras-mutated cells. However, it does not show cytotoxic effect on normal cells or K-Raswild-type cells. Moreover, GN25 can selectively activate wild-type p53 in p53 WT/MT cancer cells. But single allelic mt p53 containing cell line, Panc-1, does not respond to our chemical. In vivo xenograft test also supports the antitumor effect of GN25 in K-Ras-mutated cell lines. These results suggest that our compounds are strong candidate for anticancer drug against K-Ras-initiated human cancers including pancreatic and lung cancers.

Intramolecular excimer formation of 1,3-di(1-pyrenyl)propane (Py-3-Py) and fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) were used to evaluate the effect of ethanol on the rate and range of the lateral mobility and the range of the rotational mobility of bulk bilayer structures of the plasma membrane vesicles (ATCC-PMV) isolated from cultured hybridoma cells (ATCC TIB 216). In a concentration-dependent manner, ethanol increased the excimer to monomer fluorescence intensity ratio (I'/I) of Py-3-Py in the ATCC-PMV and decreased the anisotropy (r), limiting anisotropy (r infinity) and order parameter (S) of DPH in the ATCC-PMV. This indicates that ethanol increased both the lateral and rotational mobility of the probes in the ATCC-PMV. Selective quenching of DPH by trinitrophenyl groups was utilized to examine the range of transbilayer asymmetric rotational diffusion of the ATCC-PMV. The anisotropy (r), limiting anisotropy (r infinity) and order parameter (S) of DPH in the inner monolayer were 0.024, 0.032, and 0.069, respectively, greater than calculated for the outer monolayer of the ATCC-PMV. Selective quenching of DPH by trinitrophenyl groups was also used to examine the transbilayer asymmetric effects of ethanol on the range of the rotational mobility of the ATCC-PMV. Ethanol had a greater increasing effect on the range of the rotational mobility of the outer monolayer as compared to the inner monolayer of the ATCC-PMV. It has been proven that ethanol exhibits a selective rather than nonselective fluidizing effect within the transbilayer domains of the ATCC-PMV.