The advent of a novel diagnosis: melanoma through the ages.

In the 1930s, the risk of contracting melanoma was only 1:1500; however, by 1996 this number had risen to 1:87 and has been increasing ever since. To better understand the nature of melanoma, books, journals, and scholarly literary works were searched and contributors of this disease were studied in greater detail. Antiquity of melanoma is said to be approximately 2400 years old based on observations made on 9 Peruvian Inca mummies in the 1960s that showed apparent signs of melanoma. René Théophile Hyacinthe Laënnec, the inventor of the stethoscope, first described melanoma as a disease entity. William Norris, an English general practitioner, gave the first English language report of this disease. There are many other physicians from France, England, and the United States who had an active role in the discovery of melanoma.

Expression of zinc-deficient human superoxide dismutase in Drosophila neurons produces a locomotor defect linked to mitochondrial dysfunction.

More than 130 different mutations in the Cu/Zn superoxide dismutase (SOD1) gene have been associated with amyotrophic lateral sclerosis but the mechanism of this toxicity remains controversial. To gain insight into the importance of the zinc site in the pathogenesis of SOD1 in vivo, we generated a Drosophila model with transgenic expression of a zinc-deficient human SOD1. Expression of zinc-deficient SOD1 in Drosophila resulted in a progressive movement defect with associated mitochondrial cristae vacuolization and reductions in adenosine triphosphate (ATP) levels. Furthermore, these flies are sensitized to mitochondrial toxins, paraquat, and zinc. Importantly, we show that the zinc-deficient SOD1-induced motor defect can be ameliorated by supplementing the endogenous fly respiratory chain machinery with the single-subunit NADH-ubiquinone oxidoreductase from yeast (NADH is nicotinamide adenine dinucleotide, reduced form.). These results demonstrate that zinc-deficient SOD1 is neurotoxic in vivo and suggest that mitochondrial dysfunction plays a critical role in this toxicity. The robust behavioral, pathological, and biochemical phenotypes conferred by zinc-deficient SOD1 in Drosophila have general implications for the role of the zinc ion in familial and sporadic amyotrophic lateral sclerosis.

Extension of Drosophila life span by RNAi of the mitochondrial respiratory chain.

BACKGROUND: Mitochondria have long been proposed to play an important role in the aging process. In the nematode Caenorhabditis elegans, genes important for mitochondrial electron transport chain (ETC) function stand out as a principal group of genes affecting life span. However, it has been suggested that this may be a peculiarity of nematode biology. In the present study, we have used an in vivo RNA interference (RNAi) strategy to inactivate ETC genes in Drosophila melanogaster and examine the impact on longevity. RESULTS: Here, we report that RNAi of five genes encoding components of mitochondrial respiratory complexes I, III, IV, and V leads to increased life span in flies. Long-lived flies with reduced expression of ETC genes do not consistently show reduced assembly of respiratory complexes or reduced ATP levels. In addition, extended longevity is not consistently correlated with reduced fertility or increased resistance to the free-radical generator paraquat. Targeted RNAi of two complex I genes in adult tissues or in neurons alone is sufficient to extend life span. CONCLUSIONS: Our data suggest that the role of mitochondrial ETC function in modulating animal aging is evolutionarily conserved and might also operate in humans. Furthermore, our findings suggest that the longer life span of flies with reduced ETC gene expression cannot simply be attributed to reduced energy production leading to decreased "rate of living."