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  • Journal article
    Pang B, Cheng S, Huang Y, Jin Y, Guo Y, Prentice IC, Harrison SP, Arcucci Ret al., 2025,

    Fire-Image-DenseNet (FIDN) for predicting wildfire burnt area using remote sensing data

    , Computers and Geosciences, Vol: 195, ISSN: 0098-3004

    Predicting the extent of massive wildfires once ignited is essential to reduce the subsequent socioeconomic losses and environmental damage, but challenging because of the complexity of fire behavior. Existing physics-based models are limited in predicting large or long-duration wildfire events. Here, we develop a deep-learning-based predictive model, Fire-Image-DenseNet (FIDN), that uses spatial features derived from both near real-time and reanalysis data on the environmental and meteorological drivers of wildfire. We trained and tested this model using more than 300 individual wildfires that occurred between 2012 and 2019 in the western US. In contrast to existing models, the performance of FIDN does not degrade with fire size or duration. Furthermore, it predicts final burnt area accurately even in very heterogeneous landscapes in terms of fuel density and flammability. The FIDN model showed higher accuracy, with a mean squared error (MSE) about 82% and 67% lower than those of the predictive models based on cellular automata (CA) and the minimum travel time (MTT) approaches, respectively. Its structural similarity index measure (SSIM) averages 97%, outperforming the CA and FlamMap MTT models by 6% and 2%, respectively. Additionally, FIDN is approximately three orders of magnitude faster than both CA and MTT models. The enhanced computational efficiency and accuracy advancements offer vital insights for strategic planning and resource allocation for firefighting operations.

  • Book chapter
    Majumdar J, Biswas JK, Majumdar A, Roychowdhury T, Santra SC, Hossain A, Moulick Det al., 2025,

    Rhizomicrobiome: Role in management of heavy metal stress in plants

    , Rhizomicrobiome in Sustainable Agriculture and Environment, Publisher: Elsevier, Pages: 315-332, ISBN: 9780443236914
  • Book chapter
    Dey S, Majumdar A, Dubey PK, Roychowdhury T, Majumdar J, Santra SC, Hossain A, Moulick Det al., 2025,

    Involvement of soil parameters and rhizosphere microbiome in sustainable crop productivity

    , Rhizomicrobiome in Sustainable Agriculture and Environment, Publisher: Elsevier, Pages: 189-228, ISBN: 9780443236914
  • Journal article
    Abitbol V, Martinón-Torres F, Taha M-K, Nolan T, Muzzi A, Bambini S, Borrow R, Toneatto D, Serino L, Rappuoli R, Pizza Met al., 2024,

    4CMenB journey to the 10-year anniversary and beyond.

    , Hum Vaccin Immunother, Vol: 20

    The 4-component meningococcal serogroup B (MenB) vaccine, 4CMenB, the first broadly protective, protein-based MenB vaccine to be licensed, is now registered in more than 50 countries worldwide. Real-world evidence (RWE) from the last decade confirms its effectiveness and impact, with infant immunization programs showing vaccine effectiveness of 71-95% against invasive MenB disease and cross-protection against non-B serogroups, including a 69% decrease in serogroup W cases in 4CMenB-eligible cohorts in England. RWE from different countries also demonstrates the potential for additional moderate protection against gonorrhea in adolescents. The real-world safety profile of 4CMenB is consistent with prelicensure reports. Use of the endogenous complement human serum bactericidal antibody (enc-hSBA) assay against 110 MenB strains may enable assessment of the immunological effectiveness of multicomponent MenB vaccines in clinical trial settings. Equitable access to 4CMenB vaccination is required to better protect all age groups, including older adults, and vulnerable groups through comprehensive immunization policies.

  • Journal article
    Tong Jia Ming S, Tan Yi Jun K, Carissimo G, 2024,

    Pathogenicity and virulence of O’nyong-nyong virus: A less studied <i>Togaviridae</i> with pandemic potential

    , Virulence, Vol: 15, ISSN: 2150-5594
  • Journal article
    Efron A, Brozzi A, Biolchi A, Bodini M, Giuliani M, Guidotti S, Lorenzo F, Moscoloni MA, Muzzi A, Nocita F, Pizza M, Rappuoli R, Tomei S, Vidal G, Vizzotti C, Campos J, Sorhouet Pereira Cet al., 2024,

    Genetic characterization and estimated 4CMenB vaccine strain coverage of 284 Neisseria meningitidis isolates causing invasive meningococcal disease in Argentina in 2010-2014.

