Hypoxia is a common cause of cell death and is implicated in many disease processes including stroke and chronic degenerative disorders. In response to hypoxia, cells express a variety of genes, which allow adaptation to altered metabolic demands, decreased oxygen demands, and the removal of irreversibly damaged cells. Using polymerase chain reaction-based suppression subtractive hybridization to find genes that are differentially expressed in hypoxia, we identified the BH3-only Bcl-2 family protein Noxa. Noxa is a candidate molecule mediating p53-induced apoptosis. We show that Noxa promoter responds directly to hypoxia via hypoxia-inducible factor (HIF)-1 ␣ . Suppression of Noxa expression by antisense oligonucleotides rescued cells from hypoxia-induced cell death and decreased infarction volumes in an animal model of ischemia. Further, we show that reactive oxygen species and resultant cytochrome c release participate in Noxa-mediated hypoxic cell death. Altogether, our results show that Noxa is induced by HIF-1 ␣ and mediates hypoxic cell death.

h i g h l i g h t s • The first global review of anguillid population data and conservation status. • Eel population data currently fall short of required length and geographic range. • Multiple, synergistic, yet variable threats face eels across all life-history stages.• Key recommendations made for input into international eel conservation strategies. a b s t r a c tWith broad distributions, diadromous fishes can be exposed to multiple threats at different stages of development. For the primarily catadromous eels of the family Anguillidae, there is growing international concern for the population abundance and escapement trends of some of these species and yet incomplete knowledge of their remarkable life-histories hampers management and conservation. Anguillids experience a suite of pressures that include habitat loss/modification, migration barriers, pollution, parasitism, exploitation, and

Cytokines regulate lymphocyte development and differentiation, but precisely how they control these processes is still poorly understood. By using microarray technology to detect cytokineinduced genes, we identified a cDNA encoding Cybr, which was