The West African Monsoon Onset: a concise comparison of definitions

The onset of the West African Monsoon (WAM) marks a vital time for local and regional stakeholders. Whilst the seasonal progression of monsoon winds and the related migration of precipitation from the Guinea Coast towards the Soudan/Sahel is apparent, there exist contrasting man-made definitions of what the WAM onset means. Broadly speaking, onset can be analyzed regionally, locally or over a designated intermediate scale. There are at least eighteen distinct definitions of the WAM onset in publication with little work done on comparing observed onset from different definitions or comparing onset realizations across different datasets and resolutions. Here, nine definitions have been calculated using multiple datasets of different metrics at different resolution. It is found that mean regional onset dates are consistent across multiple datasets and different definitions. There is low inter-annual variability in regional onset suggesting that regional seasonal forecasting of the onset provides few benefits over climatology. In contrast, local onsets show high spatial, inter-annual and inter-definition variability. Furthermore it is found that there is little correlation between local onset dates and regional onset dates across West Africa implying a disharmony between regional measures of onset and the experience on a local scale. The results of this study show that evaluation of seasonal monsoon onset forecasts is far from straightforward. Given a seasonal forecasting model, it is possible to simultaneously have a good and bad prediction of monsoon onset simply through selection of onset definition and observational dataset used for comparison

Inhibition of all-TRANS-retinoic acid metabolism by R116010 induces antitumour activity

All-trans-retinoic acid is a potent inhibitor of cell proliferation and inducer of differentiation. However, the clinical use of all-trans-retinoic acid in the treatment of cancer is significantly hampered by its toxicity and the prompt emergence of resistance, believed to be caused by increased all-trans-retinoic acid metabolism. Inhibitors of all-trans-retinoic acid metabolism may therefore prove valuable in the treatment of cancer. In this study, we characterize R116010 as a new anticancer drug that is a potent inhibitor of all-trans-retinoic acid metabolism. In vitro, R116010 potently inhibits all-trans-retinoic acid metabolism in intact T47D cells with an IC50-value of 8.7 nM. In addition, R116010 is a selective inhibitor as indicated by its inhibition profile for several other cytochrome P450-mediated reactions. In T47D cell proliferation assays, R116010 by itself has no effect on cell proliferation. However, in combination with all-trans-retinoic acid, R116010 enhances the all-trans-retinoic acid-mediated antiproliferative activity in a concentration-dependent manner. In vivo, the growth of murine oestrogen-independent TA3-Ha mammary tumours is significantly inhibited by R116010 at doses as low as 0.16 mg kg−1. In conclusion, R116010 is a highly potent and selective inhibitor of all-trans-retinoic acid metabolism, which is able to enhance the biological activity of all-trans-retinoic acid, thereby exhibiting antitumour activity. R116010 represents a novel and promising anticancer drug with an unique mechanism of action

Regional-scale climate-variability synchrony of cholera epidemics in West Africa

BACKGROUND: The relationship between cholera and climate was explored in Africa, the continent with the most reported cases, by analyzing monthly 20-year cholera time series for five coastal adjoining West African countries: Côte d'Ivoire, Ghana, Togo, Benin and Nigeria. METHODS: We used wavelet analyses and derived methods because these are useful mathematical tools to provide information on the evolution of the periodic component over time and allow quantification of non-stationary associations between time series. RESULTS: The temporal variability of cholera incidence exhibits an interannual component, and a significant synchrony in cholera epidemics is highlighted at the end of the 1980's. This observed synchrony across countries, even if transient through time, is also coherent with both the local variability of rainfall and the global climate variability quantified by the Indian Oscillation Index. CONCLUSION: Results of this study suggest that large and regional scale climate variability influence both the temporal dynamics and the spatial synchrony of cholera epidemics in human populations in the Gulf of Guinea, as has been described for two other tropical regions of the world, western South America and Bangladesh

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

Efficacy and tolerance of immune chekpoint inhibitors in EGR, ALK/ROS 1 non small cell lung cancer (NSCLC) : GFPC 03-2016 IMAD study.

International audienc

Disruption of Murine Mus81 Increases Genomic Instability and DNA Damage Sensitivity but Does Not Promote Tumorigenesis

The Mus81-Eme1 endonuclease is implicated in the efficient rescue of broken replication forks in Saccharomyces cerevisiae and Schizosaccharomyces pombe. We have used gene targeting to study the function of the Mus81-Eme1 endonuclease in mammalian cells. Mus81-deficient mice develop normally and are fertile. Surprisingly, embryonic fibroblasts from Mus81(−/−) animals fail to proliferate in vitro. This proliferation defect can be rescued by expression of the papillomavirus E6 protein that promotes degradation of p53. When grown in culture, Mus81(−/−) cells have elevated levels of DNA damage, acquire chromosomal aberrations, and are hypersensitive to agents that generate DNA cross-links. In contrast to the situation in yeast, murine Mus81 is not required for replication restart following camptothecin treatment. Mus81(−/−) mice and cells are hypersensitive to DNA cross-linking agents. Cross-link-induced double-strand break formation is normal in Mus81(−/−) cells, but the resolution of repair intermediates is not. The persistence of Rad51 foci in Mus81(−/−) cells suggests that Mus81 acts at a late step in the repair of cross-link-induced lesions. Despite these defects, Mus81(−/−) mice do not show increased predisposition to lymphoma or any other malignancy in the first year of life