Impediments to Cosmopolitan Engagement: Technology and Late-Modern Cosmopolitanism

What characterises late modern variety of cosmopolitanism from its classical predecessors is the inherent connection between cosmopolitanism and technology. Technology enables a vital dimension of the cosmopolitan experience – to move beyond the cosmopolitan imagination to enable active, direct engagement with other cultures. Different types of technologies contribute to cosmopolitan practice but in this paper we focus on a specific set of these enabling technologies: technologies which play a crucial role in regulating the free movement of people and populations. We briefly examine how three of the great surveillance states of the 20th century – Nazi Germany, the Soviet Union, and the German Democratic Republic – used hightech solutions in pursuing an anti-cosmopolitanism. We suggest that in the period from 2001 to the present, important elements of the cosmopolitan ethos are being closed down, and once again high-tech is intimately connected to this moment. The increasing (and proposed) use of identity cards, biometric identification systems, ITS and GIS all work to make the globalised world much harder to traverse and inhibit the full expression and experience of cosmopolitanism. The result of these trends may be that the type of cosmopolitan sentiment exhibited in western countries is an ersatz, emptied out variety with little political-ethical robustness.

(Dia)logics of difference : disability, performance & spectatorship

In this paper I examine the way artists with disabilities use performances in public spaces to encourage people to reflect on their own contribution to the construction of publics, or counter-publics, during and after the moment of encounter. I focus on Liz Crow’s Resistance on the Plinth. This is the title Crow gave her performance on the Forth Plinth in Trafalgar Square as part of Antony Gormley’s One and Other project in 2009. Described as a public art project presenting a portrait of the U.K., Gormley’s One and Other gave 2400 people selected at random via a lottery the chance to do whatever they chose for an hour on the vacant Forth Plinth in Trafalgar Square. In her hour, Crow chose to present herself in a Nazi uniform, in her wheelchair. In this paper, I discuss how Crow’s performance used a counterposition of images – the Nazi uniform, associated with eugenics and a desire to eliminate people who do not accord with the Arayan ‘norm’, counterposed with her wheelchair – to encourage passersby to “stop, look, think.” I examine how Crow used this counterposition to prevent passersby from attributing a single, stable, monologic meaning to the image – forestalling the risk that passersby would read the image as a Nazi on the Plinth – and instead draw passersby into a dialogue in which the impossibility of reconciling the contradictory images, ideologies and cultural logics Crow embodied encouraged people to continue thinking and talking about these cultural logics during and after the encounter.

(Dia)logics of difference disability, performance and spectatorship in Liz Crow's Resistance on the Plinth

In this article I examine how artists with disabilities use public-space performance to encourage passersby to reflect on the construction of public discourses about disability – and, therefore, the construction of publics that are potentially inclusive of people with disabilities. I concentrate on British storyteller, artist, filmmaker and activist Liz Crow's Resistance on the Plinth, one of four pieces Crow has produced over the past three years as part of the Resistance series, an examination of the Nazi regime's Aktion T4 programme, which resulted in the mass murder of a quarter of a million people with disabilities. Created in August 2009 as part of Antony Gormley's One & Other public art project, the piece featured Crow dressed in a Nazi uniform and seated in a wheelchair on the Fourth Plinth in London's Trafalgar Square. For Crow – who creates work in a British context where public debate about the eugenics of genetic testing, euthanasia and assisted suicide is prevalent in the media – the Nazi atrocity is still rich in confronting imagery, resonant and relevant in a contemporary context. In this article, I consider the challenges that Gormley's extremely public One & Other presented for professional artists like Crow, who are committed to intervening in public perceptions of identity, community and culture. I describe the structural choices Crow made to provoke debate about the cultural logics embodied in the image she presented, and analyse some of the spectatorial responses from online forums such as the One & Other website, Facebook and Twitter immediately following the event.

VAMP3 regulates podosome organisation in macrophages and together with Stx4/SNAP23 mediates adhesion, cell spreading and persistent migration

The ability of cells to adhere, spread and migrate is essential to many physiological processes, particularly in the immune system where cells must traffic to sites of inflammation and injury. By altering the levels of individual components of the VAMP3/Stx4/SNAP23 complex we show here that this SNARE complex regulates efficient macrophage adhesion, spreading and migration on fibronectin. During cell spreading this complex mediates the polarised exocytosis of VAMP3- positive recycling endosome membrane into areas of membrane expansion, where VAMP3's surface partner Q-SNARE complex Stx4/SNAP23 was found to accumulate. Lowering the levels of VAMP3 in spreading cells resulted in a more rounded cell morphology and most cells were found to be devoid of the typical ring-like podosome superstructures seen normally in spreading cells. In migrating cells lowering VAMP3 levels disrupted the polarised localisation of podosome clusters. The reduced trafficking of recycling endosome membrane to sites of cell spreading and the disorganised podosome localisation in migrating macrophages greatly reduced their ability to persistently migrate on fibronectin. Thus, this important SNARE complex facilitates macrophage adhesion, spreading, and persistent macrophage migration on fibronectin through the delivery of VAMP3-positive membrane with its cargo to expand the plasma membrane and to participate in organising adhesive podosome structures.

