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  • Journal article
    Larrouy-Maumus G, Dortet L, Nix ID, Maier T, Oberheitmann B, Sparbier K, Kostrzewa Met al., 2023,

    Two-site study on performances of a commercially available MALDI-TOF MS-based assay for the detection of colistin resistance in Escherichia coli

    , European Journal of Clinical Microbiology and Infectious Diseases: an international journal on pathogenesis, diagnosis, epidemiology, therapy, and prevention of infectious diseases, Vol: 42, Pages: 669-679, ISSN: 0934-9723

    Colistin is a last resort drug for the treatment of multiple drug-resistant (MDR) Gram-negative bacterial infections. Rapid methods to detect resistance are highly desirable. Here, we evaluated the performance of a commercially available MALDI-TOF MS-based assay for colistin resistance testing in Escherichia coli at two different sites. Ninety clinical E. coli isolates were provided by France and tested in Germany and UK using a MALDI-TOF MS-based colistin resistance assay. Lipid A molecules of the bacterial cell membrane were extracted using the MBT Lipid Xtract Kit™ (RUO; Bruker Daltonics, Germany). Spectra acquisition and evaluation were performed by the MBT HT LipidART Module of MBT Compass HT (RUO; Bruker Daltonics) on a MALDI Biotyper® sirius system (Bruker Daltonics) in negative ion mode. Phenotypic colistin resistance was determined by broth microdilution (MICRONAUT MIC-Strip Colistin, Bruker Daltonics) and used as a reference. Comparing the results of the MALDI-TOF MS-based colistin resistance assay with the data of the phenotypic reference method for the UK, sensitivity and specificity for the detection of colistin resistance were 97.1% (33/34) and 96.4% (53/55), respectively. Germany showed 97.1% (33/34) sensitivity and 100% (55/55) specificity for the detection of colistin resistance by MALDI-TOF MS. Applying the MBT Lipid Xtract™ Kit in combination with MALDI-TOF MS and dedicated software showed excellent performances for E. coli. Analytical and clinical validation studies must be performed to demonstrate the performance of the method as a diagnostic tool.

  • Journal article
    Wisden W, Franks NP, 2023,

    Biochemical pathways of sleep

    , CELL RESEARCH, Vol: 33, Pages: 417-418, ISSN: 1001-0602
  • Journal article
    Kavil S, Laverick A, Whitfield CJ, Banks AM, Howard TPet al., 2023,

    Methods for embedding cell-free protein synthesis reactions in macro-scale hydrogels

    , Journal of Visualized Experiments, Pages: 1-14, ISSN: 1940-087X

    Synthetic gene networks provide a platform for scientists and engineers to design and build novel systems with functionality encoded at a genetic level. While the dominant paradigm for the deployment of gene networks is within a cellular chassis, synthetic gene networks may also be deployed in cell-free environments. Promising applications of cell-free gene networks include biosensors, as these devices have been demonstrated against biotic (Ebola, Zika, and SARS-CoV-2 viruses) and abiotic (heavy metals, sulfides, pesticides, and other organic contaminants) targets. Cell-free systems are typically deployed in liquid form within a reaction vessel. Being able to embed such reactions in a physical matrix, however, may facilitate their broader application in a wider set of environments. To this end, methods for embedding cell-free protein synthesis (CFPS) reactions in a variety of hydrogel matrices have been developed. One of the key properties of hydrogels conducive to this work is the high-water reconstitution capacity of hydrogel materials. Additionally, hydrogels possess physical and chemical characteristics that are functionally beneficial. Hydrogels can be freeze-dried for storage and rehydrated for use later. Two step-by-step protocols for the inclusion and assay of CFPS reactions in hydrogels are presented. First, a CFPS system can be incorporated into a hydrogel via rehydration with a cell lysate. The system within the hydrogel can then be induced or expressed constitutively for complete protein expression through the hydrogel. Second, cell lysate can be introduced to a hydrogel at the point of polymerization, and the entire system can be freeze-dried and rehydrated at a later point with an aqueous solution containing the inducer for the expression system encoded within the hydrogel. These methods have the potential to allow for cell-free gene networks that confer sensory capabilities to hydrogel materials, with the potential for deployment beyond the laboratory

