Twenty years since ‘antibody mimics’ by molecular imprinting were first proposed: A critical perspective

In February 1993, the group of Klaus Mosbach published their milestone study in Nature where, for the first time, non-covalent molecular imprints were employed in a competitive binding assay. In this seminal piece of work, and also for the first time, they refer to molecularly imprinted polymers as being ‘antibody mimics’ and hypothesised that these synthetic materials could one day provide ‘a useful, general alternative to antibodies’. This perspective article examines how far we have come in the 20 years since this publication in terms of realising this hypothesis and poses the question of whether we actually need molecularly imprinted polymers to be a general alternative to antibodies.

XBP1 mRNA splicing triggers an autophagic response in endothelial cells through BECLIN-1 transcriptional activation

Sustained activation of X-box-binding protein 1 (XBP1) results in endothelial cell (EC) apoptosis and atherosclerosis development. The present study provides evidence that XBP1 mRNA splicing triggered an autophagic response in ECs by inducing autophagic vesicle formation and markers of autophagy BECLIN-1 and microtubule-associated protein 1 light chain 3ß (LC3-ßII). Endostatin activated autophagic gene expression through XBP1 mRNA splicing in an inositol-requiring enzyme 1a (IRE1a)-dependent manner. Knockdown of XBP1 or IRE1a by shRNA in ECs ablated endostatin-induced autophagosome formation. Importantly, data from arterial vessels from XBP1 EC conditional knock-out (XBP1eko) mice demonstrated that XBP1 deficiency in ECs reduced the basal level of LC3ß expression and ablated response to endostatin. Chromatin immunoprecipitation assays further revealed that the spliced XBP1 isoform bound directly to the BECLIN-1 promoter at the region from nt -537 to -755. BECLIN-1 deficiency in ECs abolished the XBP1-induced autophagy response, whereas spliced XBP1 did not induce transcriptional activation of a truncated BECLIN-1 promoter. These results suggest that XBP1 mRNA splicing triggers an autophagic signal pathway through transcriptional regulation of BECLIN-1.

Relativistic electron mirrors from nanoscale foils for coherent frequency upshift to the extreme ultraviolet

Reflecting light from a mirror moving close to the speed of light has been envisioned as a route towards producing bright X-ray pulses since Einstein's seminal work on special relativity. For an ideal relativistic mirror, the peak power of the reflected radiation can substantially exceed that of the incident radiation due to the increase in photon energy and accompanying temporal compression. Here we demonstrate for the first time that dense relativistic electron mirrors can be created from the interaction of a high-intensity laser pulse with a freestanding, nanometre-scale thin foil. The mirror structures are shown to shift the frequency of a counter-propagating laser pulse coherently from the infrared to the extreme ultraviolet with an efficiency >10 4 times higher than in the case of incoherent scattering. Our results elucidate the reflection process of laser-generated electron mirrors and give clear guidance for future developments of a relativistic mirror structure. 

A conceptual model and key variables for guiding supportive interventions for family caregivers of people receiving palliative care

According to the World Health Organization, the patient and family should be viewed as the "unit of care" when palliative care is required. Therefore family caregivers should receive optimal supportive care from health professionals. However, the impact of supporting a dying relative is frequently described as having negative physical and psychosocial sequalae. Furthermore, family caregivers consistently report unmet needs and there has been a dearth of rigorous supportive interventions published. In addition, comprehensive conceptual frameworks to navigate the family caregiver experience and guide intervention development are lacking. This article draws on Lazarus and Folkman's seminal work on the transactional stress and coping framework to present a conceptual model specific to family caregivers of patients receiving palliative care. A comprehensive account of key variables to aid understanding of the family caregiver experience and intervention design is provided.

The Caspase-Related Protease Separase (EXTRA SPINDLE POLES) Regulates Cell Polarity and Cytokinesis in Arabidopsis

