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  • Journal article
    Tung NWH, Edmondson C, Westrupp N, Rosenthal M, Davies JCet al., 2024,

    Neutrophil-to-lymphocyte ratio as a biomarker of acute pulmonary exacerbations in children with cystic fibrosis: a retrospective cohort study

    , Archives of Disease in Childhood, ISSN: 0003-9888

    <jats:sec><jats:title>Background</jats:title><jats:p>Neutrophils are key contributors to chronic airway inflammation in cystic fibrosis (CF) lung disease, although airway and blood-based neutrophil markers are seldom used. The neutrophil-to-lymphocyte ratio (NLR) is an accessible biomarker, the clinical utility of which has not been adequately studied.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>This study aimed to investigate the characteristics of the NLR in children with CF and its correlations with acute pulmonary exacerbations and spirometry.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>A previous study had collected clinical data from children with CF for a 3-year period between 2016 and 2021. Retrospectively, NLR values were categorised according to patients’ clinical status during blood sample collection as ‘stable’, ‘acute pulmonary exacerbation’ or ‘elective admission for chronic clinical concern’.</jats:p></jats:sec><jats:sec><jats:title>Main outcome measures</jats:title><jats:p>Demographic characteristics associated with the NLR; changes in NLR values in relation to clinical status; relationship between NLR and lung function.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>141 children with CF were included. NLR values during clinical stability were higher in females and increased with age. For children admitted for intravenous antibiotics, NLR values significantly increased from clinical stability (median (IQR)=1.13 (0.75–1.51)) to acute pulmonary exacerbations (median (IQR)=1.50 (0.96–2.65), p=0.001), but similar changes were not observed in elective admissions. The NLR was not associated with lung function.</jats:p></jats:sec><jats:sec><jats:t

  • Journal article
    Hai D, Li J, Jiang D, Cheng J, Fu Y, Xiao X, Yin H, Lin Y, Chen T, Li B, Yu X, Cai Q, Chen W, Kotta-Loizou I, Xie Jet al., 2024,

    Plants interfere with non-self recognition of a phytopathogenic fungus via proline accumulation to facilitate mycovirus transmission

    , Nature Communications, Vol: 15, ISSN: 2041-1723

    Non-self recognition is a fundamental aspect of life, serving as a crucial mechanism for mitigating proliferation of molecular parasites within fungal populations. However, studies investigating the potential interference of plants with fungal non-self recognition mechanisms are limited. Here, we demonstrate a pronounced increase in the efficiency of horizontal mycovirus transmission between vegetatively incompatible Sclerotinia sclerotiorum strains in planta as compared to in vitro. This increased efficiency is associated with elevated proline concentration in plants following S. sclerotiorum infection. This surge in proline levels attenuates the non-self recognition reaction among fungi by inhibition of cell death, thereby facilitating mycovirus transmission. Furthermore, our field experiments reveal that the combined deployment of hypovirulent S. sclerotiorum strains harboring hypovirulence-associated mycoviruses (HAVs) together with exogenous proline confers substantial protection to oilseed rape plants against virulent S. sclerotiorum. This unprecedented discovery illuminates a novel pathway by which plants can counteract S. sclerotiorum infection, leveraging the weakening of fungal non-self recognition and promotion of HAVs spread. These promising insights provide an avenue to explore for developing innovative biological control strategies aimed at mitigating fungal diseases in plants by enhancing the efficacy of horizontal HAV transmission.

  • Journal article
    Wang X, Kotta-Loizou I, Coutts RHA, Deng H, Han Z, Hong N, Shafik K, Wang L, Guo Y, Yang M, Xu W, Wang Get al., 2024,

    A circular single-stranded dna mycovirus infects plants and confers broad-spectrum resistance against fungal diseases