  • Journal article
    Agirre J, Atanasova M, Bagdonas H, Ballard CB, Basle A, Beilsten-Edmands J, Borges RJ, Brown DG, Burgos-Marmol JJ, Berrisford JM, Bond PS, Caballero I, Catapano L, Chojnowski G, Cook AG, Cowtan KD, Croll TI, Debreczeni JE, Devenish NE, Dodson EJ, Drevon TR, Emsley P, Evans G, Evans PR, Fando M, Foadi J, Fuentes-Montero L, Garman EF, Gerstel M, Gildea RJ, Hatti K, Hekkelman ML, Heuser P, Hoh SW, Hough MA, Jenkins HT, Jimenez E, Joosten RP, Keegan RM, Keep N, Krissinel EB, Kolenko P, Kovalevskiy O, Lamzin VS, Lawson DM, Lebedev AA, Leslie AGW, Lohkamp B, Long F, Maly M, McCoy AJ, McNicholas SJ, Medina A, Millan C, Murray JW, Murshudov GN, Nicholls RA, Noble MEM, Oeffner R, Pannu NS, Parkhurst JM, Pearce N, Pereira J, Perrakis A, Powell HR, Read RJ, Rigden DJ, Rochira W, Sammito M, Rodriguez FS, Sheldrick GM, Shelley KL, Simkovic F, Simpkin AJ, Skubak P, Sobolev E, Steiner RA, Stevenson K, Tews I, Thomas JMH, Thorn A, Trivino Valls J, Uski V, Uson I, Vagin A, Velankar S, Vollmar M, Walden H, Waterman D, Wilson KS, Winn MD, Winter G, Wojdyr M, Yamashita Ket al., 2023,

    The CCP4 suite: integrative software for macromolecular crystallography

    , Acta Crystallographica Section D: Structural Biology, Vol: 79, Pages: 449-461, ISSN: 2059-7983

    The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.

  • Journal article
    Kenna D, Graystock P, Gill R, 2023,

    Toxic temperatures: bee behaviours exhibit divergent pesticide toxicity relationships with warming

    , Global Change Biology, Vol: 29, Pages: 2981-2998, ISSN: 1354-1013

    Climate change and agricultural intensification are exposing insect pollinators to temperature extremes and increasing pesticide usage. Yet, we lack good quantification of how temperature modulates the sublethal effects of pesticides on behaviours vital for fitness and pollination performance. Consequently, we are uncertain if warming decreases or increases the severity of different pesticide impacts, and whether separate behaviours vary in the direction of response. Quantifying these interactive effects is vital in forecasting pesticide risk across climate regions and informing pesticide application strategies and pollinator conservation. This multi-stressor study investigated the responses of six functional behaviours of bumblebees when exposed to either a neonicotinoid (imidacloprid) or a sulfoximine (sulfoxaflor) across a standardised low, mid, and high temperature. We found the neonicotinoid had a significant effect on five of the six behaviours, with a greater effect at the lower temperature(s) when measuring responsiveness, the likelihood of movement, walking rate, and food consumption rate. In contrast, the neonicotinoid had a greater impact on flight distance at the higher temperature. Our findings show that different organismal functions can exhibit divergent thermal responses, with some pesticide-affected behaviours showing greater impact as temperatures dropped, and others as temperatures rose. We must therefore account for environmental context when determining pesticide risk. Moreover, we found evidence of synergistic effects, with just a 3°C increase causing a sudden drop in flight performance, despite seeing no effect of pesticide at the two lower temperatures. Our findings highlight the importance of multi-stressor studies to quantify threats to insects, which will help to improve dynamic evaluations of population tipping points and spatiotemporal risks to biodiversity across different climate regions.

