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  • Journal article
    Guder F, Coatsworth P, Bozkurt O, Cotur Y, Collins AS-P, Olenik S, Zhou Z, Naik A, Asfour T, Gonzalez-Macia L, Chao D-Yet al., 2024,

    Time-resolved chemical monitoring of whole plant roots with printed electrochemical sensors and machine learning

    , Science Advances, Vol: 10, ISSN: 2375-2548

    Traditional single-point measurements fail to capture dynamic chemical responses of plants, which are complex, nonequilibrium biological systems. We report TETRIS (time-resolved electrochemical technology for plant root environment in situ chemical sensing), a real-time chemical phenotyping system for continuously monitoring chemical signals in the often-neglected plant root environment. TETRIS consisted of low-cost, highly scalable screen-printed electrochemical sensors for monitoring concentrations of salt, pH, and H2O2 in the root environment of whole plants, where multiplexing allowed for parallel sensing operation. TETRIS was used to measure ion uptake in tomato, kale, and rice and detected differences between nutrient and heavy metal ion uptake. Modulation of ion uptake with ion channel blocker LaCl3 was monitored by TETRIS and machine learning used to predict ion uptake. TETRIS has the potential to overcome the urgent “bottleneck” in high-throughput screening in producing high-yielding plant varieties with improved resistance against stress.

  • Journal article
    Cretois B, Bick IA, Balantic C, Gelderblom FB, Pávon-Jordán D, Wiel J, Sethi SS, Betchkal DH, Banet B, Rosten CM, Reinen TAet al., 2024,

    Snowmobile noise alters bird vocalization patterns during winter and pre-breeding season

    , Journal of Applied Ecology, Vol: 61, Pages: 340-350, ISSN: 0021-8901

    Noise pollution poses a significant threat to ecosystems worldwide, disrupting animal communication and causing cascading effects on biodiversity. In this study, we focus on the impact of snowmobile noise on avian vocalizations during the non-breeding winter season, a less-studied area in soundscape ecology. We developed a pipeline relying on deep learning methods to detect snowmobile noise and applied it to a large acoustic monitoring dataset collected in Yellowstone National Park. Our results demonstrate the effectiveness of the snowmobile detection model in identifying snowmobile noise and reveal an association between snowmobile passage and changes in avian vocalization patterns. Snowmobile noise led to a decrease in the frequency of bird vocalizations during mornings and evenings, potentially affecting winter and pre-breeding behaviours such as foraging, predator avoidance and successfully finding a mate. However, we observed a recovery in avian vocalizations after detection of snowmobiles during mornings and afternoons, indicating some resilience to sporadic noise events. Synthesis and applications: Our findings emphasize the need to consider noise impacts in the non-breeding season and provide valuable insights for natural resource managers to minimize disturbance and protect critical avian habitats. The deep learning approach presented in this study offers an efficient and accurate means of analysing large-scale acoustic monitoring data and contributes to a comprehensive understanding of the cumulative impacts of multiple stressors on avian communities.

  • Journal article
    D'Amato R, Taxiarchi C, Galardini M, Trusso A, Minuz RL, Grilli S, Somerville AGT, Shittu D, Khalil AS, Galizi R, Crisanti A, Simoni A, Müller Ret al., 2024,

    Anti-CRISPR Anopheles mosquitoes inhibit gene drive spread under challenging behavioural conditions in large cages.

    , Nat Commun, Vol: 15

    CRISPR-based gene drives have the potential to spread within populations and are considered as promising vector control tools. A doublesex-targeting gene drive was able to suppress laboratory Anopheles mosquito populations in small and large cages, and it is considered for field application. Challenges related to the field-use of gene drives and the evolving regulatory framework suggest that systems able to modulate or revert the action of gene drives, could be part of post-release risk-mitigation plans. In this study, we challenge an AcrIIA4-based anti-drive to inhibit gene drive spread in age-structured Anopheles gambiae population under complex feeding and behavioural conditions. A stochastic model predicts the experimentally-observed genotype dynamics in age-structured populations in medium-sized cages and highlights the necessity of large-sized cage trials. These experiments and experimental-modelling framework demonstrate the effectiveness of the anti-drive in different scenarios, providing further corroboration for its use in controlling the spread of gene drive in Anopheles.

