Upon binding of cortisol, the glucocorticoid receptor (GR) regulates the transcription of specific target genes, including those that encode the stress hormones corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH). Dysregulation of the stress axis is a hallmark of major depression in human patients. However, it is still unclear how glucocorticoid signaling is linked to affective disorders. We identified an adult-viable zebrafish mutant in which the negative feedback on the stress response is disrupted, due to abolition of all transcriptional activity of GR. As a consequence, cortisol is elevated, but unable to signal through GR. When placed into an unfamiliar aquarium (‘novel tank’), mutant fish become immobile (‘freeze’), show reduced exploratory behavior and do not habituate to this stressor upon repeated exposure. Addition of the antidepressant fluoxetine to the holding water and social interactions restore normal behavior, followed by a delayed correction of cortisol levels. Fluoxetine does not affect overall transcription of CRH, the mineralocorticoid receptor (MR), the serotonin transporter Serta or GR itself. Fluoxetine, however, suppresses the stress-induced upregulation of MR and Serta in both wildtype fish and mutants. Our studies show a conserved, protective function of glucocorticoid signaling in the regulation of emotional behavior and reveal novel molecular aspects of how chronic stress impacts vertebrate brain physiology and behavior. Importantly, the zebrafish model opens up the possibility of high-throughput drug screens in search of new classes of antidepressants.

The gas-phase valence binding energy spectrum of isolated ion-pairs of the commonly used [1-ethyl-3-methylimidazolium][bis(trifluoromethylsulfonyl)imide)] room-temperature ionic liquid is obtained by photoionization of a molecular beam of ionic liquid vapor by extreme ultraviolet light. The isolated ion-pair nature of the ionic liquid vapor is corroborated by single photon ionization mass spectroscopy, complemented by computed vaporization energetics of ion-pairs and clusters of ion-pairs. The valence binding energy spectrum of the isolated ion-pairs is discussed in comparison with available liquid-phase data and theoretical density functional theory calculations.

A multifaceted agreement between ab initio theoretical predictions and experimental measurements, including branching ratios, channel-specic kinetic energy release, and three-body momentum correlation spectra, leads to the identication of new mechanisms in Coulomb-explosion (CE) induced two-and three-body breakup processes in