  • Journal article
    Weeks TL, Betts MG, Pfeifer M, Wolf C, Banks-Leite C, Barbaro L, Barlow J, Cerezo A, Kennedy CM, Kormann UG, Marsh CJ, Olivier PI, Phalan BT, Possingham HP, Wood EM, Tobias JAet al., 2023,

    Climate-driven variation in dispersal ability predicts responses to forest fragmentation in birds

    , Nature Ecology and Evolution, Vol: 7, Pages: 1079-1091, ISSN: 2397-334X

    Species sensitivity to forest fragmentation varies latitudinally, peaking in the tropics. A prominent explanation for this pattern is that historical landscape disturbance at higher latitudes has removed fragmentation-sensitive species or promoted the evolution of more resilient survivors. However, it is unclear whether this so-called extinction filter is the dominant driver of geographic variation in fragmentation sensitivity, particularly because climatic factors may also cause latitudinal gradients in dispersal ability, a key trait mediating sensitivity to habitat fragmentation. Here we combine field survey data with a morphological proxy for avian dispersal ability (hand-wing index) to assess responses to forest fragmentation in 1,034 bird species worldwide. We find that fragmentation sensitivity is strongly predicted by dispersal limitation and that other factors—latitude, body mass and historical disturbance events—have relatively limited explanatory power after accounting for species differences in dispersal. We also show that variation in dispersal ability is only weakly predicted by historical disturbance and more strongly associated with intra-annual temperature fluctuations (seasonality). Our results suggest that climatic factors play a dominant role in driving global variation in the impacts of forest fragmentation, emphasizing the need for more nuanced environmental policies that take into account local context and associated species traits.

  • Journal article
    Baier F, Gauye F, Perez-Carrasco R, Payne JL, Schaerli Yet al., 2023,

    Environment-dependent epistasis increases phenotypic diversity in gene regulatory networks

    , SCIENCE ADVANCES, Vol: 9, ISSN: 2375-2548
  • Journal article
    Winterhalter C, Pelliciari S, Stevens D, Fenyk S, Marchand E, Cronin NB, Soultanas P, Costa TRD, Ilangovan A, Murray Het al., 2023,

    The DNA replication initiation protein DnaD recognises a specific strand of the Bacillus subtilis chromosome origin

    , Nucleic Acids Research, Vol: 51, Pages: 4322-4340, ISSN: 0305-1048

    Genome replication is a fundamental biological activity shared by all organisms. Chromosomal replication proceeds bidirectionally from origins, requiring the loading of two helicases, one for each replisome. However, the molecular mechanisms underpinning helicase loading at bacterial chromosome origins (oriC) are unclear. Here we investigated the essential DNA replication initiation protein DnaD in the model organism Bacillus subtilis. A set of DnaD residues required for ssDNA binding was identified, and photo-crosslinking revealed that this ssDNA binding region interacts preferentially with one strand of oriC. Biochemical and genetic data support the model that DnaD recognizes a new single-stranded DNA (ssDNA) motif located in oriC, the DnaD Recognition Element (DRE). Considered with single particle cryo-electron microscopy (cryo-EM) imaging of DnaD, we propose that the location of the DRE within oriC orchestrates strand-specific recruitment of helicase during DNA replication initiation. These findings significantly advance our mechanistic understanding of bidirectional replication from a bacterial chromosome origin.

  • Journal article
    Malik A, Sayed AA, Han P, Tan MMH, Watt E, Constantinescu-Bercu A, Cocker ATH, Khoder A, Saputil RC, Thorley EV, Teklemichael A, Ding Y, Hart ACJ, Zhang H, Mitchell WA, Imami N, Crawley JTB, Salles-Crawley II, Bussel JB, Zehnder JL, Adams SP, Zhang BM, Cooper Net al., 2023,