    , Molecular Plant, Vol: 17, Pages: 955-971, ISSN: 1674-2052

    Circular single-stranded (ss) DNA viruses have been rarely found in fungi, and the evolutionary and ecological relationships among ssDNA viruses infecting fungi and other organisms remain unclear. Here, a novel circular ssDNA virus, tentatively named Diaporthe sojae circular DNA virus 1 (DsCDV1), was identified in the phytopathogenic fungus Diaporthe sojae isolated from pear trees. DsCDV1 has a monopartite genome (3,185 nt in size) encapsidated in isometric virions (21-26 nm in diameter). The genome comprises seven putative open reading frames encoding a discrete replicase (Rep) split by an intergenic region, a putative capsid protein (CP), several proteins of unknown function (P1 to P4), and a long intergenic region. Notably, the two split parts of DsCDV1 Rep share high identities with the Reps of Geminiviridae and Genomoviridae, respectively, indicating an evolutionary linkage with both families. Phylogenetic analysis based on Rep or CP sequences placed DsCDV1 in a unique cluster, supporting the establishment of a new family, tentatively named Gegemycoviridae, intermediate to both families. DsCDV1 significantly attenuates fungal growth and nearly erases virulence when transfected into the host fungus. Remarkably, DsCDV1 can systematically infect tobacco and pear seedlings, providing broad-spectrum resistance to fungal diseases. Subcellular localization analysis revealed that P3 systematically localizes in plasmodesmata, while and its expression in trans-complementation experiments restores the wild-type phenotype of a movement-deficient plant virus; thus P3 is identified as a movement protein. DsCDV1 exhibits unique molecular and biological traits not observed in other ssDNA viruses, serving as a link between fungal and plant ssDNA viruses and presenting an evolutionary connection between ssDNA viruses and fungi. These findings contribute to expanding our understanding of ssDNA virus diversity and evolution, offering potential biocontrol applications for managing

  • Journal article
    Jiang Q, Otáhalová V, Burré V, Leese HS, Shaffer MSP, Hahn R, Menner A, Bismarck Aet al., 2024,

    Variable capacity polymer based energy harvesters with integrated macroporous elastomer springs

    , Nano Energy, Vol: 124, ISSN: 2211-2855

    We introduce a manufacturing concept of variable capacity energy harvesters consisting of macroporous springs integrated within a conducting silicone rubber and dielectric. Printing and polymerising emulsion templates resulted in macroporous spring elements, which were coated with conducting silicone rubber to maintain the active contact surface. By increasing size and number of these springs, the capacitance change of the energy harvesters during compression and recovery increased from 0.4 nF/cm2 to 0.8 nF/cm2. During cyclic loading with 30 N at 2 Hz, the energy harvesters with macroporous springs delivered a power density of 0.58 µW/cm2 at a bias voltage of 50 V, which was 25 times higher than the control without springs. The energy harvesters provided a constant power output over three hours of cyclic loading (21,600 cycles), indicating their structural stability and the durability of the macroporous springs.

  • Journal article
    Wisnom MR, Pimenta S, Shaffer MSP, Robinson P, Potter KD, Hamerton I, Czél G, Jalalvand M, Fotouhi M, Anthony DB, Yu H, Longana ML, Wu X, Bismarck Aet al., 2024,

    High performance ductile and pseudo-ductile polymer matrix composites: a review

    , Composites Part A: Applied Science and Manufacturing, Vol: 181, ISSN: 1359-835X

    The ability of fibre reinforced composites to deform with a non-linear stress–strain response and gradual, rather than sudden, catastrophic failure is reviewed. The principal mechanisms by which this behaviour can be achieved are discussed, including ductile fibres, progressive fibre fracture and fragmentation, fibre reorientation, and slip between discontinuous elements. It is shown that all these mechanisms allow additional strain to be achieved, enabling a yield-like behaviour to be generated. In some cases, the response is ductile and in others pseudo-ductile. Mechanisms can also be combined, and composites which give significant pseudo-ductile strain can be produced. Notch sensitivity is reduced, and there is the prospect of increasing design strains whilst also improving damage tolerance. The change in stiffness or visual indications of damage can be exploited to give warning that strain limits have been exceeded. Load carrying capacity is still maintained, allowing continued operation until repairs can be made. Areas for further work are identified which can contribute to creating structures made from high performance ductile or pseudo-ductile composites that fail gradually.