  • Journal article
    Patterson C, Hazime K, Zelenay S, Davis Det al., 2024,

    Prostaglandin E₂ impacts multiple stages of the natural killer cell antitumor immune response

    , European Journal of Immunology, Vol: 54, ISSN: 0014-2980

    Tumor immune escape is a major factor contributing to cancer progression and unresponsiveness to cancer therapies. Tumors can produce prostaglandin E2 (PGE2), an inflammatory mediator that directly acts on Natural killer (NK) cells to inhibit antitumor immunity. However, precisely how PGE2 influences NK cell tumor-restraining functions remains unclear. Here, we report that following PGE₂ treatment, human NK cells exhibited altered expression of specific activating receptors and a reduced ability to degranulate and kill cancer targets. Transcriptional analysis uncovered that PGE₂ also differentially modulated the expression of chemokine receptors by NK cells, inhibiting CXCR3 but increasing CXCR4. Consistent with this, PGE₂-treated NK cells exhibited decreased migration to CXCL10 but increased ability to migrate toward CXCL12. Using live cell imaging, we showed that in the presence of PGE2, NK cells were slower and less likely to kill cancer target cells following conjugation. Imaging the sequential stages of NK cell killing revealed that PGE₂ impaired NK cell polarization, but not the re-organization of synaptic actin or the release of perforin itself. Together, these findings demonstrate that PGE₂ affects multiple but select NK cell functions. Understanding how cancer cells subvert NK cells is necessary to more effectively harness the cancer-inhibitory function of NK cells in treatments.

  • Journal article
    Ahmadi Y, Umrekar TR, Mutter N, Beeby M, Barišić Iet al., 2024,

    DNA origami-enhanced binding of aptamers to Staphylococcus aureus cells

    , Biosensors and Bioelectronics: X, Vol: 16

    The combination of DNA origami nanostructures and aptamers provides a powerful technology for diagnostic assays. Here, we functionalized a DNA origami nanostructure with a Protein-A binding aptamer to target Staphylococcus aureus bacterial cells. Using an enzyme-linked oligonucleotide assay (ELONA), we semi-quantitatively analyzed and compared the interaction of the aptamer and aptamer-modified DNA origamis with Staphylococcus aureus bacterial isolates. The results showed that aptamer-functionalized DNA nanostructures bind with five times higher affinity (KD: 34 ± 5 nM) compared to the aptamer alone (KD: 160 ± 9 nM). Visualising the interaction of bacterial cells and nanostructures with electron cryotomography further confirmed the aptamer-mediated specific interaction of DNA nanostructures with bacterial cells.

  • Journal article
    Karamanos TK, Matthews S, 2024,

    Biomolecular NMR in the AI-assisted structural biology era: Old tricks and new opportunities.

    , Biochim Biophys Acta Proteins Proteom, Vol: 1872

    Over the last 40 years nuclear magnetic resonance (NMR) spectroscopy has established itself as one of the most versatile techniques for the characterization of biomolecules, especially proteins. Given the molecular size limitations of NMR together with recent advances in cryo-electron microscopy and artificial intelligence-assisted protein structure prediction, the bright future of NMR in structural biology has been put into question. In this mini review we argue the contrary. We discuss the unique opportunities solution NMR offers to the protein chemist that distinguish it from all other experimental or computational methods, and how it can benefit from machine learning.

  • Journal article
    Hatfield JH, Banks-Leite C, Barlow J, Lees AC, Tobias JAet al., 2024,

    Constraints on avian seed dispersal reduce potential for resilience in degraded tropical forests

    , Functional Ecology, Vol: 38, Pages: 315-326, ISSN: 0269-8463

    Seed dispersal is fundamental to tropical forest resilience. Forest loss or degradation typically leads to defaunation, altering seed transfer dynamics and impairing the ability of forested habitats to regenerate or recover from perturbation. However, the extent of defaunation, and its likely impacts on the seed dispersers needed to restore highly degraded or clear-felled areas, remains poorly understood in tropical forest landscapes. To quantify defaunation of seed-dispersing birds, we used field survey data from 499 transects in three forested regions of Brazil, first comparing the observed assemblages with those predicted by geographic range maps, and then assessing habitat associations of frugivores across land cover gradients. We found that current bird assemblages have lower functional diversity (FD) than predicted by species range maps in Amazonia (4%–6%), with a greater reduction in FD (28%) for the Atlantic Forest, which has been more heavily deforested for a longer period. Direct measures of seed dispersal are difficult to obtain, so we focused on potential seed transfer inferred from shared species occurrence. Of 83 predominantly frugivorous bird species recorded in relatively intact forests, we show that 10% were absent from degraded forest, and 57% absent from the surrounding matrix of agricultural land covers, including many large-gaped species. Of 112 frugivorous species using degraded forest, 47% were absent from matrix habitats. Overall, frugivores occurring in both intact forest and matrix habitats were outnumbered by (mostly small-gaped) frugivores occurring in both degraded forest and matrix habitats (23 additional species; 64% higher diversity). These findings suggest that birds have the potential to disperse seeds from intact and degraded forest to adjacent cleared lands, but that direct seed transfer from intact forests is limited, particularly for large-seeded trees. Degraded forests may play a vital role in supporting natural regenerat

  • Journal article
    Molnár Z, Aumeeruddy-Thomas Y, Babai D, Díaz S, Garnett ST, Hill R, Bates P, Brondízio ES, Cariño J, Demeter L, Fernández-Llamazares Á, Guèze M, McElwee P, Öllerer K, Purvis A, Reyes-García V, Samakov A, Singh RKet al., 2024,

    Towards richer knowledge partnerships between ecology and ethnoecology.