Vesicle trafficking plays an important role in cell division, establishment of cell polarity, and translation of environmental cues to developmental responses. However, the molecular mechanisms regulating vesicle trafficking remain poorly understood. Here, we report that the evolutionarily conserved caspase-related protease separase (EXTRA SPINDLE POLES [ESP]) is required for the establishment of cell polarity and cytokinesis in Arabidopsis thaliana. At the cellular level, separase colocalizes with microtubules and RabA2a (for RAS GENES FROM RAT BRAINA2a) GTPase-positive structures. Separase facilitates polar targeting of the auxin efflux carrier PIN-FORMED2 (PIN2) to the rootward side of the root cortex cells. Plants with the radially swollen4 (rsw4) allele with compromised separase activity, in addition to mitotic failure, display isotropic cell growth, perturbation of auxin gradient formation, slower gravitropic response in roots, and cytokinetic failure. Measurements of the dynamics of vesicle markers on the cell plate revealed an overall reduction of the delivery rates of KNOLLE and RabA2a GTPase in separase-deficient roots. Furthermore, dissociation of the clathrin light chain, a protein that plays major role in the formation of coated vesicles, was slower in rsw4 than in the control. Our results demonstrate that separase is a key regulator of vesicle trafficking, which is indispensable for cytokinesis and the establishment of cell polarity.

Processing the Peace:An Interview with Teya Sepinuck

In this interview, Teya Sepinuck, the Artistic Director of Theatre of Witness reflects not only on her first two projects in Northern Ireland, but also vividly illustrates her way of working by evoking seminal moments in her previous practice. Although, she has resisted attempts to systematise the Theatre of Witness process, preferring to see it as a set of principles rather than a fixed methodology, these principles have given rise to clear guidelines that have come to govern the process through which she works. As the interview illustrates, Sepinuck, a Jewish Buddhist, has no hesitation in explaining her approach within the framework of a humanist ‘spirituality’ that explicitly deploys Judeo-Christian terminology. She invites discussion of each participant's ‘prayer-life’ and positions herself primarily as a listener rather than an interlocutor. The introduction to the interview contextualises Sepinuck's practice in relation to her previous work and other drama-based interventions in Northern Ireland. Concerns that the lack of critical distance between the tellers and their stories inhibits those who see it from freely engaging with it as they might with a fictionalised account, are also critiqued. In the interview, Sepinuck directly addresses the risk of the commodification of her work, explaining the safeguards in place to protect the participants, who have repeatedly asserted how beneficial they have found their involvement in the work to be. The sense of autonomy and empowerment that emerges from these responses represent a persuasive challenge to concerns that they are passive instruments of the Theatre of Witness process.

Nile blue-based nano-sized pH sensors for simultaneous far-red and near-infrared live bioimaging

Diblock copolymer vesicles are tagged with pH-responsive Nile Blue-based labels and used as a new type of pH-responsive colorimetric/fluorescent biosensor for far-red and near-infrared imaging of live cells. The diblock copolymer vesicles described herein are based on poly(2-(methacryloyloxy)ethyl phosphorylcholine-block-2-(diisopropylamino)ethyl methacrylate) [PMPC-PDPA]: the biomimetic PMPC block is known to facilitate rapid cell uptake for a wide range of cell lines, while the PDPA block constitutes the pH-responsive component that enables facile vesicle self-assembly in aqueous solution. These biocompatible vesicles can be utilized to detect interstitial hypoxic/acidic regions in a tumor model via a pH-dependent colorimetric shift. In addition, they are also useful for selective intracellular staining of lysosomes and early endosomes via subtle changes in fluorescence emission. Such nanoparticles combine efficient cellular uptake with a pH-responsive Nile Blue dye label to produce a highly versatile dual capability probe. This is in marked contrast to small molecule dyes, which are usually poorly uptaken by cells, frequently exhibit cytotoxicity, and are characterized by intracellular distributions invariably dictated by their hydrophilic/hydrophobic balance.

Religion and the risk of suicide: longitudinal study of over 1 million people

Background: Durkheim’s seminal historical study demonstrated that religious affiliation reduces suicide risk, but it is unclear whether this protective effect persists in modern, more secular societies.

Aims: To examine suicide risk according to Christian religious affiliation and by inference to examine underlying mechanisms for suicide risk. If church attendance is important, risk should be lowest for Roman Catholics and highest for those with no religion; if religiosity is important, then ‘conservative’ Christians should fare best.

Method: A 9-year study followed 1 106 104 people aged 16–74 years at the 2001 UK census, using Cox proportional hazards models adjusted for census-based cohort attributes.

Results: In fully adjusted models analysing 1119 cases of suicide, Roman Catholics, Protestants and those professing no religion recorded similar risks. The risk associated with conservative Christians was lower than that for Catholics (HR = 0.71, 95% CI 0.52–0.97).

Conclusions: The relationship between religious affiliation and suicide established by Durkheim may not pertain in societies where suicide rates are highest at younger ages. Risks are similar for those with and without a religious affiliation, and Catholics (who traditionally are characterised by higher levels of church attendance) do not demonstrate lower risk of suicide. However, religious affiliation is a poor measure of religiosity, except for a small group of conservative Christians, although their lower risk of suicide may be attributable to factors such as lower risk behaviour and alcohol consumption.

