Respuesta de las células HeLa y EA.hy926 al estrés por hipoxia y radiación ionizante a través de la vía JAK/STAT y la supervivencia celular

El comportamiento biológico de las células cancerosas es influenciado por el microambiente en el que se desarrollan y en este, factores como la angiogénesis o el estímulo de agentes estresores como la hipoxia, se han considerado críticos para su evolución y manejo terapéutico. Uno de los mecanismos moleculares implicados en la respuesta celular frente a estímulos estresores es la activación de vías de señalización intracelulares; en este estudio, se evaluó el estado de la vía JAK/STAT y en ella la expresión/activación de la proteína STAT3 en la línea tumoral (HeLa) y endotelial (EA.hy926), sometidas a hipoxia física y química con mesilato de deferoxamina durante 2, 6 y 24 horas. Adicionalmente, al considerar la importancia de la hipoxia como un agente modificador de la respuesta en el manejo del cáncer utilizando radiaciones ionizantes, se construyeron curvas de supervivencia celular que permitieron evaluar el comportamiento celular frente a estos estímulos. El presente estudio resalta la importancia de la hipoxia como un estímulo que modifica la activación de la proteína STAT3 y la supervivencia de células irradiadas en las dos líneas estudiadas.

The environmental impact of civil conflict : the deforestation effect of paramilitary expansion in Colombia

Despite a growing body of literature on how environmental degradation can fuel civil war, the reverse effect, namely that of conflict on environmental outcomes, is relatively understudied. From a theoretical point of view this effect is ambiguous, with some forces pointing to pressures for environmental degradation and some pointing in the opposite direction. Hence, the overall effect of conflict on the environment is an empirical question. We study this relationship in the case of Colombia. We combine a detailed satellite-based longitudinal dataset on forest cover across municipalities over the period 1990-2010 with a comprehensive panel of conflict-related violent actions by paramilitary militias. We first provide evidence that paramilitary activity significantly reduces the share of forest cover in a panel specification that includes municipal and time fixed effects. Then we confirm these findings by taking advantage of a quasi-experiment that provides us with an exogenous source of variation for the expansion of the paramilitary. Using the distance to the region of Urab´a, the epicenter of such expansion, we instrument paramilitary activity in each cross-section for which data on forest cover is available. As a falsification exercise, we show that the instrument ceases to be relevant after the paramilitaries largely demobilized following peace negotiations with the government. Further, after the demobilization the deforestation effect of the paramilitaries disappears. We explore a number of potential mechanisms that may explain the conflict-driven deforestation, and show evidence suggesting that paramilitary violence generates large outflows of people in order to secure areas for growing illegal crops, exploit mineral resources, and engage in extensive agriculture. In turn, these activities are associated with deforestation.

The use of insect cells to identify potent and selective inhibitors of the replication of the Dengue and Chikungunya viruses and unravel their molecular mechanism of action

Dengue and Chikungunya viruses cause the most important arthropod-borne viral infections for humans. These viruses are predominant in tropical and subtropical regions. In addition, these viruses are predominant in tropical and subtropical regions. Dengue mortality rate is around 1.2 to 3.5% and deaths due to chikungunya fever are around 1 in 1000; however, half of chikungunya-infected patients evolve into a chronic state that can persist for months up to years. There are no antiviral drugs available for DENV and CHIKV treatment and prevention. Moreover, vector control strategies have failed so far. Thus, the development of potent inhibitors for a broad spectrum of RNA viruses is urgently needed. We established and characterized a new embryonic insect cell line from Culex quinquefasciatus mosquito. Also we established the flaviviruses and alphavirus replication, both in C6/36 and Lulo insect cell lines, as well as in Vero cell line. In addition we carried out a reference compound library and reference panel of assays and data for DENV, which provides a benchmark for further studies. During this study, a panel of 9 antiviral molecules, with proven in vitro anti-dengue virus activity and that act at different stages of the DENV life cycle, was selected. Finally, Favipiravir or T-705, was identified as inhibitor in vitro and in vivo of alphaviruses and the mutation K291R in nsP4, which is responsible of the polymerase activity, was found as the mode of action in CHIKV. Interestingly, lysine in motif F1 is also highly conserved in positive-stranded RNA viruses and this might explain the broad spectrum of T-705 antiviral activity.