    The role of CD8+ T cell clones in immune thrombocytopenia

    , Blood, Vol: 141, Pages: 2417-2429, ISSN: 0006-4971

    Immune thrombocytopenia (ITP) is traditionally considered an antibody-mediated disease. However, a number of features suggest alternative mechanisms of platelet destruction. In this study, we use a multi-dimensional approach to explore the role of cytotoxic CD8+ T cells in ITP. We characterised patients with ITP and compared them to age-matched controls using immunophenotyping, next-generation sequencing of T cell receptor (TCR) genes, single-cell RNA sequencing, and functional T cell and platelet assays. We found that adults with chronic ITP have increased polyfunctional, terminally differentiated effector memory CD8+ T cells (CD45RA+CD62L-) expressing intracellular interferon-g, tumour necrosis factor-a, and Granzyme B defining them as TEMRA cells. These TEMRA cells expand when the platelet count falls and show no evidence of physiological exhaustion. Deep sequencing of the T cell receptor showed expanded T cell clones in patients with ITP. T cell clones persisted over many years, were more prominent in patients with refractory disease, and expanded when the platelet count was low. Combined single-cell RNA and TCR sequencing of CD8+ T cells confirmed that the expanded clones are TEMRA cells. Using in vitro model systems, we show that CD8+ T cells from patients with ITP form aggregates with autologous platelets, release interferon-g and trigger platelet activation and apoptosis through TCR-mediated release of cytotoxic granules. These findings of clonally expanded CD8+ T cells causing platelet activation and apoptosis provide an antibody-independent mechanism of platelet destruction, indicating that targeting specific T-cell clones could be a novel therapeutic approach for patients with refractory ITP.

  • Journal article
    Abubakkar-Waziri H, Kalaiarasan G, Wawman R, Hobbs F, Adcock I, Dilliway C, Fang F, Pain C, Porter A, Bhavsar PK, Ransome E, Savolainen V, Kumar P, Chung KFet al., 2023,

    SARS-CoV2 in public spaces in West London UK during COVID-19 pandemic

    , BMJ Open Respiratory Research, Vol: 10, ISSN: 2052-4439

    Background: Spread of SARS-CoV2 by aerosol is considered an important mode of transmission over distances >2 m, particularly indoors.Objectives: We determined whether SARS-CoV2 could be detected in the air of enclosed/semi-enclosed public spaces.Methods and analysis: Between March 2021 and December 2021 during the easing of COVID-19 pandemic restrictions after a period of lockdown, we used total suspended and size-segregated particulate matter (PM) samplers for the detection of SARS-CoV2 in hospitals wards and waiting areas, on public transport, in a university campus and in a primary school in West London.Results: We collected 207 samples, of which 20 (9.7%) were positive for SARS-CoV2 using quantitative PCR. Positive samples were collected from hospital patient waiting areas, from hospital wards treating patients with COVID-19 using stationary samplers and from train carriages in London underground using personal samplers. Mean virus concentrations varied between 429 500 copies/m3 in the hospital emergency waiting area and the more frequent 164 000 copies/m3 found in other areas. There were more frequent positive samples from PM samplers in the PM2.5 fractions compared with PM10 and PM1. Culture on Vero cells of all collected samples gave negative results.Conclusion: During a period of partial opening during the COVID-19 pandemic in London, we detected SARS-CoV2 RNA in the air of hospital waiting areas and wards and of London Underground train carriage. More research is needed to determine the transmission potential of SARS-CoV2 detected in the air.

  • Report
    Kirkpatrick L, Adjiman C, ApSimon H, Berry A, de Nazelle A, Mijic A, Myers R, Woodward G, Workman Met al., 2023,

    Systems thinking for the transition to zero pollution

    , Systems thinking for the transition to zero pollution, www.imperial.ac.uk/grantham, Publisher: Grantham Institute, 40

    Systems approaches are vital for coordinating decision-making in the face of complex issues because they provide the whole picture view needed to avoid negative unintended consequences and to generate genuine benefits. This paper explains how systems thinking can be used to address environmental pollution and support decision-makers in finding solutions.

