Endothelin-1 promotes phosphorylation of CREB transcription factor in primary cultures of neonatal rat cardiac myocytes: implications for the regulation of c-jun expression.

Cardiac myocyte hypertrophy is associated with an increase in expression of immediate early genes (e.g. c-jun) via activation of pre-existing transcription factors. The activity of CREB transcription factor is regulated through phosphorylation of Ser-133 by one of several protein kinases (e.g. protein kinase A (PKA), p90 ribosomal S6 kinases (RSKs) and the related kinase, MSK1). A cell-permeable form of cAMP, hypertrophic agonists (endothelin-1 (ET-1), phenylephrine (PE)) and hyperosmotic shock all promoted phosphorylation of CREB(Ser-133) in rat neonatal cardiac myocytes. The response to endothelin-1 required the extracellular signal-regulated kinase cascade which stimulates both RSKs and MSK1. Phosphorylation of CREB(Ser-133) in response to ET-1 was not associated with any increase in DNA binding to a consensus cAMP-response element (CRE). The rat c-jun promoter contains elements which may bind either c-Jun/ATF2 or CREB/ATF1 dimers. Using extracts from rat cardiac myocytes, we identified at least two complexes which bind to the most proximal of these elements, one of which contained CREB and the other c-Jun. Thus, phosphorylation and activation of CREB in cardiac myocytes may be effected by a range of different stimuli to influence the expression of immediate early genes such as c-jun.

The effects of acute fluoxetine administration on temporal discounting in youth with ADHD

Background Serotonin is under-researched in attention deficit hyperactivity disorder (ADHD), despite accumulating evidence for its involvement in impulsiveness and the disorder. Serotonin further modulates temporal discounting (TD), which is typically abnormal in ADHD relative to healthy subjects, underpinned by reduced fronto-striato-limbic activation. This study tested whether a single acute dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine up-regulates and normalizes reduced fronto-striato-limbic neurofunctional activation in ADHD during TD. Method Twelve boys with ADHD were scanned twice in a placebo-controlled randomized design under either fluoxetine (between 8 and 15 mg, titrated to weight) or placebo while performing an individually adjusted functional magnetic resonance imaging TD task. Twenty healthy controls were scanned once. Brain activation was compared in patients under either drug condition and compared to controls to test for normalization effects. Results Repeated-measures whole-brain analysis in patients revealed significant up-regulation with fluoxetine in a large cluster comprising right inferior frontal cortex, insula, premotor cortex and basal ganglia, which further correlated trend-wise with TD performance, which was impaired relative to controls under placebo, but normalized under fluoxetine. Fluoxetine further down-regulated default mode areas of posterior cingulate and precuneus. Comparisons between controls and patients under either drug condition revealed normalization with fluoxetine in right premotor-insular-parietal activation, which was reduced in patients under placebo. Conclusions The findings show that a serotonin agonist up-regulates activation in typical ADHD dysfunctional areas in right inferior frontal cortex, insula and striatum as well as down-regulating default mode network regions in the context of impulsivity and TD.

White youth: the Far Right, Punk and British youth culture

‘White Youth’ recovers and explains the relationship between far-right organisations and British youth culture in the period between 1977 and 1987. In particular, it concentrates on the cultural spaces opened up by punk and the attempts made by the National Front and British Movement to claim them as conduits for racist and/or ultra-nationalist politics. The article is built on an empirical basis, using archival material and a historical methodology chosen to develop a history ‘from below’ that takes due consideration of the socio-economic and political forces that inform its wider context. Its focus is designed to map shifting cultural and political influences across the far right, assessing the extent to which extremist organisations proved able to adopt or utilise youth cultural practice as a means of recruitment and communication. Today the British far right is in political and organisational disarray. Nonetheless, residues tied to the cultural initiatives devised in the 1970s–80s remain, be they stylistic, nostalgic or points of connection forged to connect a transnational music scene.

Mediated addiction: The drug discourses of Hong Kong youth

This paper examines the ways young people in Hong Kong at different stages of involvement with illegal drugs respond to government produced anti-drug television commercials through a methodology which provided them with the technical skills and equipment to make their own short videos about drugs. An analysis of the videos they produced and their interaction while producing them reveals that participants with different drug-taking experiences have very different and often multiple ways of talking about drugs, and that these different ‘discourses’ and the ways they are deployed in different contexts affect how ‘at-risk’ they are for new or continued drug use and how they respond to anti-drug messages designed to mitigate this risk.