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"Murphy, Fiona"
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[...]remember,\" he said, his voice faint and rushed, as if he had been forced to include the rule by the university's legal team. The research team are measuring my ability to keep track of time. Unsettled by the vertigo of firesh grief, I close the book and slip it back into the plastic bag. Bythe time we arrived at the hospital, I had gotten used to Henri saying this again and again: I insist. By now I knew not to interrupt him, knowing that he would, once again, launch into a diatribe about the 'scientifie method\" and the importance of \"field research that pushes the bounds of human physiology.\"
Journal Article
Direct Provision, Rights and Everyday Life for Asylum Seekers in Ireland during COVID-19
This article considers the impact of COVID-19 on international protection applicants in the Irish asylum system. It presents a critical reflection on the failings of direct provision and how the experience of COVID-19 has further heightened the issues at stake for asylum seekers and refugees living in Ireland. In Ireland, international protection applicants are detained in a system of institutionalized living called direct provision where they must remain until they receive status. Direct provision centres offer substandard accommodation and are often overcrowded. During the pandemic, many asylum seekers could not effectively socially isolate, so many centres experienced COVID-19 outbreaks. This article examines these experiences and joins a community of scholars calling for the urgent end to the system of direct provision.
Journal Article
Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma
The unique hazard posed to the pleural mesothelium by asbestos has engendered concern in potential for a similar risk from high aspect ratio nanoparticles (HARN) such as carbon nanotubes. In the course of studying the potential impact of HARN on the pleura we have utilised the existing hypothesis regarding the role of the parietal pleura in the response to long fibres. This review seeks to synthesise our new data with multi-walled carbon nanotubes (CNT) with that hypothesis for the behaviour of long fibres in the lung and their retention in the parietal pleura leading to the initiation of inflammation and pleural pathology such as mesothelioma. We describe evidence that a fraction of all deposited particles reach the pleura and that a mechanism of particle clearance from the pleura exits, through stomata in the parietal pleura. We suggest that these stomata are the site of retention of long fibres which cannot negotiate them leading to inflammation and pleural pathology including mesothelioma. We cite thoracoscopic data to support the contention, as would be anticipated from the preceding, that the parietal pleura is the site of origin of pleural mesothelioma. This mechanism, if it finds support, has important implications for future research into the mesothelioma hazard from HARN and also for our current view of the origins of asbestos-initiated pleural mesothelioma and the common use of lung parenchymal asbestos fibre burden as a correlate of this tumour, which actually arises in the parietal pleura.
Journal Article
Vascular smooth muscle cells enhance immune/vascular interplay in a 3-cell model of vascular inflammation
Atherosclerosis is a serious cardiovascular disease that is characterised by the development of atheroma, which are lipid-laden plaques that build up within arterial walls due to chronic inflammatory processes. These lesions are fundamentally attributed to a complex cellular crosstalk between vascular smooth muscle cells (VSMCs), vascular endothelial cells (VECs) and central immune cells, such as macrophages (Mɸs), which promote vascular inflammation. The presence of VSMCs exerts both positive and negative effects during atheroma development, which can be attributed to their phenotypic plasticity. Understanding the interactions between these key cell types during the development of vascular inflammation and atheroma will enhance the scope for new therapeutic interventions. This study aims to determine the importance of VSMCs for shaping the extracellular cytokine/chemokine profile and transcriptional responses of VECs (human coronary artery endothelial cells; HCAECs) to activated lipopolysaccharide (LPS)-stimulated THP1 Mɸs, in a 3-cell model of human vascular inflammation. It is evident that within the presence of VSMCs, enhanced cytokine production was associated with up-regulation of genes associated with vascular inflammation t. Results demonstrate that the presence of VSMCs in co-culture experiments enhanced cytokine production (including CXCL1/GROα, IL-6, IL-8 and CCL2/MCP1) and inflammatory gene expression (including genes involved in JAK/STAT, Jun and NFκB signalling) in HCAECs co-cultured with LPS-stimulated THP1 Mɸs. Our results highlight the importance of VSMCs in immune/endothelial cell interplay and indicate that 3-cell, rather than 2-cell co-culture, may be more appropriate for the study of cellular crosstalk between immune and vascular compartments in response to inflammatory and atherogenic stimuli.
Journal Article
The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells
Carbon nanotubes (CNT) are high aspect ratio nanoparticles with diameters in the nanometre range but lengths extending up to hundreds of microns. The structural similarities between CNT and asbestos have raised concern that they may pose a similar inhalation hazard. Recently CNT have been shown to elicit a length-dependent, asbestos-like inflammatory response in the pleural cavity of mice, where long fibres caused inflammation but short fibres did not. However the cellular mechanisms governing this response have yet to be elucidated. This study examined the in vitro effects of a range of CNT for their ability to stimulate the release of the acute phase cytokines; IL-1β, TNFα, IL-6 and the chemokine, IL-8 from both Met5a mesothelial cells and THP-1 macrophages. Results showed that direct exposure to CNT resulted in significant cytokine release from the macrophages but not mesothelial cells. This pro-inflammatory response was length dependent but modest and was shown to be a result of frustrated phagocytosis. Furthermore the indirect actions of the CNT were examined by treating the mesothelial cells with conditioned media from CNT-treated macrophages. This resulted in a dramatic amplification of the cytokine release from the mesothelial cells, a response which could be attenuated by inhibition of phagocytosis during the initial macrophage CNT treatments. We therefore hypothesise that long fibres elicit an inflammatory response in the pleural cavity via frustrated phagocytosis in pleural macrophages. The activated macrophages then stimulate an amplified pro-inflammatory cytokine response from the adjacent pleural mesothelial cells. This mechanism for producing a pro-inflammatory environment in the pleural space exposed to long CNT has implications for the general understanding of fibre-related pleural disease and design of safe nanofibres.
