Smac Mimetics and TNFalpha: A Dangerous Liaison?

Inhibitor of apoptosis proteins (IAPs) such as XIAP, cIAP1, and cIAP2 are upregulated in many cancer cells. It has been thought that small-molecule mimetics of Smac, an endogenous IAP antagonist, might potentiate apoptosis in cancer cells by promoting caspase activation. However, three recent papers, two in Cell (Vince et al., 2007; Varfolomeev et al., 2007) and one in Cancer Cell (Petersen et al., 2007), now report that Smac mimetics primarily kill cancer cells via a different mechanism, the induction of autoubiquitination and degradation of cIAPs, which culminates in TNFalpha-mediated cell death

Talking about trees: the territorial classification of native forests in the Argentinian Chaco

Deforestation represents an important contributor to climate change. For this reason, identifying conditions that enable the adoption of policies halting or reversing this process is crucial to avoid catastrophic climate change. The Argentinian Gran Chaco is a hotspot of deforestation, mainly due to the expansion of capital-intensive agriculture. In Argentina, the introduction of the national forest law (NFL) represents an important step to protect the remaining forests. However, in the Chaco ecoregion, the implementation of the NFL by the different provinces is extremely heterogeneous. Previous research has provided rich descriptions of the dynamics behind the implementation of the NFL. Yet this research, mainly based on qualitative approaches, does not allow for a systematic analysis of the conditions leading to more or less stringent implementations of the NFL. To address this gap, we first combine the socio-ecological systems framework with historical materialism to generate a plausible hypothesis for the heterogeneous implementation of the NFL across the 12 different provinces of the Argentinian Chaco. Specifically, we hypothesise that it is the differences in contextual factors (i.e. differences in forest cover), material/economic conditions (i.e. presence and extent of capital-intensive agriculture) and the strength of pro- and anti-deforestation coalitions, which lead to a heterogeneous territorial classification of native forests across the various provinces. Subsequently, we test the hypothesis by developing thorough case studies via qualitative comparative analysis. This approach allows us to study in a more systematic way the reasons for the observed institutional heterogeneity. The results show that the proportion of native forests characterised as of low conservation value reflects both the environmental context (i.e. the extent of native forests) as well as the material/economic conditions (i.e. the extent of capital-intensive agriculture) and the presence of strong pro-deforestation cultures, expressed via pro-deforestation coalitions

Superadiabatic dynamical density functional study of Brownian hard-spheres in time-dependent external potentials

Superadiabatic dynamical density functional theory (superadiabatic-DDFT), a first-principles approach based on the inhomogeneous two-body correlation functions, is employed to investigate the response of interacting Brownian particles to time-dependent external driving. Predictions for the superadiabatic dynamics of the one-body density are made directly from the underlying interparticle interactions, without need for either adjustable fit parameters or simulation input. The external potentials we investigate have been chosen to probe distinct aspects of structural relaxation in dense, strongly interacting liquid states. Nonequilibrium density profiles predicted by the superadiabatic theory are compared with those obtained from both adiabatic DDFT and event-driven Brownian dynamics simulation. Our findings show that superadiabatic-DDFT accurately predicts the time-evolution of the one-body density