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Pasteurisation temperatures effectively inactivate influenza A viruses in milk
No full textIn late 2023 an H5N1 lineage of high pathogenicity avian influenza virus (HPAIV) began circulating in American dairy cattle Concerningly, high titres of virus were detected in cows’ milk, raising the concern that milk could be a route of human infection. Cows’ milk is typically pasteurised to render it safe for human consumption, but the effectiveness of pasteurisation on influenza viruses in milk was uncertain. To assess this, here we evaluate heat inactivation in milk for a panel of different influenza viruses. This includes human and avian influenza A viruses (IAVs), an influenza D virus that naturally infects cattle, and recombinant IAVs carrying contemporary avian or bovine H5N1 glycoproteins. At pasteurisation temperatures of 63°C and 72°C, we find that viral infectivity is rapidly lost and becomes undetectable before the times recommended for pasteurisation (30 minutes and 15 seconds, respectively). We then show that an H5N1 HPAIV in milk is effectively inactivated by a comparable treatment, even though its genetic material remains detectable. We conclude that pasteurisation conditions should effectively inactivate H5N1 HPAIV in cows’ milk, but that unpasteurised milk could carry infectious influenza viruses
Queer methods and pedagogies in Conal McStravick’s Learning in a Public Medium
No full textThis article considers the queer methods and pedagogies in Conal McStravick’s artist research project Learning in a Public Medium (2015–2018). The project considered the life and legacies of the late artist, educator, and writer, Stuart Marshall (1947–1993). Learning in a Public Medium exists within a lattice of contemporary artworks, projects, and research, undertaken predominantly by queer, trans, and non-binary artists, that engage LGBTQ+ archives and histories. McStravick’s project is exemplary of a queer historiographic practice that activates an ongoing relationship to past pedagogues through a public process of education. The emotions, feelings, and pull of the moment of the HIV/AIDS crisis of the late 1980s and early 1990s, commutes and transfers within the archive and artworks of Marshall, and the pedagogies of McStravick. Learning in a Public Medium staged an intra- and intergenerational mode of learning, to reflect on the remarkable legacy of Marshall and his deeply felt loss to AIDS-related illness. In the wake of another pandemic, and an increasingly hostile environment in the UK and internationally towards queer and trans communities, Learning in a Public Medium sought out tools and strategies from a past moment of pandemic and persecution, as a means of building political alliances and affinities in the present
Unraveling the transcriptomic landscape of brain vascular cells in dementia:A systematic review
No full textINTRODUCTION: Cerebrovascular dysfunction plays a critical role in the pathogenesis of dementia and related neurodegenerative disorders. Recent omics-driven research has revealed associations between vascular abnormalities and transcriptomic alterations in brain vascular cells, particularly endothelial cells (ECs) and pericytes (PCs). However, the impact of these molecular changes on dementia remains unclear.METHODS: We conducted a comparative analysis of gene expression in ECs and PCs across neurodegenerative conditions, including Alzheimer's disease (AD), Huntington's disease, and arteriovenous malformation, utilizing transcriptomic data from published postmortem human tissue studies.RESULTS: We identified differentially expressed genes (DEGs) consistently dysregulated in ECs and PCs across these pathologies. Notably, several DEGs are linked to vascular cell zonation and genetic risks for AD and cerebral small vessel disease.DISCUSSION: Our findings provide insights into the cellular and molecular mechanisms underlying vascular dysfunction in dementia, highlight the knowledge gaps, and suggest potential novel vascular therapeutic targets, including genes not previously investigated in this context.HIGHLIGHTS: Systematic review of differentially expressed genes (DEGs) in vascular cells from neurodegenerative single-nuclear RNA-sequencing (snRNA-seq) studies. Identify overlapping DEGs in multiple vascular cell types across studies. Examine functional relevance and associations with genetic risk for common DEGs. Outline future directions for the vascular omics field.</p
Endothelial cells as key players in cerebral small vessel disease
Get PDFCerebral small vessel disease (SVD) is a vascular disorder that increases the risk of stroke and dementia and is diagnosed through brain MRI. Current primary prevention and secondary treatment of SVD are focused on lifestyle interventions and vascular risk factor control, including blood pressure reduction. However, these interventions have limited effects, a proportion of individuals with sporadic SVD do not have hypertension, and SVD shows strong familial and genetic underpinnings. Here, we describe the increasing evidence that cerebral endothelial cell dysfunction is a key mechanism of SVD. Dysfunctional endothelial cells can cause cerebral blood vessel dysfunction, alter blood-brain barrier integrity and interfere with cell-cell interactions in the neuro-glial-vascular unit, thereby causing damage to adjacent brain tissue. Endothelial cells in SVD may become dysfunctional through intrinsic mechanisms via genetic vulnerability to SVD and/or via extrinsic factors such as hypertension, smoking and diabetes. Drugs that act on endothelial pathways are already looking promising in clinical trials, and understanding their action on endothelial cells and the surrounding brain may lead to the development of other therapies to limit disease progression and improve outcomes for individuals with SVD.</p
Last-millennium volcanic forcing and climate response using SO2 emissions
