Targeting translocator protein (18 kDa) (TSPO) dampens pro-inflammatory microglia reactivity in the retina and protects from degeneration

BACKGROUND: Reactive microglia are commonly seen in retinal degenerative diseases, and neurotoxic microglia responses can contribute to photoreceptor cell death. We and others have previously shown that translocator protein (18 kDa) (TSPO) is highly induced in retinal degenerations and that the selective TSPO ligand XBD173 (AC-5216, emapunil) exerts strong anti-inflammatory effects on microglia in vitro and ex vivo. Here, we investigated whether targeting TSPO with XBD173 has immuno-modulatory and neuroprotective functions in two mouse models of acute retinal degeneration using bright white light exposure.

METHODS: BALB/cJ and Cx3cr1 (GFP/+) mice received intraperitoneal injections of 10 mg/kg XBD173 or vehicle for five consecutive days, starting 1 day prior to exposure to either 15,000 lux white light for 1 h or 50,000 lux focal light for 10 min, respectively. The effects of XBD173 treatment on microglia and Müller cell reactivity were analyzed by immuno-stainings of retinal sections and flat mounts, fluorescence-activated cell sorting (FACS) analysis, and mRNA expression of microglia markers using quantitative real-time PCR (qRT-PCR). Optical coherence tomography (OCT), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stainings, and morphometric analyses were used to quantify the extent of retinal degeneration and photoreceptor apoptosis.

RESULTS: Four days after the mice were challenged with bright white light, a large number of amoeboid-shaped alerted microglia appeared in the degenerating outer retina, which was nearly completely prevented by treatment with XBD173. This treatment also down-regulated the expression of TSPO protein in microglia but did not change the TSPO levels in the retinal pigment epithelium (RPE). RT-PCR analysis showed that the microglia/macrophage markers Cd68 and activated microglia/macrophage whey acidic protein (Amwap) as well as the pro-inflammatory genes Ccl2 and Il6 were reduced after XBD173 treatment. Light-induced degeneration of the outer retina was nearly fully blocked by XBD173 treatment. We further confirmed these findings in an independent mouse model of focal light damage. Retinas of animals receiving XBD173 therapy displayed significantly more ramified non-reactive microglia and more viable arrestin-positive cone photoreceptors than vehicle controls.

CONCLUSIONS: Targeting TSPO with XBD173 effectively counter-regulates microgliosis and ameliorates light-induced retinal damage, highlighting a new pharmacological concept for the treatment of retinal degenerations.

“They should stay at their desk until the work’s done”: a qualitative study examining perceptions of sedentary behaviour in a desk-based occupational setting

Background: Workplace sedentary behaviour is a priority target for health promotion. However, little is known about how to effect change. We aimed to explore desk-based office workers’ perceptions of factors that influenced sedentary behaviour at work and to explore the feasibility of using a novel mobile phone application to track their behaviours.

Methods: We invited office employees (n = 12) and managers (n = 2) in a software engineering company to participate in semi-structured interviews to explore perceived barriers and facilitators affecting workplace sedentary behaviour. We assessed participants’ sedentary behaviours using an accelerometer before and after they used a mobile phone application to record their activities at self-selected time intervals daily for 2 weeks. Interviews were analysed using a thematic framework.

Results: Software engineers (5 employees; 2 managers) were interviewed; 13 tested the mobile phone application; 8 returned feedback. Major barriers to reducing workplace sedentary behaviour included the pressure of ‘getting the job done’, the nature of their work requiring sitting at a computer, personal preferences for the use of time at and after work, and a lack of facilities, such as a canteen, to encourage moving from their desks. Facilitators for reduced sedentariness included having a definite reason to leave their desks, social interaction and relief of physical and mental symptoms of prolonged sitting. The findings were similar for participants with different levels of overall physical activity. Valid accelerometer data were tracked for four participants: all reduced their sedentary behaviour. Participants stated that recording data using the phone application added to their day’s work but the extent to which individuals perceived this as a burden varied and was counter-balanced by its perceived value in increasing awareness of sedentary behaviour. Individuals expressed a wish for flexibility in its configuration.

Conclusions: These findings indicate that employers’ and employees’ perceptions of the cultural context and physical environment of their work, as well as personal factors, must be considered in attempting to effect changes that reduce workplace sedentary behaviour. Further research should investigate appropriate individually tailored approaches to this challenge, using a framework of behaviour change theory which takes account of specific work practices, preferences and settings.