  • Journal article
    Terlau JF, Brose U, Boy T, Pawar S, Pinsky M, Hirt MRet al., 2023,

    Predicting movement speed of beetles from body size and temperature

    , MOVEMENT ECOLOGY, Vol: 11, ISSN: 2051-3933
  • Journal article
    Alexander J, Posma J, Scott A, Poynter L, Mason S, Herendi L, Roberts L, McDonald J, Cameron S, Darzi A, Goldin R, Takats Z, Marchesi J, Teare J, Kinross Jet al., 2023,

    Pathobionts in the tumour microbiota predict survival following resection for colorectal cancer

    , Microbiome, Vol: 11, Pages: 1-14, ISSN: 2049-2618

    Background and aimsThe gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes.MethodsA multicentre, prospective observational study was conducted of CRC patients undergoing primary surgical resection in the UK (n = 74) and Czech Republic (n = 61). Analysis was performed using metataxonomics, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), targeted bacterial qPCR and tumour exome sequencing. Hierarchical clustering accounting for clinical and oncological covariates was performed to identify clusters of bacteria and metabolites linked to CRC. Cox proportional hazards regression was used to ascertain clusters associated with disease-free survival over median follow-up of 50 months.ResultsThirteen mucosal microbiota clusters were identified, of which five were significantly different between tumour and paired normal mucosa. Cluster 7, containing the pathobionts Fusobacterium nucleatum and Granulicatella adiacens, was strongly associated with CRC (PFDR = 0.0002). Additionally, tumoral dominance of cluster 7 independently predicted favourable disease-free survival (adjusted p = 0.031). Cluster 1, containing Faecalibacterium prausnitzii and Ruminococcus gnavus, was negatively associated with cancer (PFDR = 0.0009), and abundance was independently predictive of worse disease-free survival (adjusted p = 0.0009). UPLC-MS analysis revealed two major metabolic (Met) clusters. Met 1, composed of medium chain (MCFA), long-chain (LCFA) and very long-chain (VLCFA) fatty acid species, ceramides and lysophospholipids, was negatively associated with CRC (PFDR = 2.61 × 10−11); Met 2, composed of phosphatidylcholine species, nucleosides and amino acids, was strongly associated with CRC (PFDR&

  • Journal article
    Lopez-Romero FA, Stumpf S, Kamminga P, Boehmer C, Pradel A, Brazeau MD, Kriwet Jet al., 2023,

    Shark mandible evolution reveals patterns of trophic and habitat-mediated diversification

    , Communications Biology, Vol: 6, ISSN: 2399-3642

    Environmental controls of species diversity represent a central research focus in evolutionary biology. In the marine realm, sharks are widely distributed, occupying mainly higher trophic levels and varied dietary preferences, mirrored by several morphological traits and behaviours. Recent comparative phylogenetic studies revealed that sharks present a fairly uneven diversification across habitats, from reefs to deep-water. We show preliminary evidence that morphological diversification (disparity) in the feeding system (mandibles) follows these patterns, and we tested hypotheses linking these patterns to morphological specialisation. We conducted a 3D geometric morphometric analysis and phylogenetic comparative methods on 145 specimens representing 90 extant shark species using computed tomography models. We explored how rates of morphological evolution in the jaw correlate with habitat, size, diet, trophic level, and taxonomic order. Our findings show a relationship between disparity and environment, with higher rates of morphological evolution in reef and deep-water habitats. Deep-water species display highly divergent morphologies compared to other sharks. Strikingly, evolutionary rates of jaw disparity are associated with diversification in deep water, but not in reefs. The environmental heterogeneity of the offshore water column exposes the importance of this parameter as a driver of diversification at least in the early part of clade history.