    , Hum Vaccin Immunother, Vol: 20

    Meningococcal (Neisseria meningitidis) serogroup B (MenB) strain antigens are diverse and a limited number of strains can be evaluated using the human serum bactericidal antibody (hSBA) assay. The genetic Meningococcal Antigen Typing System (gMATS) was developed to predict the likelihood of coverage for large numbers of isolates by the 4CMenB vaccine, which includes antigens Neisseria adhesin A (NadA), Neisserial Heparin-Binding Antigen (NHBA), factor H-binding protein (fHbp), and Porin A (PorA). In this study, we characterized by whole-genome analyses 284 invasive MenB isolates collected from 2010 to 2014 by the Argentinian National Laboratories Network (52-61 isolates per year). Strain coverage was estimated by gMATS on all isolates and by hSBA assay on 74 randomly selected isolates, representative of the whole panel. The four most common clonal complexes (CCs), accounting for 81.3% of isolates, were CC-865 (75 isolates, 26.4%), CC-32 (59, 20.8%), CC-35 (59, 20.8%), and CC-41/44 (38, 13.4%). Vaccine antigen genotyping showed diversity. The most prevalent variants/peptides were fHbp variant 2, NHBA peptides 24, 21, and 2, and PorA variable region 2 profiles 16-36 and 14. The nadA gene was present in 66 (23.2%) isolates. Estimated strain coverage by hSBA assay showed 78.4% of isolates were killed by pooled adolescent sera, and 51.4% and 64.9% (based on two different thresholds) were killed by pooled infant sera. Estimated coverage by gMATS (61.3%; prediction interval: 55.5%, 66.7%) was consistent with the infant hSBA assay results. Continued genomic surveillance is needed to evaluate the persistence of major MenB CCs in Argentina.

  • Journal article
    Parry C, Turnbull C, Gill R, 2024,

    Tracking pollen tube and ovule development in vivo reveals rapid responses to pollination in Brassica napus

    , Annals of Botany Plants
  • Journal article
    Sethi SS, Bick A, Chen M-Y, Crouzeilles R, Hillier BV, Lawson J, Lee C-Y, Liu S-H, Parruco CHDF, Rosten CM, Somveille M, Tuanmu M-N, Banks-Leite Cet al., 2024,

    Reply to Araújo: Good science requires focus.

    , Proc Natl Acad Sci U S A, Vol: 121
  • Journal article
    Schroeder J, Dunning J, Chan AHH, Chik HYJ, Burke Tet al., 2024,

    Not so social in old age: demography as one driver of decreasing sociality.

    , Philos Trans R Soc Lond B Biol Sci, Vol: 379

    Humans become more selective with whom they spend their time, and as a result, the social networks of older humans are smaller than those of younger ones. In non-human animals, processes such as competition and opportunity can result in patterns of declining sociality with age. While there is support for declining sociality with age in mammals, evidence from wild bird populations is lacking. Here, we test whether sociality declines with age in a wild, insular bird population, where we know the exact ages of individuals. Using 6 years of sociality data, we find that as birds aged, their degree and betweenness decreased. The number of same-age birds still alive also decreased with age. Our results suggest that a longitudinal change in sociality with age may be, in part, an emergent effect of natural changes in demography. This highlights the need to investigate the changing costs and benefits of sociality across a lifetime.This article is part of the discussion meeting issue 'Understanding age and society using natural populations'.

  • Journal article
    Jaramillo V, Hebron H, Wong S, Atzori G, Bartsch U, Dijk D-J, Violante IRet al., 2024,

    Closed-loop auditory stimulation targeting alpha and theta oscillations during rapid eye movement sleep induces phase-dependent power and frequency changes.

    , Sleep, Vol: 47

    STUDY OBJECTIVES: Alpha and theta oscillations characterize the waking human electroencephalogram (EEG) and can be modulated by closed-loop auditory stimulation (CLAS). These oscillations also occur during rapid eye movement (REM) sleep, but their function here remains elusive. CLAS represents a promising tool to pinpoint how these brain oscillations contribute to brain function in humans. Here we investigate whether CLAS can modulate alpha and theta oscillations during REM sleep in a phase-dependent manner. METHODS: We recorded high-density EEG during an extended overnight sleep period in 18 healthy young adults. Auditory stimulation was delivered during both phasic and tonic REM sleep in alternating 6-second ON and 6-second OFF windows. During the ON windows, stimuli were phase-locked to four orthogonal phases of ongoing alpha or theta oscillations detected in a frontal electrode. RESULTS: The phases of ongoing alpha and theta oscillations were targeted with high accuracy during REM sleep. Alpha and theta CLAS induced phase-dependent changes in power and frequency at the target location. Frequency-specific effects were observed for alpha trough (speeding up) and rising (slowing down) and theta trough (speeding up) conditions. CLAS-induced phase-dependent changes were observed during both REM sleep substages, even though auditory evoked potentials were very much reduced in phasic compared to tonic REM sleep. CONCLUSIONS: This study provides evidence that faster REM sleep rhythms can be modulated by CLAS in a phase-dependent manner. This offers a new approach to investigating how modulation of REM sleep oscillations affects the contribution of this vigilance state to brain function.

  • Journal article
    Rowell J, Lau C-I, Ross S, Yanez DC, Peña OA, Chain B, Crompton Tet al., 2024,

    Distinct T-cell receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymus.

