Age-related changes in reticulospinal contributions to anticipatory postural adjustments between back extensors and abdominal muscles

Anticipatory postural adjustments (APAs) give feedforward postural control of the trunk, but they are delayed with ageing, affecting balance and mobility in older individuals. The reticulospinal tract contributes to postural control of the trunk; however, the extent to which age-related changes affect the reticulospinal contributions to APAs of the trunk remains unknown in humans. Here, we tested the hypothesis that a startling acoustic sound, which activates the reticulospinal tract, improves delayed APAs in older individuals. Twenty-two old (75 ± 6 years) and 20 healthy young adults (21 ± 4 years) performed a self-initiated fast bilateral shoulder flexion or shoulder extension task in response to visual, visual and auditory (80 dB), or visual and startling (115 dB) cues. Electromyography (EMG) was recorded from bilateral anterior deltoid (AD) and erector spinae (ES) during shoulder flexion and from bilateral posterior deltoid (PD) and rectus abdominis (RA) during shoulder extension. EMG onset of all muscles shortened during the startling cue in both age groups, suggesting a non-specific modulation of the reticulospinal tract on prime movers (AD or PD) and non-prime movers (ES or RA). Interestingly, APAs of the ES were accelerated in older participants to a similar degree as in younger participants during the startling cue. Conversely, APAs of the RA were not influenced by the startling cue in older participants. Our results suggest differential effects of ageing on functional contributions of the reticulospinal tract to APAs between back extensors and abdominal muscles.</p

Hospital corridors as lived spaces: The reconfiguration of social boundaries during the early stages of the Covid pandemic

This article explores the meanings and uses of a hospital corridor through 98 diary entries produced by the staff of an English specialist hospital during the early stages of the COVID‐19 pandemic. Drawing on Lefebvre's (1991, The production of space. Blackwell) threefold theorisation of space, corridors are seen as conceived, perceived and lived spaces, produced through and enabling the reconfiguration and reinterpretation of social interactions. The diaries depict two distinct versions of the central hospital corridor: its ‘normal’ operation prior to the pandemic when it was perceived as a social and symbolic space for collective sensemaking and the ‘COVID‐19 empty corridor’ described as a haunting place that divided hospital staff along ostensibly new social and moral boundaries that impacted negatively on lived work experiences and staff relationships. The mobilisation of the central hospital corridor in the daily social construction of meaning and experience during a period of organisational and societal crisis suggests that corridors should not be only seen as a material backdrop for work relationships but as social entities that come into being and are maintained and reproduced through the (lack of) performance of social relations

Detection and quantification of antibody to SARS CoV 2 receptor binding domain provides enhanced sensitivity, specificity and utility

Accurate and sensitive detection of antibody to SARS-CoV-2 remains an essential component of the pandemic response. Measuring antibody that predicts neutralising activity and the vaccine response is an absolute requirement for laboratory-based confirmatory and reference activity.The viral receptor binding domain (RBD) constitutes the prime target antigen for neutralising antibody. A double antigen binding assay (DABA), providing the most sensitive format has been exploited in a novel hybrid manner employing a solid-phase S1 preferentially presenting RBD, coupled with a labelled RBD conjugate, used in a two-step sequential assay for detection and measurement of antibody to RBD (anti-RBD).This class and species neutral assay showed a specificity of 100 % on 825 pre COVID-19 samples and a potential sensitivity of 99.6 % on 276 recovery samples, predicting quantitatively the presence of neutralising antibody determined by pseudo-type neutralization and by plaque reduction. Anti-RBD is also measurable in ferrets immunised with ChadOx1 nCoV-19 vaccine and in humans immunised with both AstraZeneca and Pfizer vaccines. This assay detects anti-RBD at presentation with illness, demonstrates its elevation with disease severity, its sequel to asymptomatic infection and its persistence after the loss of antibody to the nucleoprotein (anti-NP). It also provides serological confirmation of prior infection and offers a secure measure for seroprevalence and studies of vaccine immunisation in human and animal populations.The hybrid DABA also displays the attributes necessary for the detection and quantification of anti-RBD to be used in clinical practice. An absence of detectable anti-RBD by this assay predicates the need for passive immune prophylaxis in at-risk patients

PLK1 inhibition dampens NLRP3 inflammasome–elicited response in inflammatory disease models