Bone morphogenetic proteins and their antagonists: current and emerging clinical uses

Bone morphogenetic proteins (BMPs) are members of the TGFβ superfamily of secreted cysteine knot proteins that includes TGFβ₁, nodal, activins and inhibins. BMPs were first discovered by Urist in the 1960s when he showed that implantation of demineralized bone into intramuscular tissue of rabbits induced bone and cartilage formation. Since this seminal discovery, BMPs have also been shown to play key roles in several other biological processes, including limb, kidney, skin, hair and neuronal development, as well as maintaining vascular homeostasis. The multifunctional effects of BMPs make them attractive targets for the treatment of several pathologies, including bone disorders, kidney and lung fibrosis, and cancer. This review will summarize current knowledge on the BMP signalling pathway and critically evaluate the potential of recombinant BMPs as pharmacological agents for the treatment of bone repair and tissue fibrosis in patients.

Respiratory Infections Cause the Release of Extracellular Vesicles: Implications in Exacerbation of Asthma/COPD

Background: Infection-related exacerbations of respiratory diseases are a major health concern; thus understanding the mechanisms driving them is of paramount importance. Despite distinct inflammatory profiles and pathological differences, asthma and COPD share a common clinical facet: raised airway ATP levels. Furthermore, evidence is growing to suggest that infective agents can cause the release of extracellular vesicle (EVs) in vitro and in bodily fluids. ATP can evoke the P2X7/caspase 1 dependent release of IL-1β/IL-18 from EVs; these cytokines are associated with neutrophilia and are increased during exacerbations. Thus we hypothesized that respiratory infections causes the release of EVs in the airway and that the raised ATP levels, present in respiratory disease, triggers the release of IL-1β/IL-18, neutrophilia and subsequent disease exacerbations.

Methods: To begin to test this hypothesis we utilised human cell-based assays, ex vivo murine BALF, in vivo pre-clinical models and human samples to test this hypothesis.

Results: Data showed that in a murine model of COPD, known to have increased airway ATP levels, infective challenge causes exacerbated inflammation. Using cell-based systems, murine models and samples collected from challenged healthy subjects, we showed that infection can trigger the release of EVs. When exposed to ATP the EVs release IL-1b/IL-18 via a P2X₇/caspase-dependent mechanism. Furthermore ATP challenge can cause a P2X₇ dependent increase in LPS-driven neutrophilia.

Conclusions: This preliminary data suggests a possible mechanism for how infections could exacerbate respiratory diseases and may highlight a possible signalling pathway for drug discovery efforts in this area.

Land, Popular Politics and Agrarian Violence in Late Nineteenth Century Ireland

"Land, Popular Politics and Agrarian Violence in Ireland" provides an original and insightful study of the highly formative Land War and Home Rule from a local and regional perspective. Lucey examines the emergence and development of the largest mass political mobilisation brought about in nineteenth-century Ireland in the form of the Land League, and subsequently the National League, in the south-western county of Kerry. Such an unprecedented level of local political activity was matched by an upsurge in agrarian violence and the outbreak of serious outrage, which was largely orchestrated by secret societies known as Moonlighters. In turn, this book provides an important exploration of the dynamics behind the mass political mobilisation and agrarian violence that dominated Kerry society during the 1880s. The role of Fenians, radical agrarian agitators and moderate constitutional nationalists are all examined within the county.This study has importance beyond the local and provides a range of insights into motivations behind political action and violence at an everyday level during one of the most seminal and transformative eras in the development of modern Irish history. This title is suitable for students and academics of nineteenth-century Irish history and general readers.

Two potential clinical applications of the alkaline single-cell gel electrophoresis assay .1. Human bladder washings and transitional cell carcinoma of the bladder .2. Human sperm and male infertility