    , Elife, Vol: 13

    Here, we sequenced rearranged TCRβ and TCRα chain sequences in CD4+CD8+ double positive (DP), CD4+CD8- single positive (SP4) and CD4-CD8+ (SP8) thymocyte populations from the foetus and young adult mouse. We found that life-stage had a greater impact on TCRβ and TCRα gene segment usage than cell-type. Foetal repertoires showed bias towards 3'TRAV and 5'TRAJ rearrangements in all populations, whereas adult repertoires used more 5'TRAV gene segments, suggesting that progressive TCRα rearrangements occur less frequently in foetal DP cells. When we synchronised young adult DP thymocyte differentiation by hydrocortisone treatment the new recovering DP thymocyte population showed more foetal-like 3'TRAV and 5'TRAJ gene segment usage. In foetus we identified less influence of MHC-restriction on α-chain and β-chain combinatorial VxJ usage and CDR1xCDR2 (V region) usage in SP compared to adult, indicating weaker impact of MHC-restriction on the foetal TCR repertoire. The foetal TCRβ repertoire was less diverse, less evenly distributed, with fewer non-template insertions, and all foetal populations contained more clonotypic expansions than adult. The differences between the foetal and adult thymus TCR repertoires are consistent with the foetal thymus producing αβT-cells with properties and functions that are distinct from adult T-cells: their repertoire is less governed by MHC-restriction, with preference for particular gene segment usage, less diverse with more clonotypic expansions, and more closely encoded by genomic sequence.

  • Journal article
    Yan Y, Antolin N, Zhou L, Xu L, Vargas IL, Gomez CD, Kong G, Palmisano I, Yang Y, Chadwick J, Müller F, Bull AMJ, Lo Celso C, Primiano G, Servidei S, Perrier JF, Bellardita C, Di Giovanni Set al., 2024,

    Macrophages excite muscle spindles with glutamate to bolster locomotion

    , Nature, ISSN: 0028-0836

    The stretch reflex is a fundamental component of the motor system that orchestrates the coordinated muscle contractions underlying movement. At the heart of this process lie the muscle spindles (MS), specialized receptors finely attuned to fluctuations in tension within intrafusal muscle fibres. The tension variation in the MS triggers a series of neuronal events including an initial depolarization of sensory type Ia afferents that subsequently causes the activation of motoneurons within the spinal cord1,2. This neuronal cascade culminates in the execution of muscle contraction, underscoring a presumed closed-loop mechanism between the musculoskeletal and nervous systems. By contrast, here we report the discovery of a new population of macrophages with exclusive molecular and functional signatures within the MS that express the machinery for synthesizing and releasing glutamate. Using mouse intersectional genetics with optogenetics and electrophysiology, we show that activation of MS macrophages (MSMP) drives proprioceptive sensory neuron firing on a millisecond timescale. MSMP activate spinal circuits, motor neurons and muscles by means of a glutamate-dependent mechanism that excites the MS. Furthermore, MSMP respond to neural and muscle activation by increasing the expression of glutaminase, enabling them to convert the uptaken glutamine released by myocytes during muscle contraction into glutamate. Selective silencing or depletion of MSMP in hindlimb muscles disrupted the modulation of the stretch reflex for force generation and sensory feedback correction, impairing locomotor strategies in mice. Our results have identified a new cellular component, the MSMP, that directly regulates neural activity and muscle contraction. The glutamate-mediated signalling of MSMP and their dynamic response to sensory cues introduce a new dimension to our understanding of sensation and motor action, potentially offering innovative therapeutic approaches in conditions that affect s

  • Journal article
    Tica J, Oliver Huidobro M, Zhu T, Wachter G, Pazuki R, Bazzoli D, Scholes N, Tonello E, Siebert H, Stumpf M, Endres R, Isalan Met al., 2024,

    A three-node Turing gene circuit forms periodic spatial patterns in bacteria

    , Cell Systems, ISSN: 2405-4720
  • Journal article
    Zhong Z, Hocking BJW, Brown CP, Ma T, White AJP, Mann DJ, Armstrong A, Bull JAet al., 2024,

    Synthesis and Functionalization of Sulfoximine‐Bicyclo[1.1.0]butanes: Functionalizable, Tuneable and Cysteine‐Selective Chiral Warheads

    , Angewandte Chemie, ISSN: 0044-8249

    <jats:title>Abstract</jats:title><jats:p>Electrophilic covalent warheads with appropriate reactivity and selectivity are crucial to the investigation of protein function and the discovery of therapeutics. Here we report the synthesis of sulfoximine bicyclo[1.1.0] butanes (BCBs) as novel thiol reactive chiral warheads, achieved in one‐pot from methylsulfoximines. Unusually the warhead can then be derivatized, keeping the BCB intact, over 3 vectors: i) sulfoximine N‐modification instills a broad range of strain‐release reactivity; ii) sp<jats:sup>2</jats:sup>‐cross‐coupling reactions on aryl‐BCB‐sulfoximines allows direct diversification, and iii) functionalization of the BCB motif itself is achieved by metalation and trapping with electrophiles. The BCB sulfoximines are shown to react selectively with cysteine including in a protein model (CDK2) under biocompatible conditions. Preliminary data indicate suitability for chemoproteomic applications, and enantioselective cysteine‐labelling. The reactivity of sulfoximine BCBs with electron withdrawing groups on nitrogen is comparable to acrylamides with low to moderate reactivity.</jats:p>