Journal Article
Fleshing Out the Invisible: Activating Social Empathy Through the Material
This article begins with the material—objects that hold stories, reveal histories, and provoke sensibilities. Ordinary Treasures: Objects From Home is a short film that foregrounds these materialities as a form of everyday activism (Chatterton & Pickerill, 2010), tracing how displaced individuals become visible through what they hold dear. In this cinematic work, international protection applicants and refugees craft an evocative narrative around the singular object each brought from home, invoking “thick solidarity” (Liu & Shange, 2018; Maillot et al., 2023). It is the material—small, mundane, yet profoundly resonant—that animates these narratives and disrupts the apparent divide between what is visible and what is not. The film’s anonymous participants emerge in fragments: hands in motion, shadows cast, voices layering against a backdrop of an original score that samples their stories. This fragmented presence centres both the material and the relationality at its core, revealing the co‐presence of the visible and the unseen, of the tangible and the unspoken. Motivated by rising anti‐immigrant rhetoric in Ireland (Vieten & Poynting, 2022), the film seeks to cultivate “relationships of discomfort” (Boudreau Morris, 2016), unsettling the frames of ignorance and challenging the boundary work of exclusion. This article aims to examine the materialities evoked by the film, the processes of their cinematic articulation, and their impact on audiences. Anchored in shared imaginings, co‐creation, and a desire to foster social empathy, Ordinary Treasures becomes an uneasy yet vital form of solidarity (Roediger, 2016). It stands as a creative interruption, offering an alternative vision of everyday activism in an Ireland grappling with the rise of populism. In this article, we will trace how these materialities themselves give rise to theoretical frameworks, shaping and reshaping our understanding of their entanglements. These are not static systems but emergent dynamics, unsettling assumptions and holding space for new solidarities to form.
Journal Article
Differential axonal trafficking of Neuropeptide Y-, LAMP1-, and RAB7-tagged organelles in vivo
Different organelles traveling through neurons exhibit distinct properties in vitro, but this has not been investigated in the intact mammalian brain. We established simultaneous dual color two-photon microscopy to visualize the trafficking of Neuropeptide Y (NPY)-, LAMP1-, and RAB7-tagged organelles in thalamocortical axons imaged in mouse cortex in vivo. This revealed that LAMP1- and RAB7-tagged organelles move significantly faster than NPY-tagged organelles in both anterograde and retrograde direction. NPY traveled more selectively in anterograde direction than LAMP1 and RAB7. By using a synapse marker and a calcium sensor, we further investigated the transport dynamics of NPY-tagged organelles. We found that these organelles slow down and pause at synapses. In contrast to previous in vitro studies, a significant increase of transport speed was observed after spontaneous activity and elevated calcium levels in vivo as well as electrically stimulated activity in acute brain slices. Together, we show a remarkable diversity in speeds and properties of three axonal organelle marker in vivo that differ from properties previously observed in vitro.
Journal Article
Rabphilin-3A negatively regulates neuropeptide release, through its SNAP25 interaction
Neuropeptides and neurotrophins are stored in and released from dense core vesicles (DCVs). While DCVs and synaptic vesicles (SVs) share fundamental SNARE/SM proteins for exocytosis, a detailed understanding of DCV exocytosis remains elusive. We recently identified the RAB3-RIM1 pathway to be essential for DCV, but not SV exocytosis, highlighting a significant distinction between the SV and DCV secretory pathways. Whether RIM1 is the only RAB3 effector that is essential for DCV exocytosis is currently unknown. In this study, we show that rabphilin-3A (RPH3A), a known downstream effector of RAB3A, is a negative regulator of DCV exocytosis. Using live-cell imaging at single-vesicle resolution with RPH3A deficient hippocampal mouse neurons, we show that DCV exocytosis increased threefold in the absence of RPH3A. RAB3A-binding deficient RPH3A lost its punctate distribution, but still restored DCV exocytosis to WT levels when re-expressed. SNAP25-binding deficient RPH3A did not rescue DCV exocytosis. In addition, we show that RPH3A did not travel with DCVs, but remained stationary at presynapses. RPH3A null neurons also had longer neurites, which was partly restored when ablating all regulated secretion with tetanus neurotoxin. Taken together, these results show that RPH3A negatively regulates DCV exocytosis, potentially also affecting neuron size. Furthermore, RAB3A interaction is required for the synaptic enrichment of RPH3A, but not for limiting DCV exocytosis. Instead, the interaction of RPH3A with SNAP25 is relevant for inhibiting DCV exocytosis.
Journal Article