    , Trends Ecol Evol, Vol: 39, Pages: 109-115

    Indigenous and traditional practices based on ethnoecological knowledge are fundamental to biodiversity stewardship and sustainable use. Knowledge partnerships between Indigenous Peoples, traditional local communities, and ecologists can produce richer and fairer understandings of nature. We identify key topical areas where such collaborations can positively transform science, policy, and practice.

  • Journal article
    Cruz-Silva E, Harrion SP, Prentice IC, Marinova Eet al., 2024,

    Holocene vegetation dynamics of the Eastern Mediterranean region: old controversies addressed by a new analysis

    , Journal of Biogeography, Vol: 51, Pages: 294-310, ISSN: 0305-0270

    Aim:We reconstruct vegetation changes since 12 ky in the Eastern Mediterranean to examine four features of the regional vegetation history that are controversial: the extent of non-analogue vegetation assemblages in the transition from the Late Glacial to the early Holocene, the synchroneity of postglacial forest expansion, the geographical extent of temperate deciduous forest during the mid-Holocene and the timing and trigger for the re-establishment of drought-tolerant vegetation during the late Holocene.Location:The Eastern Mediterranean–Black Sea Caspian Corridor.Taxon:Vascular plants.Methods:We reconstruct vegetation changes for 122 fossil pollen records using a method that accounts for within-biome variability in pollen taxon abundance to determine the biome with which a sample has greatest affinity. Per-biome affinity threshold values were used to identify samples that do not belong to any modern biome. We apply time series analysis and mapping to examine space and time changes.Results:Sites with non-analogue vegetation were most common between 11.5 and 9.5 ky and mostly in the Carpathians. The transition from open vegetation to forest occurred at 10.64 ± 0.65 ky across the whole region. Temperate deciduous forest was not more extensive at 6 ky; maximum expansion occurred between 5.5 and 5 ky. Expansion of forest occurred between c. 4 and 2.8 k, followed by an abrupt decrease and a subsequent recovery. This pattern is not consistent with a systematic decline of forest towards more drought-tolerant vegetation in the late Holocene but is consistent with centennial-scale speleothem patterns linked to variations in moisture availability.Main Conclusions:We show the occurrence of non-analogue vegetation types peaked during early Holocene, forest expansion was synchronous across the region and there was an expansion of moisture-demanding temperate trees around 5.5 to 5 ky. There is no signal of a continuous late Holocene aridificat

  • Journal article
    Liu Y, Olsson A, Larva T, Cantwell-Jones A, Gill RJ, Cederberg B, Webster MTet al., 2024,

    Genomic variation in montane bumblebees in Scandinavia: high levels of intraspecific diversity despite population vulnerability.

    , Molecular Ecology, Vol: 33, ISSN: 0962-1083

    Populations of many bumblebee species are declining, with distributions shifting northwards to track suitable climates. Climate change is considered a major contributing factor. Arctic species are particularly vulnerable as they cannot shift further north, making assessment of their population viability important. Analysis of levels of whole-genome variation is a powerful way to analyse population declines and fragmentation. Here, we use genome sequencing to analyse genetic variation in seven species of bumblebee from the Scandinavian mountains, including two classified as vulnerable. We sequenced 333 samples from across the ranges of these species in Sweden. Estimates of effective population size (NE ) vary from ~55,000 for species with restricted high alpine distributions to 220,000 for more widespread species. Population fragmentation is generally very low or undetectable over large distances in the mountains, suggesting an absence of barriers to gene flow. The relatively high NE and low population structure indicate that none of the species are at immediate risk of negative genetic effects caused by high levels of genetic drift. However, reconstruction of historical fluctuations in NE indicates that the arctic specialist species Bombus hyperboreus has experienced population declines since the last ice age and we detected one highly inbred diploid male of this species close to the southern limit of its range, potentially indicating elevated genetic load. Although the levels of genetic variation in montane bumblebee populations are currently relatively high, their ranges are predicted to shrink drastically due to the effects of climate change and monitoring is essential to detect future population declines.