  • Journal article
    Sayol F, Wayman JP, Dufour P, Martin TE, Hume JP, Jørgensen MW, Martínez-Rubio N, Sanglas A, Soares FC, Cooke R, Mendenhall CD, Margolis JR, Illera JC, Lemoine R, Benavides E, Lapiedra O, Triantis KA, Pigot AL, Tobias JA, Faurby S, Matthews TJet al., 2024,

    AVOTREX: A Global Dataset of Extinct Birds and Their Traits

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

    Motivation: Human activities have been reshaping the natural world for tens of thousands of years, leading to the extinction of hundreds of bird species. Past research has provided evidence of extinction selectivity towards certain groups of species, but trait information is lacking for the majority of clades, especially for prehistoric extinctions identified only through subfossil remains. This incomplete knowledge potentially obscures the structure of natural communities, undermining our ability to infer changes in biodiversity across space and time, including trends in functional and phylogenetic diversity. Biases in currently available trait data also limit our ability to identify drivers and processes of extinction. Here we present AVOTREX, an open-access database of species traits for all birds known to have gone extinct in the last 130,000 years. This database provides detailed morphological information for 610 extinct species, along with a pipeline to build phylogenetic trees that include these extinct species. Main Types of Variables Contained: For each extinct bird species, we provide information on the taxonomy, geographic location, and period of extinction. We also present data on island endemicity, flight ability, and body mass, as well as standard measurements of external (matching the AVONET database of extant birds) and skeletal morphology from museum specimens where available. To ensure comprehensive morphological data coverage, we estimate all missing morphological measurements using a data imputation technique based on machine learning. Finally, we provide an R package to graft all extinct species onto a global phylogeny of extant species (BirdTree). Spatial Location and Grain: Global. Time Period and Grain: All known globally extinct bird species from 130,000 years ago up until 2024. Major Taxa and Level of Measurement: Birds (Class Aves), species level. Software Format: Spreadsheets (.csv) stored in Dryad.

  • Journal article
    Ewers RM, Cook J, Daniel OZ, Orme CDL, Groner V, Joshi J, Rallings A, Rallings T, Amarasekare Pet al., 2024,

    New insights to be gained from a Virtual Ecosystem

    , Ecological Modelling, Vol: 498, ISSN: 0304-3800

    The myriad interactions among individual plants, animals, microbes and their abiotic environment generate emergent phenomena that will determine the future of life on Earth. Here, we argue that holistic ecosystem models – incorporating key biological domains and feedbacks between biotic and abiotic processes and capable of predicting emergent phenomena – are required if we are to understand the functioning of complex, terrestrial ecosystems in a rapidly changing planet. We argue that holistic ecosystem models will provide a framework for integrating the many approaches used to study ecosystems, including biodiversity science, population and community ecology, soil science, biogeochemistry, hydrology and climate science. Holistic models will provide new insights into the nature and importance of feedbacks that cut across scales of space and time, and that connect ecosystem domains such as microbes with animals or above with below ground. They will allow us to critically examine the origins and maintenance of ecosystem stability, resilience and sustainability through the lens of systems theory, and provide a much-needed boost for conservation and the management of natural environments. We outline our approach to developing a holistic ecosystem model – the Virtual Ecosystem – and argue that while the construction of such complex models is obviously ambitious, it is both feasible and necessary.

  • Journal article
    Parry C, Turnbull C, Barter L, Gill Ret al., 2024,

    Shedding light on pollination deficits: cueing into plant spectral reflectance signatures to monitor pollination delivery across landscapes

    , Journal of Applied Ecology, Vol: 61, Pages: 2873-2883, ISSN: 0021-8901

    Pollination underlies plant yield, health and reproductive success in agricultural and natural systems worldwide. It is therefore concerning that declining animal pollinator populations compounded by growing demands for food are leading to rising pollination deficits, with globally significant economic and environmental implications.Despite this urgent issue, accurate and scalable tools to quantify and track pollination across useful spatiotemporal scales are lacking. Here, we propose to shed new light on pollination deficits, looking to remote sensing platforms as a transformative mapping and monitoring tool and a solution for pollinator conservation and crop management.Providing a synthesis of our current understanding of pollination-triggered floral senescence and underlying ultrastructural and metabolic changes, we propose how spectral reflectance technologies could be applied to accurately detect pollination events in real-time and at the landscape scale.Synthesis and applications: We highlight where research efforts can be targeted to produce scalable methods for identifying field-relevant bioindicators of pollination. We provide guidance on how spectral imaging accompanied by machine learning and coupled with autonomous operation technologies will enable applications to detect pollination delivery across complex landscapes. Ultimately, such an ecological application will transform our quantitative understanding of pollination services and, by directly linking plant yields and health, will reveal pollination deficits at high resolution to help mitigate risks to food security and ecosystem functioning.

