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Thesis dissertationIrakleidi DA, 2024,
The Rtc RNA Repair System in E. coli: underlying molecular regulation and its role in infection and antibiotic resistance.
The Rtc RNA repair system, comprising of the RNA cyclase RtcA, the RNA ligase RtcB and the transcriptional activator RtcR, is present in many bacterial species causing human diseases, including the model organisms and putative pathogens Escherichia coli and Salmonella enterica, and has been suggested to play a role in the development of antibiotic resistance. Here we explore the events underlying Rtc activation via RtcR and its CRISPR-associated Rossmann fold (CARF) domain as well as its physiological role during infection. In vitro transcription and ATPase assays showcased the inherent inhibition exerted by the RtcR CARF domain towards RtcR activation as well as its recognition of 2’,3’cP RNA termini – known to act as substrates for the system’s ligase, RtcB – as inducing ligands. End-labelling as well as adapter ligation with RtcB of in vivo bound RNA extracts derived from wildtype or N-terminal truncated RtcR provides evidence for the in vivo association of 2’,3’cP-RNA molecules with RtcR. Β-galactosidase assays demonstrated more prominent rtcBA expression in the rtc-inducing ΔhisT and Δrna E. coli mutants when compared to the wildtype, regardless of nutrient abundance. rtcBA expression appears at least partly RtcR-dependent, relying on certain inverted repeats, possibly carrying RtcR binding sites, located at specific positions in the rtcBA promoter. Pathogenicity assays using the infection model G. mellonella demonstrated that wildtype E. coli K12 MG1655 cells are more virulent in vivo compared to variants lacking any of the Rtc components or the functionally important RtcR CARF domain. Complementation of rtc gene deletions with wildtype Rtc proteins, but not functionally catalytic mutants, reverses the infection phenotype to that of wildtype. Post-infection treatment of larvae with the ribosome-targeting antibiotics chloramphenicol and tetracycline fails at affecting the survival rates of larvae infect
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Journal articleThorpe P, Altmann S, Lopez-Cobollo R, et al., 2024,
Multi-omics approaches define novel aphid effector candidates associated with virulence and avirulence phenotypes
, BMC Genomics, Vol: 25, ISSN: 1471-2164BackgroundCompatibility between plant parasites and their hosts is genetically determined {Citation}both interacting organisms. For example, plants may carry resistance (R) genes or deploy chemical defences. Aphid saliva contains many proteins that are secreted into host tissues. Subsets of these proteins are predicted to act as effectors, either subverting or triggering host immunity. However, associating particular effectors with virulence or avirulence outcomes presents challenges due to the combinatorial complexity. Here we use defined aphid and host genetics to test for co-segregation of expressed aphid transcripts and proteins with virulent or avirulent phenotypes.ResultsWe compared virulent and avirulent pea aphid parental genotypes, and their bulk segregant F1 progeny on Medicago truncatula genotypes carrying or lacking the RAP1 (Resistance to Acyrthosiphon pisum 1) resistance quantitative trait locus. Differential gene expression analysis of whole body and head samples, in combination with proteomics of saliva and salivary glands, enabled us to pinpoint proteins associated with virulence or avirulence phenotypes. There was relatively little impact of host genotype, whereas large numbers of transcripts and proteins were differentially expressed between parental aphids, likely a reflection of their classification as divergent biotypes within the pea aphid species complex. Many fewer transcripts intersected with the equivalent differential expression patterns in the bulked F1 progeny, providing an effective filter for removing genomic background effects. Overall, there were more upregulated genes detected in the F1 avirulent dataset compared with the virulent one. Some genes were differentially expressed both in the transcriptome and in the proteome datasets, with aminopeptidase N proteins being the most frequent differentially expressed family. In addition, a substantial proportion (27%) of salivary proteins lack annotations, suggesting that many novel functi
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Journal articleLázaro IA, Anastasaki A, Ardoña HAM, et al., 2024,
35 challenges in materials science being tackled by PIs under 35(ish) in 2024
, Matter, Vol: 7, Pages: 3699-3706, ISSN: 2590-2385Here, we highlight 35 global researchers approximately under the age of 35. This third annual cohort was self-generated by initial seed invitations sent by the editorial team, with each contributor suggesting two more in a nominally supervised self-selecting pyramid-like scheme. The final collection reflects both the diversity and excitement across the field of materials science.