Unabated activation of the NLR family pyrin domain–containing 3 (NLRP3) inflammasome is linked with the pathogenesis of various inflammatory disorders. Polo-like kinase 1 (PLK1) has been widely studied for its role in mitosis. Here, using both pharmacological and genetic approaches, we demonstrate that PLK1 promoted NLRP3 inflammasome activation at cell interphase. Using an unbiased proximity-dependent biotin identification (Bio-ID) screen for the PLK1 interactome in macrophages, we show an enhanced proximal association of NLRP3 with PLK1 upon NLRP3 inflammasome activation. We further confirmed the interaction between PLK1 and NLRP3 and identified the interacting domains. Mechanistically, we show that PLK1 orchestrated the microtubule-organizing center (MTOC) structure and NLRP3 subcellular positioning upon inflammasome activation. Treatment with a selective PLK1 kinase inhibitor suppressed IL-1β production in in vivo inflammatory models, including LPS-induced endotoxemia and monosodium urate–induced peritonitis in mice. Our results uncover a role of PLK1 in regulating NLRP3 inflammasome activation during interphase and identify pharmacological inhibition of PLK1 as a potential therapeutic strategy for inflammatory diseases with excessive NLRP3 inflammasome activation.This work was supported by British Heart Foundation (BHF) fellowship grants (FS/14/28/30713 and FS/SBSRF/22/31036, to XL); a BHF project grant (PG/17/69/33229, to XL); a BHF PhD studentship (FS/17/5/32531, to XL); and a Cambridge BHF Centre of Research Excellence grant (RE/18/1/34212). MB was supported by a BHF PhD studentship (BHF FS/17/5/32531). CD was supported by a BHF 4-year PhD student programme (FS/16/53/32729). EW was supported by a BHF project grant (PG/17/69/33229). ZM is supported by a BHF chair grant (CH/10/001/27642). The BR team was supported by the Region Centre Val de Loire (2003-00085470) and the Conseil Général du Loiret and the European Regional Development Fund (FEDER no. 2016-00110366 and EX005756). CB was supported by a Wellcome Trust Investigator Award (108045/Z/15/Z). This research was supported by the Cambridge NIHR BRC Cell Phenotyping Hub. We thank Mike Deery, Renata Feret, and Konstantin Barylyuk at the Cambridge Centre for Proteomics.Peer reviewe

Sensemaking in the early stages of the Covid-19 pandemic: a narrative exploration of polarised morality in an NHS Trust

This paper presents an analysis of personal diaries kept by healthcare staff within a specialist NHS Trust in England during the opening three months of the Covid-19 pandemic. It adopts a moral sensemaking perspective to explore how NHS employees mobilised and reframed ideas of right and wrong in order to make sense of unprecedented uncertainty and displacement. By focusing on how the macro and micro politics of the pandemic were played out in the organisation, the study finds that polarised moral judgements were invoked in order to justify and rationalise a broad array of associated emergent emotions, intuitions, behaviours and practices. This polarization of moral responses could be seen as a desire to bring order out of chaos and put matters back into place following displacement. This is inevitably an ongoing, complex and variegated enterprise whose results can as often be discomforting as they can be reassuring. Indeed, while moral sensemaking was partly beneficial for staff in that it promoted a greater sense of camaraderie and support for others, it also appeared to have darker consequences in terms of staff wellbeing and the development of more impermeable social boundaries across the organisation through processes of moral ‘othering’

Hospital corridors as lived spaces: the reconfiguration of social boundaries during the early stages of the Covid pandemic

This article explores the meanings and uses of a hospital corridor through 98 diary entries produced by the staff of an English specialist hospital during the early stages of the COVID‐19 pandemic. Drawing on Lefebvre's (1991, The production of space. Blackwell) threefold theorisation of space, corridors are seen as conceived, perceived and lived spaces, produced through and enabling the reconfiguration and reinterpretation of social interactions. The diaries depict two distinct versions of the central hospital corridor: its ‘normal’ operation prior to the pandemic when it was perceived as a social and symbolic space for collective sensemaking and the ‘COVID‐19 empty corridor’ described as a haunting place that divided hospital staff along ostensibly new social and moral boundaries that impacted negatively on lived work experiences and staff relationships. The mobilisation of the central hospital corridor in the daily social construction of meaning and experience during a period of organisational and societal crisis suggests that corridors should not be only seen as a material backdrop for work relationships but as social entities that come into being and are maintained and reproduced through the (lack of) performance of social relations