  • Journal article
    Sethi S, Ewers RM, Balakrishnan R, 2023,

    Ecology: correct the digital data divide

    , NATURE, Vol: 617, Pages: 35-35, ISSN: 0028-0836
  • Journal article
    Contreras MP, Pai H, Selvaraj M, Toghani A, Lawson DM, Tumtas Y, Duggan C, Yuen ELH, Stevenson CEM, Harant A, Maqbool A, Wu C-H, Bozkurt TO, Kamoun S, Derevnina Let al., 2023,

    Resurrection of plant disease resistance proteins via helper NLR bioengineering

    , SCIENCE ADVANCES, Vol: 9, ISSN: 2375-2548
  • Journal article
    Dunning J, Burke T, Chan AHH, Chik HYJ, Evans T, Schroeder Jet al., 2023,

    Opposite-sex associations are linked with annual fitness, but sociality is stable over lifetime

    , Behavioral Ecology, Vol: 315, Pages: 315-324, ISSN: 1045-2249

    Animal sociality, an individual’s propensity to associate with others, has fitness consequences through mate choice, for example, directly, by increasing the pool of prospective partners, and indirectly through increased survival, and individuals benefit from both. Annually, fitness consequences are realized through increased mating success and subsequent fecundity. However, it remains unknown whether these consequences translate to lifetime fitness. Here, we quantified social associations and their link to fitness annually and over lifetime, using a multi-generational, genetic pedigree. We used social network analysis to calculate variables representing different aspects of an individual’s sociality. Sociality showed high within-individual repeatability. We found that birds with more opposite-sex associates had higher annual fitness than those with fewer, but this did not translate to lifetime fitness. Instead, for lifetime fitness, we found evidence for stabilizing selection on opposite-sex sociality, and sociality in general, suggesting that reported benefits are only short-lived in a wild population, and that selection favors an average sociality.

  • Journal article
    Rudzite M, Subramoni S, Endres RG, Filloux Aet al., 2023,

    Effectiveness of <i>Pseudomonas aeruginosa</i> type VI secretion system relies on toxin potency and type IV pili-dependent interaction

    , PLOS PATHOGENS, Vol: 19, ISSN: 1553-7366
  • Journal article
    Osborne OG, Dobreva MP, Papadopulos AST, de Moura MSB, Brunello AT, de Queiroz LP, Pennington RT, Lloyd J, Savolainen Vet al., 2023,

    Mapping the root systems of individual trees in a natural community using genotyping-by-sequencing

    , New Phytologist, Vol: 238, Pages: 1305-1317, ISSN: 0028-646X

    •The architecture of root systems is an important driver of plant fitness, competition and ecosystem processes. However, the methodological difficulty of mapping roots hampers the study of these processes. Existing approaches to match individual plants to belowground samples are low throughput and species specific. Here, we developed a scalable sequencing-based method to map the root systems of individual trees across multiple species. We successfully applied it to a tropical dry forest community in the Brazilian Caatinga containing 14 species. • We sequenced all 42 individual shrubs and trees in a 14 × 14 m plot using double-digest restriction site-associated sequencing (ddRADseq). We identified species-specific markers and individual-specific haplotypes from the data. We matched these markers to the ddRADseq data from 100 mixed root samples from across the centre (10 × 10 m) of the plot at four different depths using a newly developed R package. • We identified individual root samples for all species and all but one individual. There was a strong significant correlation between belowground and aboveground size measurements, and we also detected significant species-level root-depth preference for two species. • The method is more scalable and less labour intensive than the current techniques and is broadly applicable to ecology, forestry and agricultural biology.

  • Journal article
    Avendano R, Munoz-Montero S, Rojas-Gatjens D, Fuentes-Schweizer P, Vieto S, Montenegro R, Salvador M, Frew R, Kim J, Chavarria M, Jimenez JIIet al., 2023,

    Production of selenium nanoparticles occurs throughan interconnected pathway of sulphur metabolism andoxidative stress response in Pseudomonas putida KT2440