  • Journal article
    Mutemi DD, Tuju J, Ogwang R, Nyamako L, Wambui KM, Cruz IR, Villner P, Yman V, Kinyanjui SM, Rooth I, Ngasala B, Färnert A, Osier FHAet al., 2024,

    Antibody-dependent respiratory burst against Plasmodium falciparum Merozoites in individuals living in an area with declining malaria transmission

    , Vaccines, Vol: 12, ISSN: 2076-393X

    Malaria transmission intensity affects the development of naturally acquired immunity to malaria. An absolute correlate measure of protection against malaria is lacking. However, antibody-mediated functions against Plasmodium falciparum correlate with protection against malaria. In children, antibody-mediated functions against P. falciparum decline with reduced exposure. It is unclear whether adults maintain antibody-mediated functions as malaria transmission declines. This study assessed antibody-dependent respiratory burst (ADRB) in individuals from an area with declining malaria transmission. In an age-matched analysis, we compare ADRB activity during high versus low malaria transmission periods. Age significantly predicted higher ADRB activity in the high (p < 0.001) and low (p < 0.001) malaria transmission periods. ADRB activity was higher during the high compared to the low malaria transmission period in older children and adults. Only older adults during the high malaria transmission period had their median ADRB activity above the ADRB cut-off. Ongoing P. falciparum infection influenced ADRB activity during the low (p = 0.01) but not the high (p = 0.29) malaria transmission period. These findings propose that naturally acquired immunity to P. falciparum is affected in children and adults as malaria transmission declines, implying that vaccines will be necessary to induce and maintain protection against malaria.

  • Journal article
    Keeping T, Harrison SP, Prentice IC, 2024,

    Modelling the daily probability of wildfire occurrence in the contiguous United States

    , Environmental Research Letters, Vol: 19, ISSN: 1748-9326

    The development of a high-quality wildfire occurrence model is an essential component in mapping present wildfire risk, and in projecting future wildfire dynamics with climate and land-use change. Here, we develop a new model for predicting the daily probability of wildfire occurrence at 0.1° (∼10 km) spatial resolution by adapting a generalised linear modelling (GLM) approach to include improvements to the variable selection procedure, identification of the range over which specific predictors are influential, and the minimisation of compression, applied in an ensemble of model runs. We develop and test the model using data from the contiguous United States. The ensemble performed well in predicting the mean geospatial patterns of fire occurrence, the interannual variability in the number of fires, and the regional variation in the seasonal cycle of wildfire. Model runs gave an area under the receiver operating characteristic curve (AUC) of 0.85–0.88, indicating good predictive power. The ensemble of runs provides insight into the key predictors for wildfire occurrence in the contiguous United States. The methodology, though developed for the United States, is globally implementable.

  • Journal article
    Basu S, Shukron O, Hall D, Parutto P, Ponjavic A, Shah D, Boucher W, Lando D, Zhang W, Reynolds N, Sober LH, Jartseva A, Ragheb R, Ma X, Cramard J, Floyd R, Balmer J, Drury TA, Carr AR, Needham L-M, Aubert A, Communie G, Gor K, Steindel M, Morey L, Blanco E, Bartke T, Di Croce L, Berger I, Schaffitzel C, Lee SF, Stevens TJ, Klenerman D, Hendrich BD, Holcman D, Laue EDet al., 2024,

    Publisher Correction: Live-cell three-dimensional single-molecule tracking reveals modulation of enhancer dynamics by NuRD.

    , Nat Struct Mol Biol, Vol: 31
  • Journal article
    Leung PB, Matanza XM, Roche B, Ha KP, Cheung HC, Appleyard S, Collins T, Flanagan O, Marteyn BS, Clements Aet al., 2024,

    Shigella sonnei utilises colicins during inter-bacterial competition.

    , Microbiology (Reading), Vol: 170

    The mammalian colon is one of the most densely populated habitats currently recognised, with 1011-1013 commensal bacteria per gram of colonic contents. Enteric pathogens must compete with the resident intestinal microbiota to cause infection. Among these enteric pathogens are Shigella species which cause approximately 125 million infections annually, of which over 90 % are caused by Shigella flexneri and Shigella sonnei. Shigella sonnei was previously reported to use a Type VI Secretion System (T6SS) to outcompete E. coli and S. flexneri in in vitro and in vivo experiments. S. sonnei strains have also been reported to harbour colicinogenic plasmids, which are an alternative anti-bacterial mechanism that could provide a competitive advantage against the intestinal microbiota. We sought to determine the contribution of both T6SS and colicins to the anti-bacterial killing activity of S. sonnei. We reveal that whilst the T6SS operon is present in S. sonnei, there is evidence of functional degradation of the system through SNPs, indels and IS within key components of the system. We created strains with synthetically inducible T6SS operons but were still unable to demonstrate anti-bacterial activity of the T6SS. We demonstrate that the anti-bacterial activity observed in our in vitro assays was due to colicin activity. We show that S. sonnei no longer displayed anti-bacterial activity against bacteria that were resistant to colicins, and removal of the colicin plasmid from S. sonnei abrogated anti-bacterial activity of S. sonnei. We propose that the anti-bacterial activity demonstrated by colicins may be sufficient for niche competition by S. sonnei within the gastrointestinal environment.