Part 1: The alkaline single-cell gel electrophoresis (comet) assay was used to analyse the integrity and DNA content of exfoliated cells extracted from bladder washing specimens from 9 transitional cell carcinoma patients and 15 control patients. DNA damage, as expressed by % tail DNA and tail moment values, was observed to occur in cells from both control and bladder cancer samples. The extent of the damage was, however, found to be significantly greater in the cancer group than in the control group. Comet optical density values were also recorded for each cell analysed in the comet assay and although differences observed between tumour grades were not found to be statistically significant, the mean comet optical density value was observed to be greater in the cancer group than in the control population studied, These preliminary results suggest that the comet assay may have potential as a diagnostic tool and as a prognostic indicator in transitional cell carcinoma, Part 2: Baseline DNA damage in sperm cells from 13 normozoospermic fertile males, 17 normozoospermic infertile males and 11 asthenozoospermic infertile males were compared using a modified alkaline comet assay technique. No significant difference in the level of baseline DNA damage was observed between the 3 categories of sperm studied; however the untreated sperm cells were observed to display approximately 20% tail DNA. This is notably higher than the background DNA damage observed in somatic cells where the % tail DNA is normally less than 5%. Sperm from the 3 groups of men studied were also compared for sensitivity to DNA breakage, using the modified alkaline comet assay, following X-ray irradiations (5, 10 and 30 Gy) and hydrogen peroxide treatments (40, 100 and 200 mu M). Significant levels of X-ray-induced damage were found relative to untreated control sperm in the two infertile groups following 30 Gy irradiation. Significant damage in hydrogen peroxide-treated sperm was observed in sperm from fertile samples, at 200 mu M and in infertile samples at 100- and 200-mu M doses relative to controls. These results therefore indicate that fertile sperm samples are more resistant to X-ray- and hydrogen peroxide-induced DNA breakage than infertile samples. Further studies involving greater numbers of individuals are currently in progress to confirm these findings.

Session organiser/chair: Architecture, Infrastructure and the Making of Modern Ireland

‘A free Ireland would drain the bogs, would harness the rivers, would plant the wastes, would nationalise the railways and the waterways, would improve agriculture, would protect fisheries, would foster industries, would promote commerce, and beautify the cities …’ (Padraig Pearse, ‘From a Hermitage’, 1913)

Somewhat unusually in his often romantic writings Padraig Pearse – poet, pedagogue and revolutionary – chose to describe the future of an independent Ireland in terms of infrastructure and technological processes. Terence Brown’s locating of this excerpt at the beginning his seminal work Ireland: A Social and Cultural History 1922-2002 highlights the simultaneous and interlinking construction of both a new physical and cultural landscape for an independent modern nation. Lacking any significant industrial complex, the construction of new infrastructures in Ireland was seen throughout the 20th century as a key element in the building of the new State, just as the adoption of an international style modernism in architecture was perceived as a way to escape the colonial past. For Paul N. Edwards modernity and infrastructure are intimately connected.

‘infrastructures simultaneously shape and are shaped – in other words, co-construct – the condition of modernity. By linking macro, meso, and micro scales of time, space and social organisation, they form the stable foundation of modern social worlds’ (2003: 186).
Simultaneously omnipresent and invisible – infra means beneath – Edwards also points out that infrastructure tends only to become apparent when it is either new or broken. Interpreting the meso scale as being that of the building, this session calls for papers that critically and analytically investigate aspects of the architectures of infrastructure in 20th-century Ireland. Like the territory they explore these papers may range across scales to oscillate between a concern for the artefact and its physical landscape, and the larger, often hidden systems and networks that co-define this architecture.

Folly: Art after Architecture

FOLLY brings together Irish and international contemporary artists whose work has been inspired by iconic buildings of architectural modernism. From Eileen Gray’s seminal E1027 to Mies Van der Rohe’s restored Farnsworth House, Paul Rudolph’s demolished residences to Walter Gropius’s imagined Chicago Tribune Tower, the buildings referenced in FOLLY have had a mixed collection of fates.

Their presence in this exhibition affords them another afterlife. The qualities that make the architecture significant are played-with, exposed, re-canonised, made ambiguous, and eulogised. By creating fictional moments, questioning conventional documentation or excavating troubled histories of production, each artist invites you to think about how we experience and understand architecture today.

Distributed Sounding Art – Practices in Distributing Sound (eds. Barry Truax, Marcel Cobussen and Vincent Meelberg)

This chapter examines distributed sounding art by focusing on three key aspects that we consider essentially tied to the notion of distribution: assignment, transport and sharing. These aspects aid us in navigating through a number of nodes in a history of sounding art practices where sound becomes assigned, transported and shared between places and people. Sound or data become distributed, and in the process of distribution, meanings become assigned and altered through differing socio-cultural contexts of places and people. We have selected several works, commencing in the 1960’s as we consider this period as having produced some of the seminal works that address distribution.
We draw on works by composers, performers and sound artists and thus present a history of sounding art, which is amongst the many histories of sounding art in the 20th and 21st century.