  • Journal article
    Liu Y, Drickamer K, Taylor ME, 2024,

    Preformed mincle dimers stabilized by an interchain disulfide bond in the neck region

    , Glycobiology, Vol: 34, ISSN: 1460-2423

    The sugar-binding receptor mincle stimulates macrophages when it encounters surface glycans on pathogens, such as trehalose dimycolate glycolipid in the outer membrane of mycobacteria. Binding of oligosaccharide ligands to the extracellular C-type carbohydrate-recognition domain (CRD) in mincle initiates intracellular signaling through the common Fc receptor γ (FcRγ) adapter molecule associated with mincle. One potential mechanism for initiation of signaling involves clustering of receptors, so it is important to understand the oligomeric state of mincle. Affinity purification of mincle from transfected mammalian cells has been used to show that mincle exists as a pre-formed, disulfide-linked dimer. Deletion of cysteine residues and chemical crosslinking further demonstrate that the dimers of mincle are stabilized by a disulfide bond between cysteine residues in the neck sequence that links the CRD to the membrane. In contrast, cysteine residues in the transmembrane region of mincle are not required for dimer formation or association with FcRγ. A protocol has been developed for efficient production of a disulfide-linked extracellular domain fragment of mincle in a bacterial expression system by appending synthetic dimerization domains to guide dimer formation in the absence of the membrane anchor.

  • Journal article
    Liu Y, Kim J-W, Feinberg H, Cull N, Weis WI, Taylor ME, Drickamer Ket al., 2024,

    Interactions that define the arrangement of sugar-binding sites in BDCA-2 and dectin-2 dimers

    , Glycobiology, Vol: 34, ISSN: 0959-6658

    The sugar-binding receptors dectin-2 and blood dendritic cell antigen 2 (BDCA-2) bind oligosaccharide ligands through extracellular carbohydrate-recognition domains (CRDs) and initiate intracellular signaling through Fc receptor γ adapters (FcRγ). Dectin-2 stimulates macrophages in response to pathogen binding while BDCA-2 modulates cytokine production in plasmacytoid dendritic cells. The oligomeric states of these receptors and the orientations of their CRDs have been investigated by analysis of a naturally occurring disulfide-bonded variant of BDCA-2 and by replacement of transmembrane domains with N-terminal dimerization domains to create extracellular domain dimers of both dectin-2 and BDCA-2. Analysis of these constructs, as well as previously described crystal structures of the CRDs from these proteins and a novel structure of an extended version of the extracellular domain of dectin-2, showed that there is only limited interaction of the CRDs in the dimers, but interactions can be stabilized by the presence of the neck region. The resulting orientation of sugar-binding sites in the dimers would favor crosslinking of multiple dimers by oligosaccharide ligands, causing clustering of FcRγ to initiate signaling.

  • Journal article
    Peck LD, Llewellyn T, Bennetot B, O'Donnell S, Nowell RW, Ryan MJ, Flood J, Rodríguez de la Vega RC, Ropars J, Giraud T, Spanu PD, Barraclough TGet al., 2024,

    Horizontal transfers between fungal Fusarium species contributed to successive outbreaks of coffee wilt disease.

    , PLoS Biol, Vol: 22

    Outbreaks of fungal diseases have devastated plants and animals throughout history. Over the past century, the repeated emergence of coffee wilt disease caused by the fungal pathogen Fusarium xylarioides severely impacted coffee production across sub-Saharan Africa. To improve the disease management of such pathogens, it is crucial to understand their genetic structure and evolutionary potential. We compared the genomes of 13 historic strains spanning 6 decades and multiple disease outbreaks to investigate population structure and host specialisation. We found that F. xylarioides comprised at least 4 distinct lineages: 1 host-specific to Coffea arabica, 1 to C. canephora var. robusta, and 2 historic lineages isolated from various Coffea species. The presence/absence of large genomic regions across populations, the higher genetic similarities of these regions between species than expected based on genome-wide divergence and their locations in different loci in genomes across populations showed that horizontal transfers of effector genes from members of the F. oxysporum species complex contributed to host specificity. Multiple transfers into F. xylarioides populations matched different parts of the F. oxysporum mobile pathogenicity chromosome and were enriched in effector genes and transposons. Effector genes in this region and other carbohydrate-active enzymes important in the breakdown of plant cell walls were shown by transcriptomics to be highly expressed during infection of C. arabica by the fungal arabica strains. Widespread sharing of specific transposons between F. xylarioides and F. oxysporum, and the correspondence of a putative horizontally transferred regions to a Starship (large mobile element involved in horizontal gene transfers in fungi), reinforce the inference of horizontal transfers and suggest that mobile elements were involved. Our results support the hypothesis that horizontal gene transfers contributed to the repeated emergence of coffee wilt di

  • Journal article
    Stemkovski M, Fife A, Stuart R, Pearse WDet al., 2024,

    Bee Phenological Distributions Predicted by Inferring Vital Rates.

