BackgroundCannabinoids represent unique compounds for treating tumors, including astrocytomas. Whether CB1 and CB2 receptors mediate this therapeutic effect is unclear.Principal FindingsWe generated astrocytoma subclones that express set levels of CB1 and CB2, and found that cannabinoids induce apoptosis only in cells expressing low levels of receptors that couple to ERK1/2. In contrast, cannabinoids do not induce apoptosis in cells expressing high levels of receptors because these now also couple to the prosurvival signal AKT. Remarkably, cannabinoids applied at high concentration induce apoptosis in all subclones independently of CB1, CB2 and AKT, but still through a mechanism involving ERK1/2.SignificanceThe high expression level of CB1 and CB2 receptors commonly found in malignant astrocytomas precludes the use of cannabinoids as therapeutics, unless AKT is concomitantly inhibited, or cannabinoids are applied at concentrations that bypass CB1 and CB2 receptors, yet still activate ERK1/2.
Abstract. The interactions between climate, vegetation and fire can strongly influence
the future trajectories of vegetation in Earth system models. We evaluate the
relationships between tropical climate, vegetation and fire in the global
vegetation model JSBACH, using a simple fire scheme and the complex fire
model SPITFIRE with the aim to identify potential for model improvement. We
use two remote-sensing products (based on MODIS and Landsat) in different
resolutions to assess the robustness of the obtained observed relationships.
We evaluate the model using a multivariate comparison that allows us to focus
on the interactions between climate, vegetation and fire and test the
influence of land use change on the modelled patterns.
Climate–vegetation–fire relationships are known to differ between
continents; we therefore perform the analysis for each continent separately. The observed relationships are
similar in the two satellite data sets, but maximum tree cover is reached at
higher precipitation values for coarser resolution. This shows that the
spatial scale of models and data needs to be consistent for meaningful
comparisons. The model captures the broad spatial patterns with regional
differences, which are partly due to the climate forcing derived from an
Earth system model. Compared to the simple fire scheme, SPITFIRE strongly
improves the spatial pattern of burned area and the distribution of burned
area along increasing precipitation. The correlation between precipitation
and tree cover is higher in the observations than in the largely climate-driven vegetation model, with both fire models. The multivariate comparison
identifies excessive tree cover in low-precipitation areas and a too-strong relationship between high fire occurrence and low tree cover for the
complex fire model. We therefore suggest that drought effects on tree cover
and the impact of burned area on tree cover or the adaptation of trees to
fire can be improved. The observed variation in the relationship between precipitation and maximum
tree cover between continents is higher than the simulated one. Land use
contributes to the intercontinental differences in fire regimes with SPITFIRE
and strongly overprints the modelled multimodality of tree cover with
SPITFIRE. The multivariate model–data comparison used here has several
advantages: it improves the attribution of model–data mismatches to model
processes, it reduces the impact of biases in the meteorological forcing on
the evaluation and it allows us to evaluate not only a specific target variable
but also the interactions.
The structural dynamics of short-pulse laser irradiated surfaces and nano-structures has been studied with nm spatial and ultrafast temporal resolution by means of single-shot coherent XUV-scattering techniques. The experiments allowed us to time-resolve the formation of laser-induced periodic surface structures, and to follow the expansion and disintegration of nano-objects during laser ablation.
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