The bile acid receptor TGR5 does not interact with β-arrestins or traffic to endosomes but transmits sustained signals from plasma membrane rafts.

TGR5 is a G protein-coupled receptor that mediates bile acid (BA) effects on energy balance, inflammation, digestion and sensation. The mechanisms and spatiotemporal control of TGR5 signaling are poorly understood. We investigated TGR5 signaling and trafficking in transfected HEK293 cells and colonocytes (NCM460) that endogenously express TGR5. BAs (deoxycholic acid, DCA, taurolithocholic acid, TLCA) and the selective agonists oleanolic acid (OA) and 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N, 5-dimethylisoxazole-4-carboxamide (CCDC) stimulated cAMP formation but did not induce TGR5 endocytosis or recruitment of β-arrestins, assessed by confocal microscopy. DCA, TLCA and OA did not stimulate TGR5 association with β-arrestin 1/2 or G protein-coupled receptor kinase (GRK) 2/5/6, determined by bioluminescence resonance energy transfer. CCDC stimulated a low level of TGR5 interaction with β-arrestin2 and GRK2. DCA induced cAMP formation at the plasma membrane and cytosol, determined using exchange factor directly regulated by cAMP (Epac2)-based reporters, but cAMP signals did not desensitize. AG1478, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, the metalloprotease inhibitor batimastat, and methyl-β-cyclodextrin and filipin, which block lipid raft formation, prevented DCA stimulation of extracellular signal regulated kinase (ERK1/2). BRET analysis revealed TGR5 and EGFR interactions that were blocked by disruption of lipid rafts. DCA stimulated TGR5 redistribution to plasma membrane microdomains, localized by immunogold electron microscopy. Thus, TGR5 does not interact with β-arrestins, desensitize or traffic to endosomes. TGR5 signals from plasma membrane rafts that facilitate EGFR interaction and transactivation. An understanding of the spatiotemporal control of TGR5 signaling provides insights into the actions of BAs and therapeutic TGR5 agonists/antagonists.

Voice, body and the transmission of the real in documentary theatre

This article analyses how listening is used to develop performances in Alecky Blythe’s verbatim theatre. Listening includes Blythe’s use of recorded oral interviews for devising performances, and also the actors’ creation of performance by precisely imitating an interviewee’s voice. The article focuses on listening, speaking and embodiment in London Road, Blythe’s recent musical play at London’s National Theatre, which adopted and modified theatre strategies used in her other plays, especially The Girlfriend Experience and Do We look Like Refugees. The article draws on interviews with performers and with Blythe herself, in its critical analysis of how voice legitimates claims to authenticity in performance. The work on Blythe is contextualised by brief comparative analyses. One is Clio Barnard’s film The Arbor, a ‘quasi-documentary’ on the playwright, Andrea Dunbar which makes use of an oral script to which the actors lip-sync. The other comparator is the Wooster Group’s Poor Theater, which attempts to recreate Grotowski's Akropolis via vocal impersonation. The article argues that voice in London Road both claims and defers authenticity and authority, inasmuch as voice signifies presence and embodied identity but the reworking of speech into song signals the absence of the real. The translation of voice into written surtitles works similarly in Do We Look Like Refugees. Blythe’s theatre, Barnard’s film and The Wooster Group’s performances are a useful framework for addressing questions of voice and identity, and authenticity and replication in documentary theatre. The article concludes by placing Blythe’s oral texts amid current debates around theatre’s textual practices.

Computing journey start times with recurrent traffic conditions

n this study, the authors discuss the effective usage of technology to solve the problem of deciding on journey start times for recurrent traffic conditions. The developed algorithm guides the vehicles to travel on more reliable routes that are not easily prone to congestion or travel delays, ensures that the start time is as late as possible to avoid the traveller waiting too long at their destination and attempts to minimise the travel time. Experiments show that in order to be more certain of reaching their destination on time, a traveller has to leave early and correspondingly arrive early, resulting in a large waiting time. The application developed here asks the user to set this certainty factor as per the task in hand, and computes the best start time and route.

Finding the 'first voice' in rural England: the challenges of safeguarding intangible heritage in a national museum

This paper is an attempt to explore the challenges of defining intangible heritage and ‘community’ in England. It uses as its case study the Museum of English Rural Life, University of Reading: an urban museum with a rural theme. The paper examines current theoretical discourse around the concept of the ‘first voice’ and debate about the role of museums in the preservation of intangible heritage. It then examines the relevance of these concepts to the identification of ‘rural’ intangible heritage stake holders in England. In this way, it shows the potential for concepts of intangible heritage to influence national museums. However, by applying theory and practice which is designed to support work with well-defined ‘originating communities’ to a national museum, it also highlights the challenges of initiating community engagement in a multicultural society.