  • Journal article
    Schuster M, Eisele S, Armas-Egas L, Kessenbrock T, Kourelis J, Kaiser M, van der Hoorn RALet al., 2024,

    Enhanced late blight resistance by engineering an EpiC2B-insensitive immune protease

    , Plant Biotechnology Journal, Vol: 22, Pages: 284-286, ISSN: 1467-7644

    Papain-like immune proteases (PLCPs) are promising engineering targets for crop protection, given their significant roles in plant immunity for key crops such as tomato, maize and citrus (Misas-Villamil et al., 2016). The wide range of pathogen-secreted PLCP inhibitors highlights the importance of these proteases in defending against various pathogens. Depletion of the apoplastic immune PLCP Phytophthora-inhibited protease 1 (Pip1) from tomato, for instance, causes hyper-susceptibility to bacterial, fungal and oomycete tomato pathogens (Ilyas et al., 2015). Immunity by Pip1 in wild-type tomato is, however, suboptimal since Pip1 is suppressed during infection by diverse pathogen-secreted inhibitors, such as the cystatin-like EpiC2B from the oomycete late blight pathogen Phytophthora infestans (Tian et al., 2007). Here, we tested whether we could increase Pip1-based immunity against late blight by engineering Pip1 into an EpiC2B-insensitive protease. To guide Pip1 mutagenesis, we generated a structural model of the EpiC2B-Pip1 complex using AlphaFold-Multimer (Evans et al., 2022). This structural model represents a classic interaction between the tripartite wedge of cystatin (EpiC2B) in the substrate binding groove of papain (Pip1). This model indicated that engineering Pip1 to prevent inhibition without affecting Pip1 substrate specificity is possible because the interaction surface of Pip1 with EpiC2B is larger than the substrate binding groove (Figure 1a).

  • Journal article
    Cantwell-Jones A, Tylianakis J, Larson K, Gill Ret al., 2024,

    Using individual-based trait frequency distributions to forecast plant-pollinator network responses to environmental change

    , Ecology Letters, Vol: 27, ISSN: 1461-023X

    Determining how and why organisms interact is fundamental to understanding ecosystem responses to future environmental change. To assess the impact on plant-pollinator interactions, recent studies have examined how the effects of environmental change on individual interactions accumulate to generate species-level responses. Here, we review recent developments in using plant-pollinator networks of interacting individuals along with their functional traits, where individuals are nested within species nodes. We highlight how these individual-level, trait-based networks connect intraspecific trait variation (as frequency distributions of multiple traits) with dynamic responses within plant-pollinator communities. This approach can better explain interaction plasticity, and changes to interaction probabilities and network structure over spatiotemporal or other environmental gradients. We argue that only through appreciating such trait-based interaction plasticity can we accurately forecast the potential vulnerability of interactions to future environmental change. We follow this with general guidance on how future studies can collect and analyse high-resolution interaction and trait data, with the hope of improving predictions of future plant-pollinator network responses for targeted and effective conservation.

  • Report
    Waring BG, 2024,

    The potential for enhanced soil carbon sequestration to mitigate climate change

    This briefing note assesses the potential for soil carbon sequestration to mitigate climate change, summarising the basic science and providing an overview of best practices for measuring and modifying soil carbon stocks. We also set out recommendations for policy makers, examining UK land use policies as a case study.

  • Journal article
    Li S, Waring B, Powers J, Medvigy Det al., 2024,

    Tropical dry forest response to nutrient fertilization: a model validation and sensitivity analysis

    , Biogeosciences, Vol: 21, Pages: 455-471, ISSN: 1726-4170

    Soil nutrients, especially nitrogen (N) and phosphorus (P), regulate plant growth and hence influence carbon fluxes between the land surface and atmosphere. However, how forests adjust biomass partitioning to leaves, wood, and fine roots in response to N and/or P fertilization remains puzzling. Recent work in tropical forests suggests that trees increase fine root production under P fertilization, but it is unclear whether mechanistic models can reproduce this dynamic. In order to better understand mechanisms governing nutrient effects on plant allocation and improve models, we used the nutrient-enabled ED2 model to simulate a fertilization experiment being conducted in a secondary tropical dry forest in Costa Rica. We evaluated how different allocation parameterizations affected model performance. These parameterizations prescribed a linear relationship between relative allocation to fine roots and soil P concentrations. The slope of the linear relationship was allowed to be positive, negative, or zero. Some parameterizations realistically simulated leaf, wood, and fine root production, and these parameterizations all assumed a positive relationship between relative allocation to fine roots and soil P concentration. Model simulations of a 30-year timeframe indicated strong sensitivity to parameterization and fertilization treatment. Without P fertilization, the simulated aboveground biomass (AGB) accumulation was insensitive to the parameterization. With P fertilization, the model was highly sensitive to the parameterization and the greatest AGB accumulation occurred when relative allocation to fine roots was independent of soil P. Our study demonstrates the need for simultaneous measurements of leaf, wood, and fine root production in nutrient fertilization experiments and for longer-term experiments. Models that do not accurately represent allocation to fine roots may be highly biased in their simulations of AGB, especially on multi-decadal timescales.

