RNASeq analysis of differentiated keratinocytes reveals a massive response to late events during human papillomavirus type 16 infection, including loss of epithelial barrier function.

The human papillomavirus (HPV) replication cycle is tightly linked to epithelial cell differentiation. To examine HPV-associated changes in the keratinocyte transcriptome, RNAs isolated from undifferentiated and differentiated cell populations of normal, spontaneously immortalised, keratinocytes (NIKS), and NIKS stably transfected with HPV16 episomal genomes (NIKS16), were compared using RNASeq. HPV16 infection altered expression of 2862 cellular genes. Next, to elucidate the role of keratinocyte gene expression in late events during the viral life cycle, RNASeq was carried out on triplicate differentiated populations of NIKS (uninfected) and NIKS16 (infected). Of the top 966 genes altered (>log2 = 1.8, 3.5-fold change) 670 genes were downregulated and 296 genes were up-regulated. HPV down-regulated many genes involved in epithelial barrier function that involves structural resistance to the environment and immunity to infectious agents. For example, HPV infection repressed expression of the differentiated keratinocyte-specific pattern recognition receptor TLR7, the Langerhans cell chemoattractant, CCL20, and proinflammatory cytokines, IL1A and IL1B. However, IRF1, IFNκ and viral restriction factors (IFIT1, 2, 3, 5, OASL, CD74, RTP4) were up-regulated. HPV infection abrogated gene expression associated with the physical epithelial barrier, including keratinocyte cytoskeleton, intercellular junctions and cell adhesion. qPCR and western blotting confirmed changes in expression of seven of the most significantly altered mRNAs. Expression of three genes showed statistically significant changes during cervical disease progression in clinical samples. Taken together, the data indicate that HPV infection manipulates the differentiating keratinocyte transcriptome to create an environment conducive to productive viral replication and egress.IMPORTANCE Human papillomavirus (HPV) genome amplification and capsid formation takes place in differentiated keratinocytes. The viral life cycle is intimately associated with host cell differentiation. Deep sequencing (RNASeq) of RNA from undifferentiated and differentiated uninfected and HPV16-positive keratinocytes showed that almost 3000 genes were differentially expressed in keratinocyte due to HPV16 infection. Strikingly, the epithelial barrier function of differentiated keratinocytes, comprising keratinocyte immune function and cellular structure, was found to be disrupted. These data provide new insights into virus-host interaction crucial for production of infectious virus and reveal that HPV infection remodels keratinocytes for completion of the virus replication cycle

A typology of convergences: a theory of cultural transmission

Adelaide Festival of Ideas session, Chandelier Room West, Freemasons Hall, 1:30pm, Sunday 20th October, 2013. Hosted by Nici Cumpston.Lawrence Weschler is exploring how we see the world and untangling the ways we engage with our visual culture. In this talk, Weschler will consider a spectrum of convergent effects, from the tendency of humans to see patterns where none exist, to the impact of influence homage, allusion, quotation and appropriation, through to outright plagiarism.Lawrence Weschlerhttp://adelaidefestivalofideas.com.au

A twist in time

Adelaide Festival of Ideas session, Freemasons Chandelier Room, 10:00 am, Saturday 19th October, 2013. Chaired by Erica Green.One of the main threads of Daniel Crook’s striking moving image artworks at the Samstag Museum is the treatment of time as a spatial dimension, as a tangible and malleable material. Crooks meets with Lawrence Weschler, author of the exhibition’s catalogue essay, to discuss how he has become one of Australia’s most intriguing and successful visual artists.Presented by the Anne and Gordon Samstag Museum of Art in collaboration with AFF The Adelaide Festival of Ideas is recorded by Radio Adelaide through the support of The Barr Smith Library, University of Adelaide, University of South Australia Library and Flinders University Library.http://adelaidefestivalofideas.com.a

Slave to the Rhythm: The Problem of Creative Pedagogy and the Teaching of Creativity

Since the mid-twentieth century the concepts ‘creativity’ and ‘innovation’ have become increasingly significant within a host of fields, such as education, medicine, engineering, technology and science. Moreover, such terms appear to have become ubiquitous, if not hegemonic, within the contemporary discourses that inform debates that surround the allocation and cultivation of the social capital that is native to education, both tertiary and otherwise. Given that the thinking of creativity appears increasingly to be possible only within the contemporary logics of utility and productivity that inform the discussion of the ‘knowledge economy’, the philosophical works of Gilles Deleuze are perhaps now more vital than ever, at least insofar as he is able to provide the possibility of approaching an ‘otherwise’ to the contemporary thinking of ‘creativity’. This paper discusses the possibility for Deleuze’s discussion of rhythm – as can be located in his text A Thousand Plateaus and his work on the twentieth-century painter Francis Bacon – as providing the means for better posing the question of the conditions for the emergence of a fundamentally creative approach to teaching creativity to be conceptualized within our present situation