Inside the tent: Community and government in refugee camps

Refugee camps are increasingly managed through a liberal rationality of government similar to that of many industrialized societies, with security mechanisms being used to optimize the life of particular refugee populations. This governmentality has encompassed programmes introduced by the United Nations High Commissioner for Refugees (UNHCR) and various non-governmental organizations (NGOs) to build and empower communities through the spatial technology of the camp. The present article argues that such attempts to ‘govern through community’ have been too easily dismissed or ignored. It therefore examines how such programmes work to produce, manage and conduct refugees through the use of a highly instrumentalized understanding of community in the spatial and statistical management of displaced people in camps. However, community is always both more and less than what is claimed of it, and therefore undermines attempts to use it as a governing tactic. By shifting to a more ontological understanding of community as unavoidable coexistence, inspired by Jean-Luc Nancy, we can see how the scripting of and government through community in camps is continually exceeded, redirected and resisted. Ethnographies of specific camps in Africa and the Middle East enable us both to see how the necessary sociality of being resists its own instrumentalization and to view the camp as a spatial security technology. Such resistance does not necessarily lead to greater security, but it redirects our attention to how community is used to conduct the behaviour of refugees, while also producing counter-conducts that offer greater agency, meaning and mobility to those displaced in camps.

Nonconservative current-driven dynamics: beyond the nanoscale

Long metallic nanowires combine crucial factors for nonconservative current-driven atomic motion. These systems have degenerate vibrational frequencies, clustered about a Kohn anomaly in the dispersion relation, that can couple under current to form nonequilibrium modes of motion growing exponentially in time. Such motion is made possible by nonconservative current-induced forces on atoms, and we refer to it generically as the waterwheel effect. Here the connection between the waterwheel effect and the stimulated directional emission of phonons propagating along the electron flow is discussed in an intuitive manner. Nonadiabatic molecular dynamics show that waterwheel modes self-regulate by reducing the current and by populating modes in nearby frequency, leading to a dynamical steady state in which nonconservative forces are counter-balanced by the electronic friction. The waterwheel effect can be described by an appropriate effective nonequilibrium dynamical response matrix. We show that the current-induced parts of this matrix in metallic systems are long-ranged, especially at low bias. This nonlocality is essential for the characterisation of nonconservative atomic dynamics under current beyond the nanoscale.

Accountability for Forced Displacement in Democratic Republic of Congo and Uganda before the International Criminal Court

This article examines the challenges of investigating and prosecuting forced displacement in the Central African countries of Democratic Republic of Congo and Uganda, where higher loss of life was caused by forced displacement, than by any other. In the Democratic Republic of Congo, armed groups intentionally attacked civilian populations displacing them from their homes, to cut them off from food and medical supplies. In Northern Uganda, the government engaged in a forced displacement policy as part of its counter-insurgency against the Lord’s Resistance Army, driving the civilian population into “protected villages”, where at one point the weekly death toll was over 1,000 in these camps. This article critically evaluates how criminal responsibility can be established for forced displacement and alternative approaches to accountability through reparations.

Parker Morris and the Fordist House

6.00 pm. If people like watching T.V. while they are eating their evening meal, space for a low table is needed (Ministry of Housing and Local Government, Space in the Home, 1963, p. 4).

This paper re-examines the 1961 Parker Morris report on housing standards in Britain. It explores the origins, scope, text and iconography of the report and suggests that these not only express a particularly modernist conception of space but one which presupposed very specific economic conditions and geographies.

Also known as Homes for Today and Tomorrow Parker Morris attempted, through the application of scientific principles, to define the minimum living space standards needed to accommodate household activities. But while early modernist research into notions of existenzminimum were the work of avant-garde architects and thinkers, Homes for Today and Tomorrow and its sister design manual Space in the Home were commissioned by the British State. This normalization of scientific enquiry into space can be considered not only as a response to new conditions in the mass production of housing – economies of scale, prefabrication, system-building and modular coordination – but also to the post-war boom in consumer goods. In this, it is suggested that the domestic interior was assigned a key role as a privileged site of mass consumption as the production and micro-management of space in Britain became integral to the development of a planned national economy underpinned by Fordist principles. Parker Morris, therefore, sought to accommodate activities which were pre-determined not so much by traditional social or familial ties but rather by recently introduced commodities such as the television set, white goods, table tennis tables and train sets. This relationship between the domestic interior and the national economy are emblematized by the series of placeless and scale-less diagrams executed by Gordon Cullen in Space in the Home. Here, walls dissolve as space flows from inside to outside in a homogenized and ephemeral landscape whose limits are perhaps only the boundaries of the nation state and the circuits of capital.

