Neverland is an evolutionally conserved Rieske-domain protein that is essential for ecdysone synthesis and insect growth

Steroid hormones mediate a wide variety of developmental and physiological events in multicellular organisms. During larval and pupal stages of insects, the principal steroid hormone is ecdysone, which is synthesized in the prothoracic gland (PG) and plays a central role in the control of development. Although many studies have revealed the biochemical features of ecdysone synthesis in the PG, many aspects of this pathway have remained unclear at the molecular level. We describe the neverland (nvd) gene, which encodes an oxygenase-like protein with a Rieske electron carrier domain, from the silkworm Bombyx mori and the fruitfly Drosophila melanogaster. nvd is expressed specifically in tissues that synthesize ecdysone, such as the PG. We also show that loss of nvd function in the PG causes arrest of both molting and growth during Drosophila development. Furthermore, the phenotype is rescued by application of 20-hydroxyecdysone or the precursor 7-dehydrocholesterol. Given that the nvd family is evolutionally conserved, these results suggest that Nvd is an essential regulator of cholesterol metabolism or trafficking in steroid synthesis across animal phyla.     

Effects on apoptosis and reactive oxygen species formation by Jurkat cells exposed to 50 Hz electromagnetic fields

The effect of exposure to 50 Hz electromagnetic field on a human T-leukaemia cell line (Jurkat) was investigated by evaluating the reactive oxygen species (ROS) production and apoptosis, both spontaneous and induced by a specific anti Fas/CD95 monoclonal antibody (anti-Fas). Our results suggest that 1 h intermittent (5 min field on/10 min field off) exposure does not affect ROS formation, while a slight but statistically significant decrease of both spontaneous and anti-Fas-induced apoptosis was observed.     

Isolation of cDNA clones corresponding to genes differentially expressed in pericarp of mume (Prunus mume) in response to ripening, ethylene and wounding signals

Ripening of climacteric fruit is a complex developmental process that includes many changes in gene expression. Some ripening-regulated genes are responsive to ethylene and/or wounding signals. Wounding increased Pm-ACS1 expression in Prunus mume (Japanese apricot), but was negatively regulated by ethylene. However, exposure of freshly harvested mature green mume fruit to ethylene induced PmACS1 . Fifteen complementary DNA clones corresponding to messenger RNAs differentially expressed in the pericarp of P. mume fruit in response to ripening, ethylene and wounding signals were isolated by differential display. Quantitative real-time PCR analysis distinctly showed that these genes are differentially regulated. Genes that were upregulated during fruit ripening include Pm15 (cinnamyl-alcohol dehydrogenase), Pm21 (2-oxoacid-dependent dioxygenase), Pm22 (1-acyl- sn -glycerol-3-phosphate acyltransferase), Pm27 (unknown function), Pm38 (alcohol dehydrogenase), Pm41 (no homology), Pm52 (no homology), Pm65 (pectate lyase), Pm68 (expansin), Pm69 (serine carboxypeptidase) and Pm94 (alcohol acyltransferase). Expression of most of these genes was also inducible by ethylene and some of them were inducible by wounding. Pm3 (water channel protein, MIP) and Pm8 (unknown function) were downregulated during ripening. Expression of Pm71 (no homology) and Pm74 (NAC family protein) did not increase during ripening or in response to ethylene, but was upregulated in response to wounding. The possible physiological roles of these genes during ripening and in response to ethylene and wounding are discussed.     

Redefining disease? The nosologic implications of molecular genetic knowledge

How will developments in genetic knowledge affect the classification of disease? Leaders in genetics have suggested that knowledge of the role of genes in disease can determine nosology. Diseases might be defined by genotype, thus avoiding the limitations of more empirical approaches to categorization. Other commentators caution against disease definitions that are detached from the look and feel of disease, and argue for an interplay between genotypic and phenotypic information. Still others attribute nosologic change to social processes. We draw on an analysis of the scientific literature, our conversations with genetics clinicians, and reviews of patient organization Web sites to offer a revised interpretation of the nosologic implications of molecular genetic knowledge. We review the recent histories of three diseases--hemophilia, Rett syndrome, and cystic fibrosis--to argue that nosologic change cannot be explained by either biologic theories of disease etiology or sociologic theories of social tendencies. Although new genetic information challenges disease classifications and is highly influential in their redesign, genetic information can be used in diverse ways to reconstruct disease categories and is not the only influence in these revisions. Ironically, genetic information is likely to play a central role in producing a new, but still empirical, classification scheme.     

Cloning and expression of two crystal protein genes, cry30Ba1 and cry44Aa1, obtained from a highly mosquitocidal strain, Bacillus thuringiensis subsp. entomocidus INA288

Two novel crystal protein genes, cry30Ba and cry44Aa, were cloned from Bacillus thuringiensis subsp. entomocidus INA288 and expressed in an acrystalliferous strain. Cry44Aa crystals were highly toxic to second-instar Culex pipiens pallens (50% mortality concentration [LC50] = 6 ng/ml) and Aedes aegypti (LC50 = 12 ng/ml); however, Cry30Ba crystals were not toxic.     

Tryptamine-gallic acid hybrid prevents non-steroidal anti-inflammatory drug-induced gastropathy: correction of mitochondrial dysfunction and inhibition of apoptosis in gastric mucosal cells

We have investigated the gastroprotective effect of SEGA (3a), a newly synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a) prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing gastropathy. SEGA (3a) offers this mitoprotective effect by scavenging of mitochondrial superoxide anion (O(2)(·-)) and intramitochondrial free iron released as a result of MOS. SEGA (3a) in vivo blocks indomethacin-mediated MOS, as is evident from the inhibition of indomethacin-induced mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. SEGA (3a) corrects indomethacin-mediated mitochondrial dysfunction in vivo by restoring defective electron transport chain function, collapse of transmembrane potential, and loss of dehydrogenase activity. SEGA (3a) not only corrects mitochondrial dysfunction but also inhibits the activation of the mitochondrial pathway of apoptosis by indomethacin. SEGA (3a) inhibits indomethacin-induced down-regulation of bcl-2 and up-regulation of bax genes in gastric mucosa. SEGA (3a) also inhibits indometacin-induced activation of caspase-9 and caspase-3 in gastric mucosa. Besides the gastroprotective effect against NSAID, SEGA (3a) also expedites the healing of already damaged gastric mucosa. Radiolabeled ((99m)Tc-labeled SEGA (3a)) tracer studies confirm that SEGA (3a) enters into mitochondria of gastric mucosal cell in vivo, and it is quite stable in serum. Thus, SEGA (3a) bears an immense potential to be a novel gastroprotective agent against NSAID-induced gastropathy.