Indoor radon risk associated to post-tectonic biotite granites from Vila Pouca de Aguiar pluton, northern Portugal.

At Vila Pouca de Aguiar area, northern Portugal, crops out a post-tectonic Variscan granite pluton, related with the Régua-Vila Real-Verín fault zone, comprising three types of biotite granites. Among these granites, PSG granite yield the highest average contents of U, probably due to its enrichment in accessory U-bearing minerals such as zircon. In the proximity of faults and joints, these granites are often affected by different degrees of hydrothermal alteration, forming reddish altered rocks, commonly known as "episyenites". These altered rocks are probably associated to the occurrence of hydrothermal processes, which led to uranium enrichment in the most advanced stages of episyenitization. In these granites, both average gamma absorbed dose rates in outdoor and indoor air are higher than those of the world average. Furthermore, even in the worst usage scenario, all these granites can be used as a building material, since their annual effective doses are similar to the limit defined by the European Commission. The geometric mean of radon activity of 91 dwellings located at the Vila Pouca de Aguiar pluton is 568Bqm(-3), exceeding that of other northern Portuguese granites. Measurements carried out during a winter season, indicate that 62.6% of the analysed dwellings yield higher indoor radon average values than the Portuguese legislation limit (400Bqm(-3)), and annual effective doses due higher than the world's average value (1.2mSvy(-1)). The interaction of geogenic, architectural and anthropogenic features is crucial to explain the variance in the geometric mean of radon activity of dwellings from Vila Pouca de Aguiar pluton, but the role of geologic faults is probably the most important decisive factor to increase the indoor radon concentration in dwellings. Hence, the development of awareness campaigns in order to inform population about the incurred radiological risks to radon exposure are highly recommended for this specific area.

Parp mutations protect against mitochondrial dysfunction and neurodegeneration in a PARKIN model of Parkinson's disease.

The co-enzyme nicotinamide adenine dinucleotide (NAD(+)) is an essential co-factor for cellular energy generation in mitochondria as well as for DNA repair mechanisms in the cell nucleus involving NAD(+)-consuming poly (ADP-ribose) polymerases (PARPs). Mitochondrial function is compromised in animal models of Parkinson's disease (PD) associated with PARKIN mutations. Here, we uncovered alterations in NAD(+) salvage metabolism in Drosophila parkin mutants. We show that a dietary supplementation with the NAD(+) precursor nicotinamide rescues mitochondrial function and is neuroprotective. Further, by mutating Parp in parkin mutants, we show that this increases levels of NAD(+) and its salvage metabolites. This also rescues mitochondrial function and suppresses dopaminergic neurodegeneration. We conclude that strategies to enhance NAD(+) levels by administration of dietary precursors or the inhibition of NAD(+)-dependent enzymes, such as PARP, that compete with mitochondria for NAD(+) could be used to delay neuronal death associated with mitochondrial dysfunction.

Activation of multiple interleukin-1beta converting enzyme homologues in cytosol and nuclei of HL-60 cells during etoposide-induced apoptosis.

Recent genetic and biochemical studies have implicated cysteine-dependent aspartate-directed proteases (caspases) in the active phase of apoptosis. In the present study, three complementary techniques were utilized to follow caspase activation during the course of etoposide-induced apoptosis in HL-60 human leukemia cells. Immunoblotting revealed that levels of procaspase-2 did not change during etoposide-induced apoptosis, whereas levels of procaspase-3 diminished markedly 2-3 h after etoposide addition. At the same time, cytosolic peptidase activities that cleaved DEVD-aminotrifluoromethylcoumarin and VEID-aminomethylcoumarin increased 100- and 20-fold, respectively; but there was only a 1. 5-fold increase in YVAD-aminotrifluoromethylcoumarin cleavage activity. Affinity labeling with N-(Nalpha-benzyloxycarbonylglutamyl-Nepsilon-biotin yllysyl)aspartic acid [(2,6-dimethylbenzoyl)oxy]methyl ketone indicated that multiple active caspase species sequentially appeared in the cytosol during the first 6 h after the addition of etoposide. Analysis on one- and two-dimensional gels revealed that two species comigrated with caspase-6 and three comigrated with active caspase-3 species, suggesting that several splice or modification variants of these enzymes are active during apoptosis. Polypeptides that comigrate with the cytosolic caspases were also labeled in nuclei of apoptotic HL-60 cells. These results not only indicate that etoposide-induced apoptosis in HL-60 cells is accompanied by the selective activation of multiple caspases in cytosol and nuclei, but also suggest that other caspase precursors such as procaspase-2 are present but not activated during apoptosis.