    , Microbial Biotechnology, Vol: 16, Pages: 931-946, ISSN: 1751-7907

    The soil bacterium Pseudomonas putida KT2440 has been shown to produce selenium nanoparticles aerobically from selenite; however, the molecular actors involved in this process are unknown. Here, through a combination of genetic and analytical techniques, we report the first insights into selenite metabolism in this bacterium. Our results suggest that the reduction of selenite occurs through an interconnected metabolic network involving central metabolic reactions, sulphur metabolism, and the response to oxidative stress. Genes such as sucA, D2HGDH and PP_3148 revealed that the 2-ketoglutarate and glutamate metabolism is important to convert selenite into selenium. On the other hand, mutations affecting the activity of the sulphite reductase decreased the bacteria's ability to transform selenite. Other genes related to sulphur metabolism (ssuEF, sfnCE, sqrR, sqr and pdo2) and stress response (gqr, lsfA, ahpCF and sadI) were also identified as involved in selenite transformation. Interestingly, suppression of genes sqrR, sqr and pdo2 resulted in the production of selenium nanoparticles at a higher rate than the wild-type strain, which is of biotechnological interest. The data provided in this study brings us closer to understanding the metabolism of selenium in bacteria and offers new targets for the development of biotechnological tools for the production of selenium nanoparticles.

  • Journal article
    Dvorak P, Galvao TC, Pflueger-Grau K, Banks AM, de Lorenzo V, Jimenez JIet al., 2023,

    Water potential governs the effector specificity of the transcriptional regulator XylR of Pseudomonas putida

    , Environmental Microbiology, Vol: 25, Pages: 1041-1054, ISSN: 1462-2912

    The biodegradative capacity of bacteria in their natural habitats is affected by water availability. In this work, we have examined the activity and effector specificity of the transcriptional regulator XylR of the TOL plasmid pWW0 of Pseudomonas putida mt-2 for biodegradation of m-xylene when external water potential was manipulated with polyethylene glycol PEG8000. By using non-disruptive luxCDEAB reporter technology, we noticed that the promoter activated by XylR (Pu) restricted its activity and the regulator became more effector-specific towards head TOL substrates when cells were grown under water subsaturation. Such a tight specificity brought about by water limitation was relaxed when intracellular osmotic stress was counteracted by the external addition of the compatible solute glycine betaine. With these facts in hand, XylR variants isolated earlier as effector-specificity responders to the non-substrate 1,2,4-trichlorobenzene under high matric stress were re-examined and found to be unaffected by water potential in vivo. All these phenomena could be ultimately explained as the result of water potential-dependent conformational changes in the A domain of XylR and its effector-binding pocket, as suggested by AlphaFold prediction of protein structures. The consequences of this scenario for the evolution of specificities in regulators and the emergence of catabolic pathways are discussed.

  • Journal article
    Hailu E, Cantillon D, Madrazo C, Rose G, Wheeler PR, Golby P, Adnew B, Gagneux S, Aseffa A, V Gordon S, Comas I, Young DB, Waddell SJ, Larrouy-Maumus G, Berg Set al., 2023,

    Lack of methoxy- mycolates characterizes the geographically restricted lineage 7 of<i> Mycobacterium</i><i> tuberculosis</i> complex

    , MICROBIAL GENOMICS, Vol: 9, ISSN: 2057-5858
  • Journal article
    Oliver T, Kim TD, Trinugroho JP, Cordon-Preciado V, Wijayatilake N, Bhatia A, Rutherford AW, Cardona Londono Tet al., 2023,

    The evolution and evolvability of photosystem II

    , Annual Review of Plant Biology, Vol: 74, ISSN: 1040-2519

    Photosystem II is the water-oxidizing and O2 -evolving enzyme of photosynthesis. How and when this remarkable enzyme arose are fundamental questions in the history of life that have remained difficult to answer. Here, recent advances in our understanding of the origin andevolution of photosystem II are reviewed and discussed in detail. The evolution of photosystem II indicates that water oxidation originated early in the history of life, long before the diversification of cyanobacteria and other major groups of prokaryotes, challenging and transforming current paradigms on the evolution of photosynthesis. We show that photosystem II has remained virtually unchanged for well over three billion years, and yet the nonstop duplication process of the D1 subunit of photosystem II, which controls photochemistry and catalysis, has enabled the enzyme to become adaptable to variable environmental conditions, and even to innovate enzymatic functions beyond water oxidation. It is suggested that this evolvability can be exploited to develop novel light-powered enzymes with the capacity to carry out complex multi-step oxidative transformations for sustainable biocatalysis.