    , Am Nat, Vol: 204, Pages: E115-E127

    AbstractHow bees shift the timing of their seasonal activity (phenology) to track favorable conditions influences the degree to which bee foraging and flowering plant reproduction overlap. While bee phenology is known to shift due to interannual climatic variation and experimental temperature manipulation, the underlying causes of these shifts are poorly understood. Most studies of bee phenology have been phenomenological and have only examined shifts of point estimates, such as first appearance or peak timing. Such cross-sectional measures are convenient for analysis, but foraging activity is distributed across time, and pollination interactions are better described by overlap in phenological abundance curves. Here, we make simultaneous inferences about interannual shifts in bee phenology, emergence and senescence rates, population size, and the effect of floral abundance on observed bee abundance. We do this with a model of transition rates between life stages implemented in a hierarchical Bayesian framework and parameterized with fine-scale abundance time series of the sweat bee Halictus rubicundus at the Rocky Mountain Biological Laboratory in Colorado. We find that H. rubicundus's emergence cueing was highly sensitive to the timing of snowmelt but that emergence rate, senescence rate, and population size did not differ greatly across years. The present approach can be used to glean information about vital rates from other datasets on bee and flower phenology, improving our understanding of pollination interactions.

  • Journal article
    Copland A, Mackie GM, Scarfe L, Jinks E, Lecky DAJ, Gudgeon N, McQuade R, Ono M, Barthel M, Hardt W-D, Ohno H, Hoevenaar WHM, Dimeloe S, Bending D, Maslowski KMet al., 2024,

    Salmonella cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity.

    , EMBO Mol Med, Vol: 16, Pages: 3057-3088

    Bacterial cancer therapy (BCT) is a promising therapeutic for solid tumours. Salmonella enterica Typhimurium (STm) is well-studied amongst bacterial vectors due to advantages in genetic modification and metabolic adaptation. A longstanding paradox is the redundancy of T cells for treatment efficacy; instead, STm BCT depends on innate phagocytes for tumour control. Here, we used distal T cell receptor (TCR) and IFNγ reporter mice (Nr4a3-Tocky-Ifnγ-YFP) and a colorectal cancer (CRC) model to interrogate T cell activity during BCT with attenuated STm. We found that colonic tumour infiltrating lymphocytes (TILs) exhibited a variety of activation defects, including IFN-γ production decoupled from TCR signalling, decreased polyfunctionality and reduced central memory (TCM) formation. Modelling of T-cell-tumour interactions with a tumour organoid platform revealed an intact TCR signalosome, but paralysed metabolic reprogramming due to inhibition of the master metabolic controller, c-Myc. Restoration of c-Myc by deletion of the bacterial asparaginase ansB reinvigorated T cell activation, but at the cost of decreased metabolic control of the tumour by STm. This work shows for the first time that T cells are metabolically defective during BCT, but also that this same phenomenon is inexorably tied to intrinsic tumour suppression by the bacterial vector.

  • Journal article
    Meramveliotakis E, Ortego J, Anastasiou I, Vogler AP, Papadopoulou Aet al., 2024,

    Habitat Association Predicts Population Connectivity and Persistence in Flightless Beetles: A Population Genomics Approach Within a Dynamic Archipelago.

    , Mol Ecol, Vol: 33

    Habitat association has been proposed to affect evolutionary dynamics through its control on dispersal propensity, which is considered a key trait for lineage survival in habitats of low durational stability. The Habitat Constraint hypothesis predicts different micro- and macroevolutionary patterns for stable versus dynamic habitat specialists, but the empirical evidence remains controversial and in insects mostly derives from winged lineages. We here use genome-wide SNP data to assess the effect of habitat association on the population dynamics of two closely related flightless lineages of the genus Eutagenia (Coleoptera: Tenebrionidae), which are co-distributed across the Cyclades islands in the Eastern Mediterranean but are associated with habitat types of different presumed stability: the psammophilous lineage is associated with dynamic sandy coastal habitats, while the geophilous lineage is associated with comparatively stable compact soil habitats. Our comparative population genomic and demographic analyses support higher inter-island gene flow in the psammophilous lineage, presumably due to the physical properties of dynamic sand-dune habitats that promote passive dispersal. We also find consistent bottlenecks in the psammophilous demes, suggesting that lineage evolution in the dynamic habitat is punctuated by local extinction and recolonisation events. The inferred demographic processes are surprisingly uniform among psammophilous demes, but vary considerably among geophilous demes depending on historical island connectivity, indicating more stringent constraints on the dynamic habitat lineage. This study extends the Habitat Constraint hypothesis by demonstrating that selection on dispersal traits is not the only mechanism that can drive consistent differences in evolutionary dynamics between stable versus dynamic habitat specialists.