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Journal articleZhang-Zheng H, Deng X, Aguirre-Gutierrez J, et al., 2024,
Why models underestimate West African tropical forest primary productivity
, Nature Communications, Vol: 15, ISSN: 2041-1723Tropical forests dominate terrestrial photosynthesis, yet there are major contradictions in our understanding due to a lack of field studies, especially outside the tropical Americas. A recent field study indicated that West African forests have among the highest forests gross primary productivity (GPP) yet observed, contradicting models that rank them lower than Amazonian forests. Here, we show possible reasons for this data-model mismatch. We found that biometric GPP measurements are on average 56.3% higher than multiple global GPP products at the study sites. The underestimation of GPP largely disappears when a standard photosynthesis model is informed by local field-measured values of (a) fractional absorbed photosynthetic radiation (fAPAR), and (b) photosynthetic traits. Remote sensing products systematically underestimate fAPAR (33.9% on average at study sites) due to cloud contamination issues. The study highlights the potential widespread underestimation of tropical forests GPP and carbon cycling and hints at the ways forward for model and input data improvement.
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Conference paperMillar J, Sethi S, Haddadi H, et al., 2024,
Poster: Towards Low-Power Comprehensive Biodiversity Monitoring
, Pages: 844-846The Kunming-Montreal Global Biodiversity Framework sets ambitious targets for 2023, including halting human-induced species extinction. Achieving these requires comprehensive data on global biodiversity patterns, which can only be gathered through in-situ distributed sensor networks. However, these multi-device networks are constrained by battery lifetimes, must gather rich data from power-hungry sensors, and yet need to be deployed in remote environments for long periods. This note introduces a prototype multi-sensor device, and outlines how embedded scheduling could be used for extending sensor lifetime and resource-efficiency.
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Journal articleLiu Y, Chen JM, Xu M, et al., 2024,
Improved global estimation of seasonal variations in C3 photosynthetic capacity based on eco-evolutionary optimality hypotheses and remote sensing
, REMOTE SENSING OF ENVIRONMENT, Vol: 313, ISSN: 0034-4257 -
Journal articleSelles J, Alric J, Rutherford AW, et al., 2024,
In vivo ElectroChromic Shift measurements of photosynthetic activity in far-red absorbing cyanobacteria
, BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, Vol: 1865, ISSN: 0005-2728 -
Journal articleBenjamin S, Jégouzo S, Lieng C, et al., 2024,
A human lectin array for characterizing host-pathogen interactions
, Journal of Biological Chemistry, Vol: 300, ISSN: 0021-9258A human lectin array has been developed to probe the interactions of innate immune receptors with pathogenic and commensal micro-organisms. Following the successful introduction of a lectin array containing all of the cow C-type carbohydrate-recognition domains (CRDs), a human array described here contains the C-type CRDs as well as CRDs from other classes of sugar-binding receptors, including galectins, siglecs, R-type CRDs, ficolins, intelectins and chitinase-like lectins. The array is constructed with CRDs modified with single-site biotin tags, ensuring that the sugar-binding sites in CRDs are displayed on a streptavidin-coated surface in a defined orientation and are accessible to the surfaces of microbes. A common approach used for expression and display of CRDs from all of the different structural categories of glycan-binding receptors allows comparisons across lectin families. In addition to previously documented protocols for binding of fluorescently-labeled bacteria, methods have been developed for detecting unlabeled bacteria bound to the array by counter-staining with DNA binding dye. Screening has also been undertaken with viral glycoproteins and bacterial and fungal polysaccharides. The array provides an unbiased screen for sugar ligands that interact with receptors and many show binding not anticipated from earlier studies. For example, some of the galectins bind with high affinity to bacterial glycans that lack lactose or N acetyllactosamine. The results demonstrate the utility of the human lectin array for providing a unique overview of the interactions of multiple classes of glycan-binding proteins in the innate immune system with different types of micro-organisms.