Dynamical modelling of ATLAS3D^{\rm 3D} galaxies

Triaxial dynamical models of massive galaxies observed in the ATLAS3D project can provide new insights into the complex evolutionary processes that shape galaxies. The ATLAS3D survey is ideal as the sample comprises a good mix of fast and slow rotators with vastly different mass assembly histories. We present a detailed dynamical study with our triaxial modelling code DYNAMITE, which models galaxies as a superposition of their stellar orbits. The models allow us to constrain the intrinsic shape of the stellar component, the distributions of the visible and invisible matter and the orbit distribution in these nearby early-type galaxies and to relate it with different evolutionary scenarios. Triaxial modelling is essential for these galaxies to understand their complex kinematical features.Comment: 4 pages, 3 figures, Proceeding of IAU Symposium 379: Dynamical Masses of Local Group galaxies, ed. P. Bonifacio, M.-R. Cioni, F. Hammer, M. Pawlowski, and S. Taib

Expression of human CD46 and trans-complementation by murine adenovirus 1 fails to allow productive infection by a group B oncolytic adenovirus in murine cancer cells

Abstract Background Oncolytic viruses are currently experiencing accelerated development in several laboratories worldwide, with some forty-seven clinical trials currently recruiting. Many oncolytic viruses combine targeted cytotoxicity to cancer cells with a proinflammatory cell lysis. Due to their additional potential to express immunomodulatory transgenes, they are also often known as oncolytic viral vaccines. However, several types of oncolytic viruses are human-specific and the lack of suitable immune-competent animal models complicates biologically relevant evaluation of their vaccine potential. This is a particular challenge for group B adenoviruses, which fail to infect even those immunocompetent animal model systems identified as semi-permissive for type 5 adenovirus. Here, we aim to develop a murine cell line capable of supporting replication of a group B oncolytic adenovirus, enadenotucirev (EnAd), for incorporation into a syngeneic immunocompetent animal model to explore the oncolytic vaccine potential of group B oncolytic viruses. Methods Transgenic murine cell lines were infected with EnAd expressing GFP transgene under replication-independent or -dependent promoters. Virus mRNA expression, genome replication, and late protein expression were determined by qRT-PCR, qPCR, and immunoblotting, respectively. We also use Balb/c immune-competent mice to determine the tumourogenicity and infectivity of transgenic murine cell lines. Results Our results show that a broad range of human carcinoma cells will support EnAd replication, but not murine carcinoma cells. Murine cells can be readily modified to express surface human CD46, one of the receptors for group B adenoviruses, allowing receptor-mediated uptake of EnAd particles into the murine cells and expression of CMV promoter-driven transgenes. Although the early E1A mRNA was expressed in murine cells at levels similar to human cells, adenovirus E2B and Fibre mRNA expression levels were hampered and few virus genomes were produced. Unlike previous reports on group C adenoviruses, trans-complementation of group B adenoviruses by co-infection with mouse adenovirus 1 did not rescue replication. A panel of group B adenoviruses expressing individual mouse adenovirus 1 genes were also unable to rescue EnAd replication. Conclusion Together, these results indicate that there may be major differences in the early stages of replication of group C and B adenoviruses in murine cells, and that the block to the life cycle of B adenoviruses in murine cells occurs in the early stage of virus replication, perhaps reflecting poor activity of Ad11p E1A in murine cells

Effective conservation of subterranean-roosting bats

Bats frequently inhabit caves and other subterranean habitats and play a critical role in subterranean food webs. With escalating threats to subterranean ecosystems, identifying the most effective measures to protect subterranean-roosting bats is critical. We conducted a meta-analysis to evaluate the effectiveness of conservation and management interventions for subterranean-roosting bats. We used network analyses to determine to what extent interventions for bats overlap those used for other subterranean taxa. We conducted our analyses with data extracted from 345 papers recommending a total of 910 conservation interventions. Gating of roost entrances was applied to preserve bat populations in 21 studies, but its effectiveness was unclear. Habitat restoration and disturbance reduction positively affected bat populations and bat behavior, respectively, in =4 studies. Decontamination was assessed in 2 studies and positively affected bat populations, particularly in studies focused on reducing fungal spores associated with white-nose syndrome in North America. Monitoring of bat populations as an effective conservation strategy was unclear and infrequently tested. Only 4% of bat studies simultaneously considered other subterranean organisms. However, effective interventions for bat conservation had similarities with all other organisms. If other subterranean organisms are considered when applying interventions to conserve bats, they might also benefit.Peer reviewe