  • Journal article
    Woubshete M, Chan LI, Diallinas G, Byrne Bet al., 2024,

    The dimer of human SVCT1 is key for transport function.

    , Biochim Biophys Acta Biomembr, Vol: 1866

    Humans and other primates lack the ability to synthesize the essential nutrient, Vitamin C, which is derived exclusively from the diet. Crucial for effective vitamin C uptake are the Na+ dependent Vitamin C transporters, SVCT1 and SVCT2, members of the nucleobase ascorbate transporter (NAT) family. SVCT1 and 2 actively transport the reduced form of Vitamin C, ascorbic acid, into key tissues. The recent structure of the mouse SVCT1 revealed the molecular basis of substrate binding and that, like the other structurally characterised members of the NAT family, it exists as a closely associated dimer. SVCT1 is likely to function via the elevator mechanism with the core domain of each protomer able to bind substrate and move through the membrane carrying the substrate across the membrane. Here we explored the function of a range of variants of the human SVCT1, revealing a range of residues involved in substrate selection and binding, and confirming the importance of the C-terminus in membrane localisation. Furthermore, using a dominant negative mutant we show that the dimer is essential for transport function, as previously seen in the fungal homologue, UapA. In addition, we show that a localisation deficient C-terminal truncation of SVCT1 blocks correct localisation of co-expressed, associated wildtype SVCT1. These results clearly show the importance of the dimer in both correct SVCT1 trafficking and transport activity.

  • Journal article
    Kundu S, Dos Santos Correia G, Lee Y, Ng S, Sykes L, Chan D, Lewis H, Brown R, Kindinger L, Dell A, Feizi T, Haslam S, Liu Y, Marchesi J, MacIntyre D, Bennett Pet al., 2024,

    Secretor status is a modifier of vaginal microbiota-associated preterm birth risk

    , Microbial Genomics, Vol: 10, ISSN: 2057-5858

    Mutations in the FUT2 gene that result in a lack of expression of histo-blood group antigens on secreted glycoproteins may shape the vaginal microbiota with consequences for birth outcome. To test this, we analysed the relationship between secretor status, vaginal microbiota and gestational length in an ethnically diverse cohort of 302 pregnant women, including 82 who delivered preterm. Lactobacillus gasseri and L. jensenii were found to have distinct co-occurrence patterns with other microbial taxa in non-secretors. Moreover, non-secretors with Lactobacillus spp. depleted high diversity vaginal microbiota in early pregnancy had significantly shorter gestational length than Lactobacillus spp. dominated non-secretors (mean of 241.54 days (sd=47.14) versus 266.21 (23.61); P-value=0.0251). Similar gestational length differences were observed between non-secretors with high vaginal diversity and secretors with Lactobacillus spp. dominance (mean of 262.52 days (SD=27.73); p-value=0.0439) or depletion (mean of 266.05 days (SD=20.81); p-value=0.0312). Our data highlight secretor status and blood-group antigen expression as being important mediators of vaginal microbiota–host interactions in the context of preterm birth risk.

  • Journal article
    Ono M, Crompton T, 2024,

    A multidimensional toolkit for elucidating temporal trajectories in cell development in vivo.

    , Development

    Progenitor cells initiate development upon receiving key signals, dynamically altering gene and protein expression to diverge into various lineages and fates. Despite the use of several experimental approaches, including the Fluorescent Timer-based method Timer-of-cell-kinetics-and-activity (Tocky), analysing time-dependent processes at the single-cell level in vivo remains challenging. This study introduces a novel integrated experimental and computational approach, using an advanced multidimensional toolkit. This toolkit facilitates the simultaneous examination of temporal progression and T-cell profiles using high-dimensional flow cytometric data. Employing novel algorithms based on Canonical Correspondence Analysis (CCA) and network analysis, our toolkit identifies developmental trajectories and analyses dynamic changes in developing cells. The efficacy of this approach is demonstrated through analysing thymic T-cells from Nr4a3-Tocky mice, which monitor activities downstream of the T-cell receptor (TCR) signal. Further validation was achieved by deleting the proapoptotic gene Bcl2l11 (Bim) in Nr4a3-Tocky mice. This revealed dynamic changes in thymic T-cells during cellular development and negative selection following TCR signalling. Overall, this study establishes a new method for analysing the temporal dynamics of individual developing cells in response to in vivo signalling cues.

  • Journal article
    Kriezis A, Vitale M, Morselli G, Crisanti A, Bernardini Fet al., 2024,

    Unravelling the role of mitochondrial DNA in hybrid incompatibility within species of the Anopheles gambiae complex.