  • Journal article
    Wan Y, Myall AC, Boonyasiri A, Bolt F, Ledda A, Mookerjee S, Weiße AY, Getino M, Turton JF, Abbas H, Prakapaite R, Sabnis A, Abdolrasouli A, Malpartida-Cardenas K, Miglietta L, Donaldson H, Gilchrist M, Hopkins KL, Ellington MJ, Otter JA, Larrouy-Maumus G, Edwards AM, Rodriguez-Manzano J, Didelot X, Barahona M, Holmes AH, Jauneikaite E, Davies Fet al., 2024,

    Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes.

    , J Infect Dis

    BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network. METHODS: We performed a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE positive patients. Genomes of IMP-encoding CPE isolates were overlayed with patient contacts to imply potential transmission events. RESULTS: Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, E. coli); 86% (72/84) harboured an IncHI2 plasmid carrying blaIMP and colistin resistance gene mcr-9 (68/72). Phylogenetic analysis of IncHI2 plasmids identified three lineages showing significant association with patient contacts and movements between four hospital sites and across medical specialities, which was missed on initial investigations. CONCLUSIONS: Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multi-modal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks.

  • Journal article
    Worboys JD, Davis DM, 2024,

    Do inhibitory receptors need to be proximal to stimulatory receptors to function?

    , Genes Immun
  • Journal article
    Hersperger F, Meyring T, Weber P, Chhatbar C, Monaco G, Dionne MS, Paeschke K, Prinz M, Groß O, Classen A-K, Kierdorf Ket al., 2024,

    DNA damage signaling in Drosophila macrophages modulates systemic cytokine levels in response to oxidative stress

    , eLife, Vol: 12

    <jats:p>Environmental factors, infection, or injury can cause oxidative stress in diverse tissues and loss of tissue homeostasis. Effective stress response cascades, conserved from invertebrates to mammals, ensure reestablishment of homeostasis and tissue repair. Hemocytes, the <jats:italic>Drosophila</jats:italic> blood-like cells, rapidly respond to oxidative stress by immune activation. However, the precise signals how they sense oxidative stress and integrate these signals to modulate and balance the response to oxidative stress in the adult fly are ill-defined. Furthermore, hemocyte diversification was not explored yet on oxidative stress. Here, we employed high-throughput single nuclei RNA-sequencing to explore hemocytes and other cell types, such as fat body, during oxidative stress in the adult fly. We identified distinct cellular responder states in plasmatocytes, the <jats:italic>Drosophila</jats:italic> macrophages, associated with immune response and metabolic activation upon oxidative stress. We further define oxidative stress-induced DNA damage signaling as a key sensor and a rate-limiting step in immune-activated plasmatocytes controlling JNK-mediated release of the pro-inflammatory cytokine <jats:italic>unpaired-3</jats:italic>. We subsequently tested the role of this specific immune activated cell stage during oxidative stress and found that inhibition of DNA damage signaling in plasmatocytes, as well as JNK or upd3 overactivation, result in a higher susceptibility to oxidative stress. Our findings uncover that a balanced composition and response of hemocyte subclusters is essential for the survival of adult <jats:italic>Drosophila</jats:italic> on oxidative stress by regulating systemic cytokine levels and cross-talk to other organs, such as the fat body, to control energy mobilization.</jats:p>

  • Journal article
    Meccariello A, 2024,

    Gene drive and genetic sex conversion in theglobal agricultural pest Ceratitis capitata

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

    Homing-based gene drives are recently proposed interventions promising the area-wide, species-specific genetic control of harmful insect populations. Here we characterise a first set of gene drives in a tephritid agricultural pest species, the Mediterranean fruit fly Ceratitis capitata (medfly). Our results show that the medfly is highly amenable to homing-based gene drive strategies. By targeting the medfly transformer gene, we also demonstrate how CRISPR-Cas9 gene drive can be coupled to sex conversion, whereby genetic females are transformed into fertile and harmless XX males. Given this unique malleability of sex determination, we modelled gene drive interventions that couple sex conversion and female sterility and found that such approaches could be effective and tolerant of resistant allele selection in the target population. Our results open the door for developing gene drive strains for the population suppression of the medfly and related tephritid pests by co-targeting female reproduction and shifting the reproductive sex ratio towards males. They demonstrate the untapped potential for gene drives to tackle agricultural pests in an environmentally friendly and economical way.