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Journal articlePrentice IC, Balzarolo M, Bloomfield KJ, et al., 2024,
Principles for satellite monitoring of vegetation carbon uptake
, Nature Reviews Earth & Environment, Vol: 5, ISSN: 2662-138XRemote sensing-based numerical models harness satellite-borne measurements of light absorption by vegetation to estimate global patterns and trends in gross primary production (GPP)—the basis of the terrestrial carbon cycle. In this Perspective, we discuss the challenges in estimating GPP using these models and explore ways to improve their reliability. Current models vary substantially in their structure and produce differing results, especially as regards temporal trends in GPP. Many models invoke the light use efficiency (LUE) principle, which links light absorption to photosynthesis and plant biomass production, to estimate GPP. But these models vary in their assumptions about the controls of LUE and typically depend on many, poorly known parameters. Eco-evolutionary optimality principles can greatly reduce parameter requirements, and can improve the accuracy and consistency of GPP estimates and interpretations of their relationships with environmental drivers. Integrating data across different satellites and sensors, and utilising auxiliary optical band retrievals, could enhance spatiotemporal resolution and improve models' ability to detect aspects of vegetation physiology, including drought stress. Extending and harmonizing the eddy-covariance flux tower network will support systematic evaluation of GPP models. Enhancing the reliability of GPP and biomass production estimates will better characterise temporal variation and improve understanding of the terrestrial carbon cycle’s response to environmental change.
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Journal articleEwers RM, 2024,
An audacious approach to conservation
, TRENDS IN ECOLOGY & EVOLUTION, Vol: 39, Pages: 995-1003, ISSN: 0169-5347 -
Journal articleQi M, Suz LM, Bidartondo MI, et al., 2024,
Fruitbody and root data infer different environmental niches for ectomycorrhizal fungi
, JOURNAL OF BIOGEOGRAPHY, Vol: 51, Pages: 2221-2236, ISSN: 0305-0270 -
Journal articleWilliams J, Pettorelli N, Dowell R, et al., 2024,
SimpleMetaPipeline: Breaking the bioinformatics bottleneck in metabarcoding
, METHODS IN ECOLOGY AND EVOLUTION, Vol: 15, Pages: 1949-1957, ISSN: 2041-210X -
Journal articleOikawa K, Fujisaki K, Shimizu M, et al., 2024,
The blast pathogen effector AVR-Pik binds and stabilizes rice heavy metal-associated (HMA) proteins to co-opt their function in immunity
, PLOS PATHOGENS, Vol: 20, ISSN: 1553-7366 -
Journal articleMadhuprakash J, Toghani A, Contreras MP, et al., 2024,
A disease resistance protein triggers oligomerization of its NLR helper into a hexameric resistosome to mediate innate immunity
, Science Advances, Vol: 10, ISSN: 2375-2548NRCs are essential helper NLR (nucleotide-binding domain and leucine-rich repeat) proteins that execute immune responses triggered by sensor NLRs. The resting state of NbNRC2 was recently shown to be a homodimer, but the sensor-activated state remains unclear. Using cryo-EM, we determined the structure of sensor-activated NbNRC2, which forms a hexameric inflammasome-like resistosome. Mutagenesis of the oligomerization interface abolished immune signaling, confirming the functional significance of the NbNRC2 resistosome. Comparative structural analyses between the resting state homodimer and sensor-activated homohexamer revealed substantial rearrangements, providing insights into NLR activation mechanisms. Furthermore, structural comparisons between NbNRC2 hexamer and previously reported CC-NLR pentameric assemblies revealed features allowing an additional protomer integration. Using the NbNRC2 hexamer structure, we assessed the recently released AlphaFold 3 for predicting activated CC-NLR oligomers, revealing high-confidence modeling of NbNRC2 and other CC-NLR amino-terminal α1 helices, a region proven difficult to resolve structurally. Overall, our work sheds light on NLR activation mechanisms and expands understanding of NLR structural diversity.