    , Sci Rep, Vol: 14

    Isolation mechanisms between mosquito species of the Anopheles gambiae complex, which includes major malaria vectors, remain poorly understood. In some cases, pre-zygotic barriers have been shown to limit gene flow between species of the complex, leading to a low level of hybridisation in nature. Post-zygotic mechanisms manifest with F1 hybrid males fully sterile and F1 hybrid females with reduced fertility. Genetic approaches combined with DNA sequencing techniques have highlighted the involvement of genomic regions in hybrid incompatibility with a predominant role of the X chromosome. In addition, differences in the phenotype of F1 hybrid males have been identified depending on the directionality of the parental cross used to generate them. All these studies have focused on the interaction of nuclear DNA elements in hybrid individuals. Given the role that mitochondrial DNA plays in genetic incompatibilities within other organisms and its unique inheritance pattern, commonly maternal, we conducted a genetic study that relied on the introgression of mitochondrial DNA between Anopheles gambiae and Anopheles arabiensis. The findings indicate that the mitochondrial switch does not appear to restore the fertility of F1 hybrid males, suggesting that mitochondrial DNA may not play a role in hybrid incompatibilities in these Anopheles species.

  • Journal article
    Liu K, Grover M, Trusch F, Vagena-Pantoula C, Ippolito D, Barkoulas Met al., 2024,

    Paired C-type lectin receptors mediate specific recognition of divergent oomycete pathogens in C. elegans

    , Cell Reports, Vol: 43, ISSN: 2211-1247

    Innate immune responses can be triggered upon detection of pathogen- or damage-associated molecular patterns by host receptors that are often present on the surface of immune cells. While invertebrates like Caenorhabditis elegans lack professional immune cells, they still mount pathogen-specific responses. However, the identity of host receptors in the nematode remains poorly understood. Here, we show that C-type lectin receptors mediate species-specific recognition of divergent oomycetes in C. elegans. A CLEC-27/CLEC-35 pair is essential for recognition of the oomycete Myzocytiopsis humicola, while a CLEC-26/CLEC-36 pair is required for detection of Haptoglossa zoospora. Both clec pairs are transcriptionally regulated through a shared promoter by the conserved PRD-like homeodomain transcription factor CEH-37/OTX2 and act in sensory neurons and the anterior intestine to trigger a protective immune response in the epidermis. This system enables redundant tissue sensing of oomycete threats through canonical CLEC receptors and host defense via cross-tissue communication.

  • Journal article
    Waring BG, Lancastle L, Bell T, Bidartondo MI, García-Díaz P, Lambin X, Vanguelova E, Windram FAet al., 2024,

    Windthrow disturbance impacts soil biogeochemistry and bacterial communities in a temperate forest

    , Plant and Soil: international journal on plant-soil relationships, ISSN: 0032-079X

    AimsForests across the world are subject to disturbance via wind, wildfire, and pest and disease outbreaks. Yet we still have an incomplete understanding of how these stressors impact forest biota—particularly the soil microbes, which govern forest carbon and nutrient cycling.MethodsHere, we investigated the impact of a severe windstorm on soil bacterial communities in Kielder Forest, a temperate coniferous forest in the north of England. Within ten individual sites, defined by common stand composition and topography, we established 50 m2 plots in undisturbed stands, and in nearby stands that were moderately and/or severely disturbed by windthrow. Soils were sampled within each of the 22 study plots, and analysed for changes in carbon and nitrogen content, pH, root biomass, and bacterial community structure. We separately sequenced bacteria from bulk soils, rhizosphere soils, and root tissues to assess whether disturbance impacts varied based on the proximity of microbiota to tree roots.ResultsLess than a year after the storm, we found that the most severely disturbed stands had lower canopy cover, lower soil carbon content, higher soil pH, and a smaller fine root biomass than the undisturbed stands. Disturbance also impacted bacterial community beta-diversity, but the effects were subtle and did not vary among assemblages in bulk vs. rhizosphere soils.ConclusionsImpacts of aboveground disturbance on soil biogeochemistry can be significant, but soil bacterial communities are relatively well-buffered against these changes. However, altered patterns of root growth and carbon cycling may have longer-term implications for forest recovery after windthrow disturbances.

  • Journal article
    Clegg T, Pawar S, 2024,

    Variation in thermal physiology can drive the temperature-dependence of microbial community richness

    , eLife, ISSN: 2050-084X

    Predicting how species diversity changes along environmental gradients is an enduring problem in ecology. In microbes current theories tend to invoke energy availability and enzyme kinetics as the main drivers of temperature-richness relationships. Here we derive a general empirically-grounded theory that can explain this phenomenon by linking microbial species richness in competitive communities to variation in the temperature-dependence of their interaction and growth rates. Specifically, the shape of the microbial community temperature-richness relationship depends on how rapidly the strength of effective competition between species pairs changes with temperature relative to the variance of their growth rates. Furthermore, it predicts that a thermal specialist-generalist tradeoff in growth rates alters coexistence by shifting this balance, causing richness to peak at relatively higher temperatures. Finally, we show that the observed patterns of variation in thermal performance curves of metabolic traits across extant bacterial taxa is indeed sufficient to generate the variety of community-level temperature-richness responses observed in the real world. Our results provide a new and general mechanism that can help explain temperature-diversity gradients in microbial communities, and provide a quantitative framework for interlinking variation in the thermal physiology of microbial species to their community-level diversity.

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