Interactions between serotonergic genotype and amino acid transmitter receptor expression in human alcoholics

Serotonin can modulate the activity of neural reward pathways that are strongly implicated in mediating the effects of chronic alcohol misuse, and its treatment, in human subjects. In previous work and as discussed elsewhere at this meeting, we and others have found consistent differences in the parameters of GABA and glutamate receptors, and the expression of their component subunit transcripts and proteins, in areas of the alcoholic brain that are altered by alcoholism. We did not fi nd clear changes in GABA and glutamate transport function in such samples, but a series of microarray analyses showed consistent upregulation of the presynaptic GABA/betaine transporter SLC6A12. Microarray studies showed no signifi cant differences in the expression of transcripts associated with 5HT transmission; however, only a small number of such elements were present on the arrays. Here we partitioned GABAA and NMDA pharmacology, and subunit mRNA and protein expression, measured in samples of frontal and motor cortex obtained at autopsy from alcoholics without comorbid disease, alcoholics with liver cirrhosis, and controls, according to 5HTTLPR (SLC6A4) and 5HT1B (HTR1B) polymorphisms. We found no effect of these genotypes on the expression of GABAA receptor gene products, but there was a signifi cant mRNA Transcript X Area X Group X 5HTTLPR Interaction with NMDA subunit isoform expression measured by Real Time PCR with GAPDH normalization. Further analysis showed the effect to be selective for alcoholics with cirrhosis, to be most marked in the pathologically vulnerable frontal cortex, and to vary with subunit transcript (F2,76 = 6.545, P = 0.002). NR1 expression was most affected, followed by NR2A, with NR2B expression least altered. Pilot data suggest 5HT1B genotype may also modulate NMDA subunit expression. Interactions between amino acid and serotonin transmission may infl uence susceptibility to alcohol dependence or pathogenesis

A participatory design agenda for ubiquitous computing and multimodal interaction: A case study of dental practice

This paper reflects upon our attempts to bring a participatory design approach to design research into interfaces that better support dental practice. The project brought together design researchers, general and specialist dental practitioners, the CEO of a dental software company and, to a limited extent, dental patients. We explored the potential for deployment of speech and gesture technologies in the challenging and authentic context of dental practices. The paper describes the various motivations behind the project, the negotiation of access and the development of the participant relationships as seen from the researchers' perspectives. Conducting participatory design sessions with busy professionals demands preparation, improvisation, and clarity of purpose. The paper describes how we identified what went well and when to shift tactics. The contribution of the paper is in its description of what we learned in bringing participatory design principles to a project that spanned technical research interests, commercial objectives and placing demands upon the time of skilled professionals. Copyright © 2010 ACM, Inc