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Journal articleBarber RA, Yang J, Yang C, et al., 2024,
Climate and ecology predict latitudinal trends in sexual selection inferred from avian mating systems
, PLOS BIOLOGY, Vol: 22, ISSN: 1544-9173 -
Journal articleWilliams J, Newbold T, Millard J, et al., 2024,
Important Crop Pollinators Respond Less Negatively to Anthropogenic Land Use Than Other Animals
, Ecology and Evolution, ISSN: 2045-7758Animal-mediated pollination is a key ecosystem service required to some extent by almost three-quarters of the leading human food crops in global food production. Anthropogenic pressures such as habitat loss and land-use intensification are causing shifts in ecological community composition, potentially resulting in declines in pollination services and impacting crop production. Previous research has often overlooked interspecific differences in pollination contribution, yet such differences mean that biodiversity declines will not necessarily negatively impact pollination. Here, we use a novel species-level ecosystem service contribution matrix along with mixed-effects models to explore how groups of terrestrial species who contribute differently to crop pollination respond globally to land-use type, land-use intensity, and availability of natural habitats in the surrounding landscape. We find that the species whose contribution to crop pollination is higher generally respond less negatively (and in some cases positively) to human disturbance of land, compared to species that contribute less or not at all to pollination. This result may be due to these high-contribution species being less sensitive to anthropogenic land conversions, which has led humans to being more reliant on them for crop pollination. However, it also suggests that there is potential for crop pollination to be resilient in the face of anthropogenic land conversions. With such a high proportion of food crops requiring animal-mediated pollination to some extent, understanding how anthropogenic landscapes impact ecological communities and the consequences for pollination is critical for ensuring food security.
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Journal articleCheong B, Tang W, Kostrzewa M, et al., 2024,
Use of stable isotope combined with intact cell lipidomic by routine MALDI mass spectrometry analysis for rapid drug susceptibility assay in mycobacteria
, RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Vol: 38, ISSN: 0951-4198 -
Journal articleSchroeder J, Dunning J, Chan AHH, et al., 2024,
Not so social in old age: demography as one driver of decreasing sociality
, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 379, ISSN: 0962-8436 -
Conference paperRuotolo I, Saglietto A, Saturi G, et al., 2024,
Artificial intelligence (AI)-enhanced electrocardiography: a machine-learning model for differential diagnosis between hypertrophic cardiomyopathy, cardiac amyloidosis and Anderson-Fabry disease
, European-Society-of-Cardiology Congress (ESC), Publisher: OXFORD UNIV PRESS, ISSN: 0195-668X -
Conference paperDi Nicola F, Barile L, Schiavo MA, et al., 2024,
Anderson-Fabry disease patients with anatomical heart hypertrophy express a higher degree of electrocardiographic hypertrophy compared to hypertrophic cardiomyopathy patients
, European-Society-of-Cardiology Congress (ESC), Publisher: OXFORD UNIV PRESS, ISSN: 0195-668X -
Journal articleSelvaraj M, Toghani A, Pai H, et al., 2024,
Activation of plant immunity through conversion of a helper NLR homodimer into a resistosome
, PLoS Biology, Vol: 22, ISSN: 1544-9173Nucleotide-binding domain and leucine-rich repeat (NLR) proteins can engage in complex interactions to detect pathogens and execute a robust immune response via downstream helper NLRs. However, the biochemical mechanisms of helper NLR activation by upstream sensor NLRs remain poorly understood. Here, we show that the coiled-coil helper NLR NRC2 from Nicotiana benthamiana accumulates in vivo as a homodimer that converts into a higher-order oligomer upon activation by its upstream virus disease resistance protein Rx. The cryo-EM structure of NbNRC2 in its resting state revealed intermolecular interactions that mediate homodimer formation and contribute to immune receptor autoinhibition. These dimerization interfaces have diverged between paralogous NRC proteins to insulate critical network nodes and enable redundant immune pathways, possibly to minimise undesired cross-activation and evade pathogen suppression of immunity. Our results expand the molecular mechanisms of NLR activation pointing to transition from homodimers to higher-order oligomeric resistosomes.
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Journal articleHancock PA, North A, Leach AW, et al., 2024,
The potential of gene drives in malaria vector species to control malaria in African environments
, NATURE COMMUNICATIONS, Vol: 15 -
Journal articleKontopoulos D-G, Sentis A, Daufresne M, et al., 2024,
No universal mathematical model for thermal performance curves across traits and taxonomic groups
, Nature Communications, Vol: 15, ISSN: 2041-1723In ectotherms, the performance of physiological, ecological and life-history traits universally increases with temperature to a maximum before decreasing again. Identifying the most appropriate thermal performance model for a specific trait type has broad applications, from metabolic modelling at the cellular level to forecasting the effects of climate change on population, ecosystem and disease transmission dynamics. To date, numerous mathematical models have been designed, but a thorough comparison among them is lacking. In particular, we do not know if certain models consistently outperform others and how factors such as sampling resolution and trait or organismal identity influence model performance. To fill this knowledge gap, we compile 2,739 thermal performance datasets from diverse traits and taxa, to which we fit a comprehensive set of 83 existing mathematical models. We detect remarkable variation in model performance that is not primarily driven by sampling resolution, trait type, or taxonomic information. Our results reveal a surprising lack of well-defined scenarios in which certain models are more appropriate than others. To aid researchers in selecting the appropriate set of models for any given dataset or research objective, we derive a classification of the 83 models based on the average similarity of their fits.