  • Journal article
    Delhaye G, van der Linde S, Bauman D, Orme CDL, Suz LM, Bidartondo MIet al., 2024,

    Ectomycorrhizal fungi are influenced by ecoregion boundaries across Europe

    , Global Ecology and Biogeography, Vol: 33, ISSN: 1466-822X

    AimEcoregions and the distance decay in community similarity are fundamental concepts in biogeography and conservation biology that are well supported across plants and animals, but not fungi. Here we test the relevance of these concepts for ectomycorrhizal (ECM) fungi in temperate and boreal regions.LocationEurope.Time Period2008–2015.Major Taxa StudiedEctomycorrhizal fungi.MethodsWe used a large dataset of ~24,000 ectomycorrhizas, assigned to 1350 operational taxonomic units, collected from 129 forest plots via a standardized protocol. We investigated the relevance of ecoregion delimitations for ECM fungi through complementary methodological approaches based on distance decay models, multivariate analyses and indicator species analyses. We then evaluated the effects of host tree and climate on the observed biogeographical distributions.ResultsEcoregions predict large-scale ECM fungal biodiversity patterns. This is partly explained by climate differences between ecoregions but independent from host tree distribution. Basidiomycetes in the orders Russulales and Atheliales and producing epigeous fruiting bodies, with potentially short-distance dispersal, show the best agreement with ecoregion boundaries. Host tree distribution and fungal abundance (as opposed to presence/absence only) are important to uncover biogeographical patterns in mycorrhizas.Main ConclusionsEcoregions are useful units to investigate eco-evolutionary processes in mycorrhizal fungal communities and for conservation decision-making that includes fungi.

  • Journal article
    Matthews J, Dobra R, Wilson G, Allen L, Bossley C, Brendell R, Brugha R, Brown D, Brown S, Cadiente S, Cameron L, Davies G, Dawson C, Elborn S, Hughes D, Longmate J, Macedo P, Pappas L, Pao C, Round C, Ruiz G, Saunders C, Shafi N, Simmonds N, Waller M, Watson D, Davies Jet al., 2024,

    Levelling the playing field through the London Network of the UK clinical trials accelerator platform

    , Contemporary Clinical Trials Communications, Vol: 39, ISSN: 2451-8654

    Cystic fibrosis (CF) is a multisystem, genetic disease with a significantly reduced life expectancy. Despite substantial progress in therapies in the last 10–15 years, there is still no cure. There are dozens of drugs in the development pipeline and multiple clinical trials are being conducted across the globe. The UK Cystic Fibrosis Trust's (CFT) Clinical Trials Accelerator Platform (CTAP) is a national initiative bringing together 25 UK based CF centres to support the CF community in accessing and participating in CF clinical trials. CTAP enables more CF centres to run a broader portfolio of trials and increases the range of CF studies available for UK patients.There are four large specialist CF centres based in London, all within a small geographical region as well as two smaller centres which deliver CF care. At the launch of CTAP, these centres formed a sub-network in a consortium-style collaboration. The purpose of the network was to ensure equity of access to trials for patients across the UK's capital, and to share experience and knowledge. Four years into the programme we have reviewed our practices through working group meetings and an online survey. We sought to identify strengths and areas for improvement. We share our findings here, as we believe they are relevant to others delivering research in regions outside of London and in other chronic diseases.

  • Journal article
    Ngo LT, Rekowski MJ, Koestler DC, Yorozuya T, Saito A, Azeem I, Harrison A, Demoruelle MK, Boomer J, England BR, Wolters P, Molyneaux PL, Castro M, Lee JS, Solomon JJ, Koronuma K, Washburn MP, Matson SMet al., 2024,

    Proteomic profiling of bronchoalveolar lavage fluid uncovers protein clusters linked to survival in idiopathic forms of interstitial lung disease.

    , medRxiv

    BACKGROUND: Idiopathic interstitial pneumonias (IIPs) such as idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF), present diagnostic and therapeutic challenges due to their heterogeneous nature. This study aimed to identify intrinsic molecular signatures within the lung microenvironment of these IIPs through proteomic analysis of bronchoalveolar lavage fluid (BALF). METHODS: Patients with IIP (n=23) underwent comprehensive clinical evaluation including pre-treatment bronchoscopy and were compared to controls without lung disease (n=5). Proteomic profiling of BALF was conducted using label-free quantitative methods. Unsupervised cluster analyses identified protein expression profiles which were then analyzed to predict survival outcomes and investigate associated pathways. RESULTS: Proteomic profiling successfully differentiated IIP from controls. k-means clustering, based on protein expression revealed three distinct IIP clusters, which were not associated with age, smoking history, or baseline pulmonary function. These clusters had unique survival trajectories and provided more accurate survival predictions than the Gender Age Physiology (GAP) index (C-index 0.794 vs. 0.709). The cluster with the worst prognosis featured decreased inflammatory signaling and complement activation, with pathway analysis highlighting altered immune response pathways related to immunoglobulin production and B cell-mediated immunity. CONCLUSIONS: The unsupervised clustering of BALF proteomics provided a novel stratification of IIP patients, with potential implications for prognostic and therapeutic targeting. The identified molecular phenotypes underscore the diversity within the IIP classification and the potential importance of personalized treatments for these conditions. Future validation in larger, multi-ethnic cohorts is essential to confirm these findings and to explore their utility in clinical decision-making for patients with IIP.