  • Journal article
    Savolainen V, Bailey NW, Diamond L, Swift-Gallant A, Gavrilets S, Raymond M, Verweij KJHet al., 2024,

    A broader cultural view is necessary to study the evolution of sexual orientation

    , Nature Ecology and Evolution, Vol: 8, Pages: 181-183, ISSN: 2397-334X

    The causation of sexual orientation is likely to be complex and influenced by multiple factors1. We advocate incorporating a broader cultural view into evolutionary andgenetic studies to account for differences in how sexual orientation is experienced, expressed, and understood in both human and non-human animals.

  • Journal article
    Zhang X, Gao F, Ye F, Zhang B, Cronin N, Buck Met al., 2024,

    Structural basis of s54 displacement and promoter escape in bacterial transcription

    , Proceedings of the National Academy of Sciences of USA, ISSN: 0027-8424

    Gene transcription is a fundamental cellular process carried out by RNA polymerase (RNAP). Transcription initiation is highly regulated and in bacteria, transcription initiation is mediated by sigma (σ) factors. σ recruits RNAP to the promoter DNA region, located upstream oftranscription start site (TSS), and facilitates open complex formation, where double stranded DNA is opened up into a transcription bubble and template strand DNA is positioned inside RNAP for initial RNA synthesis. During initial transcription, RNAP remains bound to sigma andupstream DNA, presumably with an enlarging transcription bubble. The release of RNAP fromupstream DNA is required for promoter escape and processive transcription elongation. Bacteria sigma factors can be broadly separated into two classes with the majority belonging to the σ70 class, represented by the σ70 that regulates housekeeping genes. σ54 forms a class on its own and regulates stress response genes. Extensive studies on σ70 have revealed the molecularmechanisms of σ70 dependent process while how σ54 transitions from initial transcription to elongation is currently unknown. Here we present a series of cryo electron microscopy structures of the RNAP-σ54 initial transcribing complexes with progressively longer RNA, which reveal structural changes that lead to promoter escape. Our data show that initially, the transcription bubble enlarges, DNA strands scrunch, reducing the interactions between σ54 and DNA strands in the transcription bubble. RNA extension and further DNA scrunching help to release RNAP from σ54 and upstream DNA, enabling the transition to elongation.

  • Journal article
    Grob A, Enrico Bena C, Di Blasi R, Pessina D, Sood M, Yunyue Z, Bosia C, Isalan M, Ceroni Fet al., 2024,

    Mammalian cell growth characterisation by a non-invasive plate reader assay

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

    Automated and non-invasive mammalian cell analysis is currently lagging behind due to a lack of methods suitable for a variety of cell lines and applications. Here, we report the development of a high throughput non-invasive method for tracking mammalian cell growth and performance based on plate reader measurements. We show the method to be suitable for both suspension and adhesion cell lines, and we demonstrate it can be adopted when cells are grown under different environmental conditions. We establish that the method is suitable to inform on effective drug treatments to be used depending on the cell line considered, and that it can support characterisation of engineered mammalian cells over time. This work provides the scientific community with an innovative approach to mammalian cell screening, also contributing to the current efforts towards high throughput and automated mammalian cell engineering.

  • Book chapter
    Prentice IC, Cowling SA, 2024,

    Dynamic Global Vegetation Models

    , Encyclopedia of Biodiversity, Third Edition: Volume 1-7

    Dynamic global vegetation models encapsulate our knowledge of plant and ecosystem function. They have many potential applications but not all of these are well developed, and large differences among model predictions are a concern. Fields of application include analysis of land–atmosphere biophysical interactions, carbon and water cycling, climate impacts on vegetation structure, fire, atmospheric trace gas composition, Quaternary vegetation and environmental changes, and ecosystem structure and function through Earth history. There is scope to improve models using a wider range of information from plant functional ecology, ecophysiology, environmental remote sensing, and atmospheric measurement, Quaternary paleoecology, and paleobotany.

  • Book chapter
    McArthur HCW, Bajur AT, Spillane KM, 2024,

    Quantifying force-mediated antigen extraction in the B cell immune synapse using DNA-based tension sensors

    , Methods in Cell Biology

    B cells exert pulling forces against antigen-presenting cells (APCs) to extract antigens for internalization. The application of tugging forces on B cell receptor (BCR)-antigen bonds promotes discrimination of antigen affinities and sensing of APC physical properties. Here, we describe a protocol for preparing antigen-functionalized DNA tension sensors for quantifying force-mediated antigen extraction in the B cell immune synapse. We describe how to attach the sensors to planar lipid bilayers, quantify their surface density, use them to stimulate B cell activation, and analyze the efficiency of antigen extraction in fixed cells by fluorescence microscopy and image analysis. These techniques should be broadly applicable to studies of force-mediated transfer of molecules in cell-cell contacts.