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Journal articleMasignani V, Rappuoli R, Pizza M, 2024,
Next generation of "magic bullets", solutions from the microbial pangenome
, EMBO MOLECULAR MEDICINE, Vol: 16, Pages: 2271-2273, ISSN: 1757-4676 -
Journal articleGaboriau T, Tobias JA, Silvestro D, et al., 2024,
Exploring the Macroevolutionary Signature of Asymmetric Inheritance at Speciation
, SYSTEMATIC BIOLOGY, ISSN: 1063-5157 -
Journal articlePalmer J, Samuelson AE, Gill RJ, et al., 2024,
Foraging distance distributions reveal how honeybee waggle dance recruitment varies with landscape
, Communications Biology, Vol: 7, ISSN: 2399-3642Honeybee (Apis mellifera) colonies use a unique collective foraging system, the waggle dance, to communicate and process the location of resources. Here, we present a means to quantify the effect of recruitment on colony forager allocation across the landscape by simply observing the waggle dance on the dancefloor. We show first, through a theoretical model, that recruitment leaves a characteristic imprint on the distance distribution of foraging sites that a colony visits, which varies according to the proportion of trips driven by individual search. Next, we fit this model to the real-world empirical distance distribution of forage sites visited by 20 honeybee colonies in urban and rural landscapes across South East England, obtained via dance decoding. We show that there is considerable variation in the use of dancing information in colony foraging, particularly in agri-rural landscapes. In our dataset, reliance on dancing increases as arable land gives way to built-up areas, suggesting that dancing may have the greatest impact on colony foraging in the complex and heterogeneous landscapes of forage-rich urban areas. Our model provides a tool to assess the relevance of this extraordinary behaviour across modern anthropogenic landscape types.
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Journal articleJaramillo V, Hebron H, Wong S, et 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, ISSN: 0161-8105 -
Journal articleDrobnič T, Cohen EJ, Calcraft T, et al., 2024,
Molecular model of a bacterial flagellar motor in situ reveals a "parts-list" of protein adaptations to increase torque.
, bioRxivOne hurdle to understanding how molecular machines work, and how they evolve, is our inability to see their structures in situ. Here we describe a minicell system that enables in situ cryogenic electron microscopy imaging and single particle analysis to investigate the structure of an iconic molecular machine, the bacterial flagellar motor, which spins a helical propeller for propulsion. We determine the structure of the high-torque Campylobacter jejuni motor in situ, including the subnanometre-resolution structure of the periplasmic scaffold, an adaptation essential to high torque. Our structure enables identification of new proteins, and interpretation with molecular models highlights origins of new components, reveals modifications of the conserved motor core, and explain how these structures both template a wider ring of motor proteins, and buttress the motor during swimming reversals. We also acquire insights into universal principles of flagellar torque generation. This approach is broadly applicable to other membrane-residing bacterial molecular machines complexes.
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Journal articleMatthews TJ, Triantis KA, Wayman JP, et al., 2024,
The global loss of avian functional and phylogenetic diversity from anthropogenic extinctions.
, Science, Vol: 386, Pages: 55-60Humans have been driving a global erosion of species richness for millennia, but the consequences of past extinctions for other dimensions of biodiversity-functional and phylogenetic diversity-are poorly understood. In this work, we show that, since the Late Pleistocene, the extinction of 610 bird species has caused a disproportionate loss of the global avian functional space along with ~3 billion years of unique evolutionary history. For island endemics, proportional losses have been even greater. Projected future extinctions of more than 1000 species over the next two centuries will incur further substantial reductions in functional and phylogenetic diversity. These results highlight the severe consequences of the ongoing biodiversity crisis and the urgent need to identify the ecological functions being lost through extinction.
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Journal articleBarnada SM, de Gracia AG, Morenilla-Palao C, et al., 2024,
ARID1A-BAF coordinates ZIC2 genomic occupancy for epithelial-to-mesenchymal transition in cranial neural crest specification
, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 111, ISSN: 0002-9297
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