Syntaxin 11 binds Vti1b and regulates late endosome to lysosome fusion in macrophages

Syntaxin 11 (Stx11) is a SNARE protein enriched in cells of the immune system. Loss or mutation of Stx11 results in familial hemophagocytic lymphohistiocytosis type-4 (FHL-4), an autosomal recessive disorder of immune dysregulation characterized by high levels of inflammatory cytokines along with defects in T-cell and natural killer cell function. We show here Stx11 is located on endosomalmembranes including late endosomes and lysosomes in macrophages. While Stx11 did not form a typical trans-SNARE complex, it did bind to the Q-SNARE Vti1b and was able to regulate the availability of Vti1b to form the Q-SNARE complexes Stx6/Stx7/Vtib and Stx7/Stx8/Vti1b. The mutant form of Stx11 sequestered Vti1b from forming the Q-SNARE complex that mediates late endosome to lysosome fusion. Depletion of Stx11 in activated macrophages leads to an accumulation of enlarged late endocytic compartments, increased trafficking to the cell surface and inhibition of late endosome to lysosome fusion. These phenotypes arerescued by the expression of an siRNA-resistant Stx11 construct in Stx11-depleted cells. Our results suggest that by regulating the availability of Vti1b, Stx11 regulates trafficking steps between late endosomes, lysosomes and the cell surface in macrophages.

Flightless, secreted through a late endosome/lysosome pathway, binds LPS and dampens cytokine secretion.

Flightless (Flii) is upregulated in response to wounding and has been shown to function in wound closure and scarring. In macrophages intracellular Flii negatively modulates TLR signalling and dampens cytokine production. We now show that Flii is constitutively secreted from macrophages and fibroblasts and is present in human plasma. Secretion from fibroblasts is upregulated in response to scratch wounding and LPS-activated macrophages also temporally upregulate their secretion of Flii. Using siRNA, wild-type and mutant proteins we show that Flii is secreted via a late endosomal/lysosomal pathway that is regulated by Rab7 and Stx11. Flii contains 11 leucine rich repeat (LRR) domains in its N-terminus that have nearly 50% similarity to those in the extracellular pathogen binding portion of Toll-like receptor 4 (TLR4). We show secreted Flii can also bind LPS and has the ability to alter macrophage activation. LPS activation of macrophages in Flii depleted conditioned media leads to enhanced macrophage activation and increased TNF secretion compared to cells activated in the presence of Flii. These results show secreted Flii binds to LPS and in doing so alters macrophage activation and cytokine secretion, suggesting that like the intracellular pool of Flii, secreted Flii also has the ability to alter inflammation.

Lysosomal secretion of Flightless I upon injury has the potential to alter inflammation

Intracellular Flightless I (Flii), a gelsolin family member, has been found to have roles modulating actin regulation, transcriptional regulation and inflammation. In vivo Flii can regulate wound healing responses. We have recently shown that a pool of Flii is secreted by fibroblasts and macrophages, cells typically found in wounds, and its secretion can be upregulated upon wounding. We show that secreted Flii can bind to the bacterial cell wall component lipopolysaccharide and has the potential to regulate inflammation. We now show that secreted Flii is present in both acute and chronic wound fluid.

The doctrine of command responsibility in the midst of war : legal fallacy or reflection of reality

The history of war is blighted with astonishing reminders of man’s ability to cast his sense of humanity aside and inflict unspeakable harm upon one another. The ruthless bombing of Dresden, the callousness of the Nazi concentration camps and the massacre of the Tutsis are but a few of the atrocities that have haunted our past. In response to these atrocities, society has imposed an ever-increasing number of laws and rules to regulate warfare. Amongst these is the doctrine of command responsibility. The doctrine of command responsibility states that a commander is criminally liable for the crimes of his subordinates if he knew or should have known of their crimes. This paper will examine whether the doctrine is an appropriate and realistic legal standard to hold commanders accountable to or whether the doctrine is more a reflection of social sentiment and legal rhetoric. If the doctrine, and indeed the law of war in general, is unrealistic then the law cannot fulfil its purpose - that is, the prevention of atrocities. Instead of being solely a reflection of moral authority and social sentiments the law must also be a tool that guides and shapes the decisions and actions of the military through the chaotic and brutal nature of war...