  • Journal article
    Howes B, González-Suárez M, Banks-Leite C, Bellotto-Trigo FC, Betts MGet al., 2024,

    A global latitudinal gradient in the proportion of terrestrial vertebrate forest species

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

    Aim: Global patterns in species distributions such as the latitudinal biodiversity gradient are of great interest to ecologists and have been thoroughly studied. Whether such a gradient holds true for the proportion of species associated with key ecotypes such as forests is however unknown. Identifying a gradient and ascertaining the factors causing it could further our understanding of community sensitivity to deforestation and uncover drivers of habitat specialization. The null hypothesis is that proportions of forest species remain globally consistent, though we hypothesize that proportions will change with differences in ecotype amount, spatial structure, and environmental stability. Here we study whether the proportion of forest species follows a latitudinal gradient, and test hypotheses for why this may occur. Location: Worldwide. Time period: Present. Major taxa studied: Terrestrial vertebrates. Methods: We combined range maps and habitat use data for all terrestrial vertebrates to calculate the proportion of forest species in an area. We then used data on the global distribution of current, recent historical, and long-term historical forest cover, as well as maps of global disturbances and plant diversity to test our hypotheses using generalized linear models. Results: We identified a latitudinal gradient in the proportion of forest species whereby the highest proportions occurred at the equator and decreased polewards. We additionally found that the proportion of forest species increased with current forest cover, historical deforestation, plant structural complexity, and habitat stability. Despite the inclusion of these variables, the strong latitudinal gradient remained, suggesting additional causes of the gradient. Main conclusions: Our findings suggest that the global distribution of the proportion of forest species is a result of recent ecological, as well as long-term evolutionary factors. Interestingly, high proportions of forest species were found i

  • Journal article
    Sugiura M, Kimura M, Shimamoto N, Nakamura M, Koyama K, Selles J, Boussac A, Rutherford Aet al., 2024,

    Tuning of the ChlD1 and ChlD2 properties in photosystem II by site-directed mutagenesis of neighbouring amino acids

    , BBA: Bioenergetics, Vol: 1865, ISSN: 0005-2728

    Photosystem II is the water/plastoquinone photo-oxidoreductase of photosynthesis. The photochemistry and catalysis occur in a quasi-symmetrical heterodimer, D1D2, that evolved from a homodimeric ancestor. Here, we studied site-directed mutants in PSII from the thermophilic cyanobacterium Thermosynechoccocus elongatus, focusing on the primary electron donor chlorophyll a in D1, ChlD1, and on its symmetrical counterpart in D2, ChlD2, which does not play a direct photochemical role. The main conserved amino acid specific to ChlD1 is D1/T179, which H-bonds the water ligand to its Mg2+, while its counterpart near ChlD2 is the non-H-bonding D2/I178. The symmetrical-swapped mutants, D1/T179I and D2/I178T, and a second ChlD2 mutant, D2/I178H, were studied. The D1 mutations affected the 686 nm absorption attributed to ChlD1, while the D2 mutations affected a 663 nm feature, tentatively attributed to ChlD2. The mutations had little effect on enzyme activity and forward electron transfer, reflecting the robustness of the overall enzyme function. In contrast, the mutations significantly affected photodamage and protective mechanisms, reflecting the importance of redox tuning in these processes. In D1/T179I, the radical pair recombination triplet on ChlD1 was shared onto a pheophytin, presumably PheD1 and the detection of 3PheD1 supports the proposed mechanism for the anomalously short lifetime of 3ChlD1; e.g. electron transfer quenching by QA− of 3PheD1 after triplet transfer from 3ChlD1. In D2/I178T, a charge separation could occur between ChlD2 and PheD2, a reaction that is thought to occur in ancestral precursors of PSII. These mutants help understand the evolution of asymmetry in PSII.

  • Journal article
    Seddon C, Frankel G, Beis K, 2024,

    Structure of the outer membrane porin OmpW from the pervasive pathogen Klebsiella pneumoniae

    , Acta Crystallographica Section F: Structural Biology and Crystallization Communications Online, Vol: 80, Pages: 22-27, ISSN: 1744-3091

    Conjugation is the process by which plasmids, including those that carry antibiotic-resistance genes, are mobilized from one bacterium (the donor) to another (the recipient). The conjugation efficiency of IncF-like plasmids relies on the formation of mating-pair stabilization via intimate interactions between outer membrane proteins on the donor (a plasmid-encoded TraN isoform) and recipient bacteria. Conjugation of the R100-1 plasmid into Escherichia coli and Klebsiella pneumoniae (KP) recipients relies on pairing between the plasmid-encoded TraNα in the donor and OmpW in the recipient. Here, the crystal structure of K. pneumoniae OmpW (OmpWKP) is reported at 3.2 Å resolution. OmpWKP forms an eight-stranded β-barrel flanked by extracellular loops. The structures of E. coli OmpW (OmpWEC) and OmpWKP show high conservation despite sequence variability in the extracellular loops.

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