In Britain, Parker Morris was the last explicit State-sponsored attempt to prescribe a normative spatial programme for national living. The calm neutral efficiency of family-life expressed in its diagrams was almost immediately problematised by the rise of 1960s counter-culture, the feminist movement and the oil crisis of 1972 which altered perhaps forever the spatial, temporal and economic conditions it had taken for granted. The debate on space-standards, however, continues.

Dublin 1916: theatre of revolt

At Easter 1916, Dublin city centre was one of a series of sites throughout Ireland where a rebellion was staged against British rule. It was a strategic failure, swiftly crushed by superior British forces. The event, however, subsequently took a central role in the mythology of modern Ireland.

The first visual representations were of the conflict’s aftermath: photographic journeys through landscapes of ruin. From the distance of the camera, we see none of the pockmarks of shell bursts, nor the etchings of machine guns. Instead, traces of life in the city seem to have been swept aside by an unseen hand: the passing of millennia or a violent action of nature. Architecture alone has witnessed and recorded its presence. Amongst the fragments, the shell of the General Post Office (G.P.O.) in Sackville Street is one of the few buildings still wholly recognizable. The remnants of its classical form, portico and pediment, columns and entablature seem to transcend its prosaic modern functions and allude to something more ancient. The bewilderment of city’s inhabitants is also recorded. Dubliners have become inquisitive tourists in streets which hitherto were the locus of everyday life. They wander around aimlessly in a landscape as alien and picturesque as Pompeii. This shift in perception was captured by the Irish poet W.B. Yeats who hinted that Dublin, purged of modern commercialism had transcended its petty inadequacies to revive a slumbering heroic past.

‘I have met them at the close of day
Coming with vivid faces
From counter or desk among grey
Eighteenth-century houses [.]’
All is changed, changed utterly:
A terrible beauty is born.’

His comments were prescient. Initially unpopular, the republican leaders, executed by the British, slowly became recast as heroic martyrs. Similarly, the spaces where their heroism was forged became venerated. The G.P.O. and Sackville Street, however, already had a republican history. It was originally conceived in the eighteenth century as part of a series of magnificent urban spaces to provide an arena of spectacle and self-celebration for the colonial Anglo-Irish and their vision of a Protestant republic. O’Connell/Sackville Street became the temporal, geographical and mythical hinge upon which two different versions of Irish republicanism waxed and waned. Its recasting after independence as a space of Catholic Nationalism bore testimony to its consistency in providing a backdrop for the production of ritual and myth. In the 1920s and 30s, as the nascent country, beset with economic stagnation and political tensions, turned to spectacle as a salve for it social problems, O’Connell Street and the G.P.O. provided its most sacred sites. Within the introduction of new myths, however, individual as well as national identities were created and consolidated. The emerging identity of modern Ireland became inextricably linked with that of one ambitious politician. His uses of the G.P.O. in particular revealed a perceptive understanding of the political uses of classical architecture and urban space.

Effects of tobacco products on the attachment and growth of periodontal ligament fibroblasts

BACKGROUND: Cigarette smoking is one of the most significant risk factors in the development and further advancement of inflammatory periodontal disease, however, the role of either nicotine or its primary metabolite cotinine in the progression of periodontitis is unclear. This study aimed to investigate the effects of nicotine and cotinine on the attachment and growth of fibroblasts derived from human periodontal ligament (PDL).

METHODS: Primary cultures were prepared from the roots of extracted premolar teeth. Cells were used at both low (P3 to P5) and high (P11 to P13) passage. Cell numbers were determined over 14 days using either the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay or with a Coulter counter. Cultures were exposed to culture medium supplemented with 1) 15% fetal calf serum (FCS) only; 2) 1% FCS only; 3) 1% FCS and nicotine (concentration range 5 ng/ml to 10 mg/ml); or 4) 1% FCS and cotinine (concentration range 0.5 ng/ml to 10 microg/ml).

