Colloquium on scientific authorship: rights and responsibilities

The Colloquium on Scientific Authorship was held at the National Institutes of Health (NIH) at a time of extraordinary scrutiny by the public of the ethics of scientists, as represented by intense interest of the press and the Congress of the United States. Indeed, several regulations dealing with scientific misconduct have been proposed during the last year in the Federal Register, and new legislation has been proposed in the Congress. As a result of these concerns, conferences have been organized by the Institute of Medicine, the American Association for the Advancement of Science/American Bar Association, the Council of Biology Editors, and other groups. The colloquium at NIH, which was held May 31, 1988, and sponsored by the Intramural Scientists, focused on publication practices, especially multiple authorship, as contributing to perceived difficulties. The participants suggested various changes in conventions related to authorship that might help prevent future problems.     

Production of Hexagenia limbata nymphs in contaminated sediments in the Upper Great Lakes Connecting Channels

In April through October 1986, we sampled sediments and populations of nymphs of the burrowing mayfly, Hexagenia limbata (Serville), at 11 locations throughout the connecting channels of the upper Great Lakes, to determine if sediment contaminants adversely affected nymph production. Production over this period was high (980 to 9231 mg dry wt m^-2) at the five locations where measured sediment levels of oil, cyanide, and six metals were below the threshold criteria of the U.S. Environmental Protection Agency and the Ontario Ministry of Environment for contaminated or polluted sediments, and also where the criterion for visible oil given in the Water Quality Agreement between the U.S.A. and Canada for connecting waters of the Great Lakes was not exceeded. At the other six locations where sediments were polluted, production was markedly lower (359 to 872 mg dry wt m^-2). This finding is significant because it indicates that existing sediment quality criteria can be applied to protect H. limbata from oil, cyanide, and metals in the Great Lakes and connecting channels where the species fulfills a major role in secondary production and trophic transfer of energy.Contribution 733, of the National Fisheries Research Center-Great Lakes, U.S. Fish and Wildlife Service, 1451 Green Road, Ann Arbor, MI 48105.     

Sphingosine kinase expression regulates apoptosis and caspase activation in PC12 cells

Sphingosine-1-phosphate (SPP), a bioactive sphingolipid metabolite, suppresses apoptosis of many types of cells, including rat pheochromocytoma PC12 cells. Elucidating the molecular mechanism of action of SPP is complicated by many factors, including uptake and metabolism, as well as activation of specific G-protein-coupled SPP receptors, known as the endothelial differentiation gene-1 (EDG-1) family. In this study, we overexpressed type 1 sphingosine kinase (SPHK1), the enzyme that converts sphingosine to SPP, in order to examine more directly the role of intracellularly generated SPP in neuronal survival. Enforced expression of SPHK1 in PC12 cells resulted in significant increases in kinase activity, with corresponding increases in intracellular SPP levels and concomitant decreases in both sphingosine and ceramide, and marked suppression of apoptosis induced by trophic factor withdrawal or by C(2)-ceramide. NGF, which protects PC12 cells from serum withdrawal-induced apoptosis, also stimulated SPHK1 activity. Surprisingly, overexpression of SPHK1 had no effect on activation of two known NGF-stimulated survival pathways, extracellular signal regulated kinase ERK 1/2 and Akt. However, trophic withdrawal-induced activation of the stress activated protein kinase, c-Jun amino terminal kinase (SAPK/JNK), and activation of the executionary caspases 2, 3 and 7, were markedly suppressed. Moreover, this abrogation of caspase activation, which was prevented by the SPHK inhibitor N,N-dimethylsphingosine, was not affected by pertussis toxin treatment, indicating that the cytoprotective effect was likely not mediated by binding of SPP to cell surface G(i)-coupled SPP receptors. In agreement, there was no detectable release of SPP into the culture medium, even after substantially increasing cellular SPP levels by NGF or sphingosine treatment. In contrast to PC12 cells, C6 astroglioma cells secreted SPP, suggesting that SPP might be one of a multitude of known neurotrophic factors produced and secreted by glial cells. Collectively, our results indicate that SPHK/SPP may play an important role in neuronal survival by regulating activation of SAPKs and caspases.     

Salicylic acid-independent plant defence pathways

Salicylic acid is an important signalling molecule involved in both locally and systemically induced disease resistance responses. Recent advances in our understanding of plant defence signalling have revealed that plants employ a network of signal transduction pathways, some of which are independent of salicylic acid. Evidence is emerging that jasmonic acid and ethylene play key roles in these salicylic acid-independent pathways. Cross-talk between the salicylic acid-dependent and the salicylic acid-independent pathways provides great regulatory potential for activating multiple resistance mechanisms in varying combinations.     

Inhibition of neuronal apoptosis by docosahexaenoic acid (22:6n-3). Role of phosphatidylserine in antiapoptotic effect

Enrichment of Neuro 2A cells with docosahexaenoic acid (22:6n-3) decreased apoptotic cell death induced by serum starvation as evidenced by the reduced DNA fragmentation and caspase-3 activity. The protective effect of 22:6n-3 became evident only after at least 24 h of enrichment before serum starvation and was potentiated as a function of the enrichment period. During enrichment 22:6n-3 incorporated into phosphatidylserine (PS) steadily, resulting in a significant increase in the total PS content. Similar treatment with oleic acid (18:1n-9) neither altered PS content nor resulted in protective effect. Hindering PS accumulation by enriching cells in a serine-free medium diminished the protective effect of 22:6n-3. Membrane translocation of Raf-1 was significantly enhanced by 22:6n-3 enrichment in Neuro 2A cells. Consistently, in vitro biomolecular interaction between PS/phosphatidylethanolamine /phosphatidylcholine liposomes, and Raf-1 increased in a PS concentration-dependent manner. Collectively, enrichment of neuronal cells with 22:6n-3 increases the PS content and Raf-1 translocation, down-regulates caspase-3 activity, and prevents apoptotic cell death. Both the antiapoptotic effect of 22:6n-3 and Raf-1 translocation are sensitive to 22:6n-3 enrichment-induced PS accumulation, strongly suggesting that the protective effect of 22:6n-3 may be mediated at least in part through the promoted accumulation of PS in neuronal membranes.     

Androgen receptor status predicts response to chemotherapy, not risk of breast cancer in Indian women

Voltage gated potassium channels have been extensively studied in relation to cancer. In this review, we will focus on the role of two potassium channels, Ether à-go-go (Eag), Human ether à-go-go related gene (HERG), in cancer and their potential therapeutic utility in the treatment of cancer. Eag and HERG are expressed in cancers of various organs and have been implicated in cell cycle progression and proliferation of cancer cells. Inhibition of these channels has been shown to reduce proliferation both in vitro and vivo studies identifying potassium channel modulators as putative inhibitors of tumour progression. Eag channels in view of their restricted expression in normal tissue may emerge as novel tumour biomarkers.