We have recently reported that human melanoma cells express a variety of voltage-gated calcium (Ca(2+) ) channel types, including low-voltage-activated T-type channels that play a significant role in melanoma cell cycle progression. Here, we challenged melanoma metastatic cells with T-type channel blockers of clinical use and found a dual effect on cell viability: (i) a reduction in the proliferation rate, through a halt in the progression to the G1 -S phase; and (ii) a promotion of cell death that was partially dependent on the activation of caspases. An in-depth analysis of the death process showed that the apoptotic pathway is preceded by endoplasmic reticulum stress and the subsequent inhibition of the basal macroautophagy which is active in these cells. The effects of pharmacological blockers on Ca(2+) homeostasis, autophagy, and cell death were mimicked by T-type channel gene silencing. These results provide the basis for a new pharmacological and/or gene silencing approach toward tackling melanoma metastasis.

A recent paper published in the journal Food and Chemical Toxicology presents the results of a long-term toxicity study related to a widely-used commercial herbicide (Roundup™) and a Roundup-tolerant genetically modified variety of maize, concluding that both the herbicide and the maize varieties are toxic. Here we discuss the many errors and inaccuracies in the published article resulting in highly misleading conclusions, whose publication in the scientific literature and in the wider media has caused damage to the credibility of science and researchers in the field. We and many others have criticized the study, and in particular the manner in which the experiments were planned, implemented, analyzed, interpreted and communicated. The study appeared to sweep aside all known benchmarks of scientific good practice and, more importantly, to ignore the minimal standards of scientific and ethical conduct in particular concerning the humane treatment of experimental animals.

Pick's disease is a subset of fronto-temporal dementia characterised by severe atrophy of the temporal and frontal lobes due to marked neuronal loss accompanied by astrocytic gliosis enriched in glial acidic protein. The remaining neurones have intracytoplasmic inclusions composed of hyperphosphorylated tau, called Pick bodies, in addition to hyperphosphorylated tau in astrocytes and oligodendrocytes. Gel electrophoresis and western blotting using markers of glycoxidation (advanced glycation end products, N-carboxyethyl-lysine and N-carboxymethyl-lysine: AGE, CEL, CML, respectively) and lipoxidation (4-hydroxy-2-nonenal: HNE, and malondialdehyde-lysine: MDAL) were used in the frontal and occipital cortex in three Pick's disease cases and three agematched controls. In Pick's disease, increased AGE, CML, CEL, HNE and MDAL bands of about 50 kDa were observed in the frontal cortex (but not in the occipital cortex) in association with increased density of glial acidic protein bands. Bi-dimensional gel electrophoresis and western blotting also disclosed increased amounts and numbers of glial acidic protein isoforms in the frontal cortex in Pick's disease. Moreover, redox proteomics showed glycoxidation, as revealed with anti-CEL antibodies and lipoxidation using anti-HNE antibodies, of at least three glial acidic protein isoforms. The present results demonstrate that glial acidic protein is a target of oxidative damage in the frontal cortex in Pick's disease.

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