RESULTS: Nicotine significantly (P <0.05, by ANOVA) inhibits attachment and growth of low passage cells at concentrations >1 mg/ml and high passage PDL fibroblasts at concentrations >0.5 mg/ml. Cotinine, at the highest concentration used (10 microg/ml), appeared to inhibit attachment and growth of both low and high passage fibroblasts but this was not statistically significant (P >0.05, by ANOVA).

CONCLUSIONS: Tobacco products inhibit attachment and growth of human PDL fibroblasts. This may partly explain the role of these substances in the progression of periodontitis.

Northern Ireland

Northern Ireland has been considered a conflict-resolution success story. The 1998 Belfast/Good Friday Agreement provided a framework for managing a long-standing ethnonational conflict, and has ushered in relative political stability. The consociational features of the Northern Ireland Assembly can be seen either as necessary for managing conflict or as institutionalizing sectarianism so that politics along left–right lines cannot emerge. Although there is evidence for the development of a “Northern Irish” identity to counter competing British and Irish identities, Northern Ireland is a long way from transcending the sectarian structures that shape almost all aspects of social and political life. Northern Ireland remains segregated along religious lines and is also prone to tensions around the anniversaries of atrocities and the public use of symbols and rituals. The failure to systematically “deal with the past” through public information recovery and truth-telling mechanisms also seems to have hindered progress toward reconciliation.

Spatial variation in adult sex ratio across multiple scales in the invasive golden apple snail, Pomacea canaliculata

Adult sex ratio (ASR) has critical effects on behavior and life history and has implications for population demography, including the invasiveness of introduced species. ASR exhibits immense variation in nature, yet the scale dependence of this variation is rarely analyzed. In this study, using the generalized multilevel models, we investigated the variation in ASR across multiple nested spatial scales and analyzed the underlying causes for an invasive species, the golden apple snail Pomacea canaliculata. We partitioned the variance in ASR to describe the variations at different scales and then included the explanatory variables at the individual and group levels to analyze the potential causes driving the variation in ASR. We firstly determined there is a significant female-biased ASR for this species when accounting for the spatial and temporal autocorrelations of sampling. We found that, counter to nearly equal distributed variation at plot, habitat and region levels, ASR showed little variation at the town level. Temperature and precipitation at the region level were significantly positively associated with ASR, whereas the individual weight, the density characteristic, and sampling time were not significant factors influencing ASR. Our study suggests that offspring sex ratio of this species may shape the general pattern of ASR in the population level while the environmental variables at the region level translate the unbiased offspring sex ratio to the female-biased ASR. Future research should consider the implications of climate warming on the female-biased ASR of this invasive species and thus on invasion pattern.

Finance, social economics and community development

The last three decades have seen social enterprises in the United Kingdom pushed to the forefront of welfare delivery, workfare and area-based regeneration. For critics, this is repositioning the sector around a neoliberal politics that privileges marketization, state roll-back and disciplining community groups to become more self-reliant. Successive governments have developed bespoke products, fiscal instruments and intermediaries to enable and extend the social finance market. Such assemblages are critical to roll-out tactics, but they are also necessary and useful for more reformist understandings of economic alterity. The issue is not social finance itself but how it is used, which inevitably entangles social enterprises in a form of legitimation crises between the need to satisfy financial returns and at the same time keep community interests on board. This paper argues that social finance, how it is used, politically domesticated and achieves re-distributional outcomes is a necessary component of counter-hegemonic strategies. Such assemblages are as important to radical community development as they are to neoliberalism and the analysis concludes by highlighting the need to develop a better understanding of finance, the ethics of its use and tactical compromises in scaling it as an alternative to public and private markets.

Queering Memories of the Troubles: Performing LGBTQ testimonies in Northern Ireland

In Northern Ireland, decades of religious and political unrest led to the marginalization not only of rights but also the experiences and voices of those who identify as Lesbian, Gay, Bisexual, Trans and/or Queer (LGBTQ). The peace process has arguably created space in which sexual minorities can voice their experiences and articulate counter-memories to those that tend to dominate ethno-nationalist commemorations of the conflict. This essay explores two productions of Northern Ireland’s first publicly funded gay theatre company, TheatreofplucK, led by artistic director Niall Rea: D.R.A.G (Divided, Radical and Gorgeous) was first performed in 2011 and explores the personal experiences of a Belfast drag queen in the form of personal testimonial monologue. The forthcoming (November 2015) performed archive installation, Tr<uble, by Shannon Yee, assembles true-life testimonies of the LGBTQ community in Northern Ireland during and after the Troubles. I will explore how performed and performative memories have the potential to ‘queer’ remembrance of the Troubles.

