Building Utopia: Performance and the Fantasy of Urban Renewal in Contemporary Toronto

Toronto markets itself as a city in renewal, a “creative city” of the future full of arts and culture. Alongside the official pitch, a number of street-level underground initiatives reimagine Toronto\u27s utopic future in a different way by means of site-specific performances

Prolonged Activation of Virus-Specific CD8(+)T Cells after Acute B19 Infection

BACKGROUND: Human parvovirus B19 (B19) is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The phenotype of CD8(+) T cells in acute B19 infection has not been studied previously. METHODS AND FINDINGS: The number and phenotype of B19-specific CD8(+) T cell responses during and after acute adult infection was studied using HLA–peptide multimeric complexes. Surprisingly, these responses increased in magnitude over the first year post-infection despite resolution of clinical symptoms and control of viraemia, with T cell populations specific for individual epitopes comprising up to 4% of CD8(+) T cells. B19-specific T cells developed and maintained an activated CD38(+) phenotype, with strong expression of perforin and CD57 and downregulation of CD28 and CD27. These cells possessed strong effector function and intact proliferative capacity. Individuals tested many years after infection exhibited lower frequencies of B19-specific cytotoxic T lymphocytes, typically 0.05%–0.5% of CD8(+) T cells, which were perforin, CD38, and CCR7 low. CONCLUSION: This is the first example to our knowledge of an “acute” human viral infection inducing a persistent activated CD8(+) T cell response. The likely explanation—analogous to that for cytomegalovirus infection—is that this persistent response is due to low-level antigen exposure. CD8(+) T cells may contribute to the long-term control of this significant pathogen and should be considered during vaccine development

A spatially heterogeneous network-based metapopulation software model applied to the simulation of a pulmonary tuberculosis infection

This work was supported by the PreDiCT-TB consortium (IMI Joint undertaking grant agreement number 115337, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution.Tuberculosis (TB) is an ancient disease that, although curable, still accounts for over 1 million deaths worldwide. Shortening treatment time is an important area of research but is hampered by the lack of models that mimic the full range of human pathology. TB shows distinct localisations during different stages of infection, the reasons for which are poorly understood. Greater understanding of how heterogeneity within the human lung influences disease progression may hold the key to improving treatment efficiency and reducing treatment times. In this work, we present a novel in silico software model which uses a networked metapopulation incorporating both spatial heterogeneity and dissemination possibilities to simulate a TB infection over the whole lung and associated lymphatics. The entire population of bacteria and immune cells is split into a network of patches: members interact within patches and are able to move between them. Patches and edges of the lung network include their own environmental attributes which influence the dynamics of interactions between the members of the subpopulations of the patches and the translocation of members along edges. In this work, we detail the initial findings of a whole-organ model that incorporates distinct spatial heterogeneity features which are not present in standard differential equation approaches to tuberculosis modelling. We show that the inclusion of heterogeneity within the lung landscape when modelling TB disease progression has significant outcomes on the bacterial load present: a greater differential of oxygen, perfusion and ventilation between the apices and the basal regions of the lungs creates micro-environments at the apex that are more preferential for bacteria, due to increased oxygen availability and reduced immune activity, leading to a greater overall bacterial load present once latency is established. These findings suggest that further whole-organ modelling incorporating more sophisticated heterogeneities within the environment and complex lung topologies will provide more insight into the environments in which TB bacteria persist and thus help develop new treatments which are factored towards these environmental conditions.Publisher PDFPeer reviewe

The Biodiversity and Climate Change Virtual Laboratory: Where ecology meets big data

Advances in computing power and infrastructure, increases in the number and size of ecological and environmental datasets, and the number and type of data collection methods, are revolutionizing the field of Ecology. To integrate these advances, virtual laboratories offer a unique tool to facilitate, expedite, and accelerate research into the impacts of climate change on biodiversity. We introduce the uniquely cloud-based Biodiversity and Climate Change Virtual Laboratory (BCCVL), which provides access to numerous species distribution modelling tools; a large and growing collection of biological, climate, and other environmental datasets; and a variety of experiment types to conduct research into the impact of climate change on biodiversity. Users can upload and share datasets, potentially increasing collaboration, cross-fertilisation of ideas, and innovation among the user community. Feedback confirms that the BCCVL's goals of lowering the technical requirements for species distribution modelling, and reducing time spent on such research, are being met

A marking of the cricothyroid membrane with extended neck returns to correct position after neck manipulation and repositioning

