Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

The Uses of Stance in Media Production: Embodied Sociolinguistics and Beyond

While many conversation analysts, and scholars in related fields, have used video-recordings to study interaction, this study is one of a small but growing number that investigates video-recordings of the joint activities of media professionals working with, and on, video. It examines practices of media production that are, in their involvement with the visual and verbal qualities of video, both beyond talk and deeply shaped by talk. The article draws upon video recordings of the making of a feature-length documentary. In particular, it analyses a complex course of action where an editing team are reviewing their interview of the subject of the documentary, their footage is being intercut with existing reality TV footage of that same interviewee. The central contributions that the article makes are, firstly, to the sociolinguistics of mediatisation, through the identification of the workplace concerns of the members of the editing team, secondly showing how editing is accomplished, moment-by-moment, through the use of particular forms of embodied action and, finally, how the media themselves feature in the ordering of action. While this is professional work it sheds light on the video-mediated practices in contemporary culture, especially those found in social media where video makers carefully consider their editing of the perspective toward themselves and others

Conversation analysis and the study of sociohistorical change

We reflect on the affordances and challenges of interactional data in the analysis of long-term institutional change. To this end we draw on our studies of direct encounters between journalists and politicians in news interviews and presidential news conferences and in particular the use of question design as a window into the evolution of journalistic norms and press-state relations over time and the causal antecedents of such change. All analyses that incorporate a concern with environing contexts of interactional change impose certain burdens of empirical demonstration on the researcher. Here we consider three analytic issues that arise in the kind of historical-institutional analysis we have been pursuing: (a) controlling for the situational context, (b) pinpointing the locus of change, and (c) validating indicators of change. Data are in English