  • Journal article
    Quintero Santofimio V, Knox-Brown B, Potts J, Bartlett-Pestell S, Feary J, Amaral Aet al., 2024,

    Small airways obstruction and mortality: Findings from the UK Biobank

    , Chest, ISSN: 0012-3692

    Background:Small airways obstruction (SAO) is common in general populations. It has been associated with respiratory symptoms, cardiometabolic diseases and progression to chronic obstructive pulmonary disease over time. Whether SAO predicts mortality is largely unknown.Research QuestionIs spirometry-defined SAO associated with increased mortality?Methods:We analysed data from 252,877 adult participants, aged 40-69 at baseline, in the UK Biobank who had provided good quality spirometry measurements. We defined SAO as the ratio of the forced expiratory volume in three seconds to the forced expiratory volume in six seconds less than the lower limit of normal (FEV3/FEV6<LLN). We considered SAO to be isolated if present when the forced expiratory volume in one second to FEV6 ratio was normal (FEV1/FEV6≥LLN). We used a multivariable Cox regression model to assess the association of SAO, and isolated SAO, with all-cause and disease-specific mortality. We investigated sex differences in these associations and repeated the primary analysis excluding ever smokers. All models were adjusted for potential confounders such as sex, body mass index, smoking status, smoking pack-years, assessment centre, Townsend deprivation index and ethnicity.Results:We identified 59,744 participants with SAO of which 24,004 had isolated SAO. A total of 5,009 deaths were reported over a median of 12.8 years of follow-up. Participants with SAO had increased all-cause (HR=1.31, 95%CI 1.26-1.36), cardiovascular (HR=1.39, 95%CI 1.29-1.51), respiratory (HR=2.20, 95%CI 1.92-2.51), and neoplasm (HR=1.23, 95%CI 1.17-1.29) mortality risk. These associations were not modified by sex. However, in never smokers, only respiratory and cardiovascular mortality risk was associated with SAO. Isolated SAO was also associated with an increased mortality risk (HR=1.14, 95%CI 1.07-1.20).Interpretation:Individuals with SAO have an increased risk of all-cause and disease-specific mortality. Further studies are nee

  • Journal article
    Yuen ELH, Leary AY, Clavel M, Tumtas Y, Mohseni A, Zhao J, Picchianti L, Jamshidiha M, Pandey P, Duggan C, Cota E, Dagdas Y, Bozkurt TOet al., 2024,

    A RabGAP negatively regulates plant autophagy and immune trafficking.

    , Curr Biol, Vol: 34, Pages: 2049-2065.e6

    Plants rely on autophagy and membrane trafficking to tolerate stress, combat infections, and maintain cellular homeostasis. However, the molecular interplay between autophagy and membrane trafficking is poorly understood. Using an AI-assisted approach, we identified Rab3GAP-like (Rab3GAPL) as a key membrane trafficking node that controls plant autophagy negatively. Rab3GAPL suppresses autophagy by binding to ATG8, the core autophagy adaptor, and deactivating Rab8a, a small GTPase essential for autophagosome formation and defense-related secretion. Rab3GAPL reduces autophagic flux in three model plant species, suggesting that its negative regulatory role in autophagy is conserved in land plants. Beyond autophagy regulation, Rab3GAPL modulates focal immunity against the oomycete pathogen Phytophthora infestans by preventing defense-related secretion. Altogether, our results suggest that Rab3GAPL acts as a molecular rheostat to coordinate autophagic flux and defense-related secretion by restraining Rab8a-mediated trafficking. This unprecedented interplay between a RabGAP-Rab pair and ATG8 sheds new light on the intricate membrane transport mechanisms underlying plant autophagy and immunity.

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

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