Drosophila orthologue of WWOX, the chromosomal fragile site FRA16D tumour suppressor gene, functions in aerobic metabolism and regulates reactive oxygen species

Common chromosomal fragile sites FRA3B and FRA16D are frequent sites of DNA instability in cancer, but their contribution to cancer cell biology is not yet understood. Genes that span these sites (FHIT and WWOX, respectively) are often perturbed (either increased or decreased) in cancer cells and both are able to suppress tumour growth. While WWOX has some tumour suppressor characteristics, its normal role and functional contribution to cancer has not been fully determined. We find that a significant proportion of Drosophila Wwox interactors identified by proteomics and microarray analyses have roles in aerobic metabolism. Functional relationships between Wwox and either CG6439/isocitrate dehydrogenase (Idh) or Cu–Zn superoxide dismutase (Sod) were confirmed by genetic interactions. In addition, altered levels of Wwox resulted in altered levels of endogenous reactive oxygen species. Wwox (like FHIT) contributes to pathways involving aerobic metabolism and oxidative stress, providing an explanation for the ‘non-classical tumour suppressor’ behaviour of WWOX. Fragile sites, and the genes that span them, are therefore part of a protective response mechanism to oxidative stress and likely contributors to the differences seen in aerobic glycolysis (Warburg effect) in cancer cells

A scaling theory for the size distribution of emitted dust aerosols suggests climate models underestimate the size of the global dust cycle

Mineral dust aerosols impact Earth’s radiation budget through interactions with clouds, ecosystems, and radiation, which constitutes a substantial uncertainty in understanding past and predicting future climate changes. One of the causes of this large uncertainty is that the size distribution of emitted dust aerosols is poorly understood. The present study shows that regional and global circulation models (GCMs) overestimate the emitted fraction of clay aerosols (< 2 μm diameter) by a factor of ∼2–8 relative to measurements. This discrepancy is resolved by deriving a simple theoretical expression of the emitted dust size distribution that is in excellent agreement with measurements. This expression is based on the physics of the scale-invariant fragmentation of brittle materials, which is shown to be applicable to dust emission. Because clay aerosols produce a strong radiative cooling, the overestimation of the clay fraction causes GCMs to also overestimate the radiative cooling of a given quantity of emitted dust. On local and regional scales, this affects the magnitude and possibly the sign of the dust radiative forcing, with implications for numerical weather forecasting and regional climate predictions in dusty regions. On a global scale, the dust cycle in most GCMs is tuned to match radiative measurements, such that the overestimation of the radiative cooling of a given quantity of emitted dust has likely caused GCMs to underestimate the global dust emission rate. This implies that the deposition flux of dust and its fertilizing effects on ecosystems may be substantially larger than thought

Synthesis and antibiotic activity of some &#946;-Carboline alkaloids

Nine &#946;-carboline alkaloids were synthetized and screened for antibiotic activity. Six of the compounds testes showed inhibitory activity against one or more of the microorganisms assayed