No full textClimate variability in the last millennium (past 1000 years) is dominated by the effects of large-magnitude volcanic eruptions; however, a long-standing mismatch exists between model-simulated and tree-ring-derived surface cooling. Accounting for the self-limiting effects of large sulfur dioxide (SO2) injections and the limitations in tree-ring records, such as lagged responses due to biological memory, reconciles some of the discrepancy, but uncertainties remain, particularly for the largest tropical eruptions. The representation of volcanic forcing in the latest generation of climate models has improved significantly, but most models prescribe the aerosol optical properties rather than using SO2 emissions directly and including interactions between the aerosol, chemistry, and dynamics. Here, we use the UK Earth System Model (UKESM) to simulate the climate of the last millennium (1250–1850 CE) using volcanic SO2 emissions. Averaged across all large-magnitude eruptions, we find similar Northern Hemisphere (NH) summer cooling compared with other last-millennium climate simulations from the Paleoclimate Modelling Intercomparison Project Phase 4 (PMIP4), run with both SO2 emissions and prescribed forcing, and a continued overestimation of surface cooling compared with tree-ring reconstructions. However, for the largest-magnitude tropical eruptions in 1257 (Mt. Samalas) and 1815 (Mt. Tambora), some models, including UKESM1, suggest a smaller NH summer cooling that is in better agreement with tree-ring records. In UKESM1, we find that the simulated volcanic forcing differs considerably from the PMIP4 dataset used in models without interactive aerosol schemes, with marked differences in the hemispheric spread of the aerosol, resulting in lower forcing in the NH when SO2 emissions are used. Our results suggest that, for the largest tropical eruptions, the spatial distribution of aerosol can account for some of the discrepancies between model-simulated and tree-ring-derived cooling. Further work should therefore focus on better resolving the spatial distribution of aerosol forcing for past eruptions
A randomised double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression (the PAX-BD study)
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Unravelling fracture plugging behavior of granular temporary plugging agents for a sustainable geothermal development
Get PDFGeothermal energy is vital for the global energy transition due to its sustainability and low environmental impact. Hydraulic fracturing is key to using unconventional underground energy, and temporary plugging and diverting fracturing (TPDF) is a promising avenue for hydraulic fracturing due to its high energy extraction efficiency. A major challenge in TPDF is forming a strong fracture plugging zone using temporary plugging agents (TPAs). However, the plugging behavior of TPAs and how they handle pressure in changing fracture widths are poorly understood. This research aims to provide effective experimental and theoretical support for the field application of TPDF technology in the development of geothermal energy. To address this, we developed a dynamic fracture width plugging simulation device to model the dynamic fracture plugging process accurately. By analyzing pressure, fracture displacement curves, and plugging zone structures from experiments, we gained insights into the failure mechanisms of the plugging zone and the behavior of dynamic fractures. Our results show three stages in the formation process of dynamic fracture plugging zones: transport, bridging, and plugging. Ineffective plugging in dynamic fractures includes “mouth sealing,” ineffective bridging, inadequate accumulation and filling, and weak mechanical strength. Plugging zone failures are categorized as local structural failure and overall structural failure. Improving the pressure-bearing capacity of dynamic fracture plugging zones can be achieved by optimizing the particle size distribution and concentration of TPAs, and by choosing the right TPA type and carrier fluid injection rate. These findings provide a basis for the optimization and design of TPDF technology, which is vital for geothermal energy extraction.</p
Germ cell quantification in human fetal and prepubertal testis tissues – a comparison of current methodologies
Get PDFNovel repair of bolted composite joints using 3D printed continuous fibre patches with custom fibre paths
Get PDFExtending the service life of composite structures often involves various repair techniques, particularly for thermoset composites, which require specialised approaches. Given the rising significance of bolted composite joints in assembling composite structures, evaluating their repairability has become increasingly important. This study presents a novel approach for repairing deformed bolt holes in mechanically fastened thermoset composite plates, which are commonly considered as non-reusable under service conditions. The approach involves utilizing 3D printing techniques to custom-fabricate bespoke continuous carbon fibre patches, with specifically tailored shapes, to restore bolt holes in thermoset material systems to their original dimensions and functionality. Two repair configurations were proposed to investigate the enhancement of mechanical performance. This customized solution not only recovers mechanical properties to a certain degree but also significantly enhances its resistance to initial damage, specifically increasing the initial strength by up to 60.79% and the initial fracture energy absorption by up to 205.01%, compared to the original specimen. A multi-scale finite element (FE) model was applied to illustrate post-repair failure mechanisms, incorporating the LaRC05 criterion for predicting intralaminar failure and a cohesive model for simulating interlaminar failure. Furthermore, comparative analysis through mechanical tests, X-ray micro-computed tomography (micro-CT) characterisation and finite element (FE) modelling demonstrates that the continuous fibre repair patch, designed based on finite element analysis, significantly outperforms simpler, geometrically based paths in overall repair efficacy. This improvement is achieved by strategically designing the fibre to endure varying stress conditions across different regions, resulting in an additional recovery of initial peak strength, ultimate strength, initial fracture energy and ultimate fracture energy absorption by 32.69%, 11.11%, 130.59% and 25.09% respectively, compared to simpler, geometrically based paths.<br/
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