Background: Emergency front of neck airway access by anaesthetists carries a high failure rate and it is recommended to identify the cricothyroid membrane before induction of anaesthesia in patients with a predicted difficult airway. We have investigated whether a marking of the cricothyroid membrane done in the extended neck position remains correct after the patient's neck has been manipulated and subsequently repositioned METHODS: The subject was first placed in the extended head and neck position and had the cricothyroid membrane identified and marked with three methods, palpation, 'laryngeal handshake' and ultrasonography and the distance from the suprasternal notch to the cricothyroid membrane was measured. The subject then moved off the table and sat on a chair and subsequently returned to the extended neck position and examinations were repeated. Results: Skin markings of all 11 subjects lay within the boundaries of the cricothyroid membrane when the subject was repositioned back to the extended neck position and the median difference between the two measurements of the distance from the suprasternal notch was 0 mm (range 0-2 mm). Conclusion: The cricothyroid membrane can be identified and marked with the subject in the extended neck position. Then the patient's position can be changed as needed, for example to the 'sniffing' neck position for conventional intubation. If a front of neck airway access is required during subsequent airway management, the patient can be returned expediently to the extended-neck position, and the marking of the centre of the membrane will still be in the correct place

The Biodiversity and Climate Change Virtual Laboratory: How Ecology and Big Data can be utilised in the fight against vector-borne diseases

Advances in computing power and infrastructure, increases in the number and size of ecological and environmental datasets, and the number and type of data collection methods, are revolutionizing the field of Ecology. To integrate these advances, virtual laboratories offer a unique tool to facilitate, expedite, and accelerate research into the impacts of climate change on biodiversity. We introduce the uniquely cloud-based Biodiversity and Climate Change Virtual Laboratory (BCCVL), which provides access to numerous species distribution modelling tools; a large and growing collection of biological, climate, and other environmental datasets, as well as a variety of experiment types to conduct research into the impact of climate change on biodiversity. Users can upload and share datasets, potentially increasing collaboration and cross-fertilisation of ideas and innovation among the user community. Feedback confirms that the BCCVL's goals of lowering the technical requirements for species distribution modelling, and reducing time spent on such research, are being met. We present a case study that illustrates the utility of the BCCVL as a research tool that can be applied to the problem of vector borne diseases and the likelihood of climate change altering their future distribution across Australia. This case study presents the preliminary results of an ensemble modelling experiment which employs multiple (15) different species distribution modelling algorithms to model the distribution of one of the main mosquito vectors of the most common vector borne disease in Australia: Ross River Virus (RRV). We use the BCCVL to do future projection of these models with future climates based on two extreme emissions scenarios, for multiple years. Our results show a large range in both the modelled current distribution, and projected future distribution, of the mosquito species studied. Most models (that were built using different algorithms) show somewhat similar current distributions of the species however there are three models that are obvious outliers. The projected models show a similar range in the distribution of the species, with some models indicating a fewer areas (and also areas with a lower probability of occurrence in specific areas) where the species is likely to be found under a climate change scenario. However, a majority of models show an expanded distribution, with some areas that have a greater probability of the occurrence of this species; this will provide a more robust indication of future distribution for policy makers and planners, than if just one or a few models had been employed. The economic and human health impact of vector borne diseases underline the importance of scientifically sound projections of the future spread of common disease vectors such as mosquitos under various climate change scenarios. This is because such information is essential for policy–makers to identify vulnerable communities and to better manage outbreaks and potential epidemics of such diseases. The BCCVL has provided the means to effectively and robustly bracket multiple sources of uncertainty in the future spread of RRV: this study focuses on two of these - the future distribution of a primary mosquito vector of the disease under two extreme scenarios of climate change. Research is underway to expand our analysis to take into account more sources of uncertainty: more vector and amplifying host species, emissions scenarios, and future climate projections from a range of different global climate model

Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis

Funder: Kennedy Trust studentshipFunder: Oxford-UCB Prize FellowshipFunder: National Institute of Health Research (NIHR) Newcastle Biomedical Research Centre at Newcastle Hospitals Foundation Trust and Newcastle University and Versus Arthritis Research into Inflammatory Arthritis Centre; ref. 22072).Funder: NIHR Birmingham BRC at the University Hospitals Birmingham NHS Foundation Trust and the University of BirminghamFunder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440Funder: National Institute for Health Research (NIHR) Oxford Biomedical Research CentreFunder: St Baldrick’s FoundationAbstract: Psoriatic arthritis (PsA) is a debilitating immune-mediated inflammatory arthritis of unknown pathogenesis commonly affecting patients with skin psoriasis. Here we use complementary single-cell approaches to study leukocytes from PsA joints. Mass cytometry demonstrates a 3-fold expansion of memory CD8 T cells in the joints of PsA patients compared to peripheral blood. Meanwhile, droplet-based and plate-based single-cell RNA sequencing of paired T cell receptor alpha and beta chain sequences show pronounced CD8 T cell clonal expansions within the joints. Transcriptome analyses find these expanded synovial CD8 T cells to express cycling, activation, tissue-homing and tissue residency markers. T cell receptor sequence comparison between patients identifies clonal convergence. Finally, chemokine receptor CXCR3 is upregulated in the expanded synovial CD8 T cells, while two CXCR3 ligands, CXCL9 and CXCL10, are elevated in PsA synovial fluid. Our data thus provide a quantitative molecular insight into the cellular immune landscape of psoriatic arthritis

Transglutaminase 2 at the Crossroads between Cell Death and Survival

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