  • Conference paper
    Alexander JL, Posma JM, Scott A, Poynter L, Mason S, Doria L, Roberts L, McDonald JA, Cameron S, Hughes D, Liska V, Susova S, Soucek P, Horneffer V, Gomez-Romero M, Herendi L, Lewis M, Hoyles L, Woolston A, Cunningham D, Darzi A, Gerlinger M, Goldin R, Takats Z, Marchesi J, Teare JP, Kinross JMet al., 2023,

    NETWORKS OF PATHOBIONTS IN THE TUMOUR MUCOSAL NICHE PREDICT SURVIVAL FOLLOWING COLORECTAL CANCER RESECTION

    , Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S469-S470, ISSN: 0016-5085
  • Journal article
    Zitouni-Haouar FE-H, Bidartondo MI, Moreno G, Carlavilla JR, Manjon JL, Neggaz S, Zitouni-Nourine SHet al., 2023,

    Bioclimatic origin shapes phylogenetic structure of Tirmania (Pezizaceae): new species and new record from North Africa

    , Journal of Fungi, Vol: 9, ISSN: 2309-608X

    The phylogenetic relationships among Tirmania were investigated using the internal transcribed spacer (ITS) and large subunit (LSU) regions of the nuclear-encoded ribosomal DNA (rDNA) and compared with morphological and bioclimatic data. The combined analyses of forty-one Tirmania samples from Algeria and Spain supported four lineages corresponding to four morphological species. Besides the two previously described taxa, Tirmania pinoyi and Tirmania nivea, here we describe and illustrate a new species, Tirmania sahariensis sp. nov., which differs from all other Tirmania by its distinct phylogenetic position and its specific combination of morphological features. We also present a first record of Tirmania honrubiae from North Africa (Algeria). Our findings suggest that restrictions imposed by the bioclimatic niche have played a key role in driving the speciation process of Tirmania along the Mediterranean and Middle East.

  • Journal article
    Huang Z, Lai PF, Cocker ATH, Haslam SM, Dell A, Brady HJM, Johnson MRet al., 2023,

    Roles of N-linked glycosylation and glycan-binding proteins in placentation: trophoblast infiltration, immunomodulation, angiogenesis, and pathophysiology

    , Biochemical Society Transactions, Vol: 51, Pages: 639-653, ISSN: 0300-5127

    Protein N-linked glycosylation is a structurally diverse post-translational modification that stores biological information in a larger order of magnitude than other post-translational modifications such as phosphorylation, ubiquitination and acetylation. This gives N-glycosylated proteins a diverse range of properties and allows glyco-codes (glycan-related information) to be deciphered by glycan-binding proteins (GBPs). The intervillous space of the placenta is richly populated with membrane-bound and secreted glycoproteins. Evidence exists to suggest that altering the structural nature of their N-glycans can impact several trophoblast functions, which include those related to interactions with decidual cells. This review summarizes trophoblast-related activities influenced by N-glycan-GBP recognition, exploring how different subtypes of trophoblasts actively adapt to characteristics of the decidualized endometrium through cell-specific expression of N-glycosylated proteins, and how these cells receive decidua-derived signals via N-glycan-GBP interactions. We highlight work on how changes in N-glycosylation relates to the success of trophoblast infiltration, interactions of immunomodulators, and uterine angiogenesis. We also discuss studies that suggest aberrant N-glycosylation of trophoblasts may contribute to the pathogenesis of pregnancy complications (e.g. pre-eclampsia, early spontaneous miscarriages and hydatidiform mole). We propose that a more in-depth understanding of how N-glycosylation shapes trophoblast phenotype during early pregnancy has the potential to improve our approach to predicting, diagnosing and alleviating poor maternal/fetal outcomes associated with placental dysfunction.

  • Patent
    Kourelis J, Marchal C, Kamoun S, 2023,

    MODIFYING THE IMMUNE RESPONSE IN PLANTS

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