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Pan‐cyclin‐dependent‐kinase (CDK) inhibitors are a new class of targeted therapies that can act on multiple CDKs, with dinaciclib being one of the most promising compounds. Although used as a monotherapy, an interesting approach could be to combine it with radiotherapy. Here, we show that dinaciclib increases radiosensitivity in some experimental models of lung and colon cancer (A549 or HCT 116) but not in others (H1299 or HT‐29). Dinaciclib did not alter serine‐protein kinase ATM signalling or cell cycle profiling after ionising‐radiation exposure, which have been described for other CDK inhibitors. Interestingly, in terms of apoptosis, although the combination renders a clear increase, no potentiation of the ionising‐radiation‐induced apoptosis was observed. Mechanistically, inhibition of CDK12 by dinaciclib diminishes BRCA1 expression, which decreases homologous recombination (HR) and probably promotes the nonhomologous end joining repair process (NHEJ), which ultimately promotes the induction of ionising‐radiation‐associated cellular senescence in a TP53‐dependent manner, explaining the lack of effect observed in some experimental models. In conclusion, our report proposes a molecular mechanism, based on the signalling axis CDK12–BRCA1, involved in this newly identified therapeutic effect of dinaciclib, although other players implicated in HR should not be discarded. In addition, our data provide a rationale for more selective and personalised chemo/radiotherapy treatment according to the genetic background of the tumour. [ABSTRACT FROM AUTHOR]

ABSTRACT The Intag cloud forest region of northwestern Ecuador is characterized by exceptional biodiversity, large known and unknown deposits of copper and other valuable minerals, and a high level of environmental awareness and concern among the human population. Its 1000 km of rivers and streams are essential for household use, crop irrigation, livestock production and sustaining unique ecosystems. However, no published data exist on water quality in the region. This study characterizes water quality in five river systems in Intag and relates it to land use (protected forest, agriculture/pasture, urban development or mining) upstream of the sampling point. Additionally, we sampled 15 community water supply systems. Parameters measured included turbidity, temperature, dissolved oxygen, pH, faecal indicator bacteria (FIB), nitrate, phosphate, ammonium, Ni, Mn, Cu, Zn, Cd, Pb, As, Cr, discharge and aquatic invertebrate diversity. Significant differences in pH, aquatic invertebrate diversity, and the concentrations of FIB, nutrients and dissolved metals were observed between land use groups. Forested streams consistently had the lowest pollutant concentrations, whereas those flowing past population centres or mining areas showed the greatest impairment. Elevated As concentrations were observed in association with abandoned mining boreholes, hot springs and wastewater discharges. FIB, nutrient and metal concentrations in water systems were similar to those in forested streams, indicating that these systems maintain water in an unpolluted condition. To preserve and enhance Intag's generally good water quality, we recommend installing wastewater treatment systems in larger towns and approaching all mining activity, including exploration, with extreme caution. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]