The Extra-territorial Obligations of European States regarding Human Rights in the Context of Terrorism

This chapter focuses on the growing tendency of international human rights law to require states to protect the rights of non-nationals who are in the state unlawfully and of nationals and non-nationals who are outside the state, especially when any of these people are involved in terrorist or counter-terrorist activity. It reviews these additional obligations within a European context, focusing on EU law and the law of the European Convention on Human Rights and drawing on the case law of UK courts. Part 1 considers when a European state must grant asylum to alleged terrorists on the basis that otherwise they would suffer human rights abuses in the state from which they are fleeing. Part 2 examines whether, outside of asylum claims, a European state must not deport or extradite an alleged terrorist because he or she might suffer an abuse of human rights in the receiving state. Part 3 looks at whether a European state whose security forces are engaged in counter-terrorism activities abroad is obliged to protect the human rights of the individuals serving in those forces and/or the human rights of the alleged terrorists they are confronting. While welcoming the extension of state responsibility, the chapter notes that it is occurring in a way which introduces three aspects of relativity into the protection of human rights. First, European law protects only some human rights extra-territorially. Second, it protects those rights only when there is ‘a real risk’ of their being violated. Third, sometimes it protects those rights only when there is a real risk of their being violated ‘flagrantly’.

Síntese e estudos estruturais de novos materiais luminescentes

A presente dissertação teve como objectivo a síntese, caracterização e estudo das propriedades luminescentes de complexos livres e/ou imobilizados no material mesoporoso MCM-41. Na primeira parte estudaram-se complexos do tipo, Eu(NTA)3L2, onde NTA corresponte ao β-dicetonato 1-(2-naftoil)-3,3,3-trifluoro-acetonato, e L2 aos ligandos bidentados de azoto derivados do pirazolilpiridina e L aos ligandos monodentados (etil-4-piridilacetato, água, piridina e metilfenilsulfóxido). Alguns destes ligandos foram imobilizados e/ou impregnados no MCM-41, tendo-se posteriormente complexado o fragmento Eu(NTA)3. Na segunda parte estudou-se o efeito do contra-ião no complexo C[Eu(NTA)4], usando os catiões (C): tetrabutilamónio [NBu4]+, 1-butil-3-metilimidazolilo [C4mim]+ e 1-butil-3-metilpiridínio [C4mpy]+. O anião [Eu(NTA)4]- foi imobilizado no MCM-41 derivatizado com grupos 1-propil-3-metilimidazolilo. Todos os complexos preparados foram caracterizados pelas técnicas de análise elementar, termogravimetria, espectroscopias vibracionais (Infravermelho e Raman) e de ressonância magnética nuclear, e os materiais preparados foram adicionalmente analisados por difracção de raios-X de pós e ressonância magnética nuclear de estado sólido. Foram também estudadas as propriedades fotoluminescentes dos compostos, e para facilitar a análise dos resultados, nalguns casos foram preparados e caracterizados os compostos análogos de gadolínio.

Thick-microstructures for MPGDs: simulations and experimental studies

Cherenkov Imaging counters require large photosensitive areas, capable of single photon detection, operating at stable high gains under radioactive backgrounds while standing high rates, providing a fast response and a good time resolution, and being insensitive to magnetic fields. The development of photon detectors based in Micro Pattern Gaseous detectors (MPGDs), represent a new generation of gaseous photon detectors. In particular, gaseous detectors based on stacked Thick-Gaseous Electron Multipliers (THGEMs), or THGEM based structures, coupled to a CsI photoconverter coating, seem to fulfil the requirements imposed by Cherenkov imaging counters. This work focus on the study of the THGEM-based detectors response as function of its geometrical parameters and applied voltages and electric fields, aiming a future upgrade of the Cherenkov Imaging counter RICH-1 of the COMPASS experiment at CERN SPS. Further studies to decrease the fraction of ions that reach the photocathode (Ion Back Flow – IBF) to minimize the ageing and maximize the photoelectron extraction are performed. Experimental studies are complemented with simulation results, also perfomed in this work.