Institutions, unionization and voice: the relative impact of context and actors on firm level practice

Trade unions provide a voice in the way firms are run, an input into reward systems and increased security of employment. But these vary with national context. Using transnational survey evidence, this article explores the relative impact of setting, and of unions and collective bargaining, on these issues. It is found that, irrespective of context, organizations are significantly more likely to make use of compulsory redundancies in the absence of unions and collective bargaining. However, in other areas, the impact of unions appeared less pronounced than that of the wider context. The article explores the reasons behind this, and the broader policy implications thereof.

Atypical processing of voice sounds in infants at risk for Autism Spectrum Disorder

Adults diagnosed with autism spectrum disorder (ASD) show a reduced sensitivity (degree of selective response) to social stimuli such as human voices. In order to determine whether this reduced sensitivity is a consequence of years of poor social interaction and communication or is present prior to significant experience, we used functional MRI to examine cortical sensitivity to auditory stimuli in infants at high familial risk for later emerging ASD (HR group, N = 15), and compared this to infants with no family history of ASD (LR group, N = 18). The infants (aged between 4 and 7 months) were presented with voice and environmental sounds while asleep in the scanner and their behaviour was also examined in the context of observed parent-infant interaction. Whereas LR infants showed early specialisation for human voice processing in right temporal and medial frontal regions, the HR infants did not. Similarly, LR infants showed stronger sensitivity than HR infants to sad vocalisations in the right fusiform gyrus and left hippocampus. Also, in the HR group only, there was an association between each infant's degree of engagement during social interaction and the degree of voice sensitivity in key cortical regions. These results suggest that at least some infants at high-risk for ASD have atypical neural responses to human voice with and without emotional valence. Further exploration of the relationship between behaviour during social interaction and voice processing may help better understand the mechanisms that lead to different outcomes in at risk populations.

The application of social marketing in reducing road traffic accidents amoung young male drivers: an investigation using physical fear threat appeals

There were 338 road fatalities on Irish roads in 2007. Research in 2007 by the Road Safety Authority in Ireland states that young male drivers (17 – 25 years) are seven times more likely to be killed on Irish roads than other road users. The car driver fatality rate was found to be approximately 10 times higher for young male drivers than for female drivers in 2000. Young male drivers in particular demonstrate a high proclivity for risky driving behaviours. These risky behaviours include drink driving, speeding, rug-driving and engaging in aggressive driving. Speed is the single largest contributing factor to road deaths in Ireland. Approximately 40% of fatal accidents are caused by excessive or inappropriate speed. This study focuses on how dangerous driving behaviours may be addressed through social marketing. This study analyses the appropriate level of fear that needs to be induced in order to change young male driving behaviour.

Litigation against fracking bans and moratoriums in the US: exit, voice and loyalty

A number of US states, counties and municipalities have responded to the public health and environmental concerns surrounding fracking by imposing bans or moratoriums on unconventional oil and gas drilling. These restrictions have, in recent years, given rise to litigation challenges by oil and gas companies and by property owners deprived of potential revenues. The current article begins by examining precisely who has litigated. Have large companies dominated or is it mostly smaller independents? Is there a difference in litigation rates between private and public companies? The article then considers how Hirschman’s ideas of exit, voice and loyalty might apply in the context of bans and moratoriums and further explores some of the factors that may have driven litigation in the area.

Voice, appropriation and discourse representation in a student writing task

We investigate the practices by which bilingual university students in Hong Kong appropriate texts in producing utterances, particularly written texts. Following Wertsch and his colleagues we ask: • To what extent do our students appropriate texts in constructing their own discourses? • What linguistic means do they use to do this? • What can these processes tell us about what they now can do with discourse representation; and • What do we need to teach them? This research shows that our students' writing displays considerable intertextuality and interdiscursivity. Responses to this writing in tutorial sessions indicate that they are skilled at orchestrating the multiple voices within their own discourses. The commonly stated concern that our students do not know how to do quotation and citation correctly is somewhat misplaced and researchers need to move the focus away from the mechanisms of citation and attribution to the social practices of textual appropriation.

Teaching pronunciation through voice quality

This paper explores the role of voice quality in the teaching of pronunciation and argues that since voice quality encompasses so many aspects of phonology, it provides a useful point of departure for pronunciation work. A teaching technique is described, in which the concept of voice quality is used in communicative practice to give students the opportunity to identify meaningful aspects of suprasegmental pronunciation, and see how they fit into the overall pattern of connected speech.