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  • Journal article
    Arce A, Cantwell-Jones A, Tansley M, Barnes I, Brace S, Mullin VE, Notton D, Ollerton J, Eatough E, Rhodes MW, Bian X, Hogan J, Hunter T, Jackson S, Whiffin A, Blagoderov V, Broad G, Judd S, Kokkini P, Livermore L, Dixit MK, Pearse WD, Gill Ret al., 2022,

    Signatures of increasing environmental stress in bumblebee wings over the past century: Insights from museum specimens

    , Journal of Animal Ecology, ISSN: 0021-8790

    1. Determining when animal populations have experienced stress in the past is fundamental to understanding how risk factors drive contemporary and future species’ responses to environmental change. For insects, quantifying stress and associating it with environmental factors has been challenging due to a paucity of time-series data and because detectable population-level responses can show varying lag effects. One solution is to leverage historic entomological specimens to detect morphological proxies of stress experienced at the time stressors emerged, allowing us to more accurately determine population responses.2. Here we studied specimens of four bumblebee species, an invaluable group of insect pollinators, from five museums collected across Britain over the 20th century. We calculated the degree of fluctuating asymmetry (FA; random deviations from bilateral symmetry) between the right and left forewings as a potential proxy of developmental stress.3. We: i) investigated whether baseline FA levels vary between species, and how this compares between the first and second half of the century; ii) determined the extent of FA change over the century in the four bumblebee species, and whether this followed a linear or non-linear trend; iii) tested which annual climatic conditions correlated with increased FA in bumblebees.4. Species differed in their baseline FA, with FA being higher in the two species that have recently expanded their ranges in Britain. Overall, FA significantly increased over the century but followed a non-linear trend, with the increase starting c. 1925. We found relatively warm and wet years were associated with higher FA. 5. Collectively our findings show that FA in bumblebees increased over the 20th century and under weather conditions that will likely increase in frequency with climate change. By plotting FA trends and quantifying the contribution of annual climate conditions on past populations, we provide an important step towards impro

  • Journal article
    Wadhawan A, da Silva CJS, Nunes CD, Edwards AM, Dionne MSet al., 2022,

    <i>E. faecalis</i> acquires resistance to antimicrobials and insect immunity via common mechanisms

    <jats:title>Abstract</jats:title><jats:p><jats:italic>Enterococcus faecalis</jats:italic> is an opportunistic pathogen that infects many animal hosts, including insects and mammals. It is an important human pathogen and is often highly drug resistant. Using experimental evolution, we generated <jats:italic>Drosophila</jats:italic>-adapted <jats:italic>E. faecalis</jats:italic> strains, which exhibited immune resistance, resulting in increased <jats:italic>in vivo</jats:italic> growth and virulence. Resistance was characterised by mutations in bacterial pathways responsive to cell-surface stress. <jats:italic>Drosophila</jats:italic>-adapted strains exhibited changes in sensitivity to relevant antimicrobials, including daptomycin and vancomycin. Evolved daptomycin-resistant strains harboured mutations in the same signalling systems, with some strains showing increased virulence similar to <jats:italic>Drosophila</jats:italic>-adapted strains. Our results show that common mechanisms provide a route to resistance to both antimicrobials and host immunity in <jats:italic>E. faecalis</jats:italic> and demonstrate that the selection and emergence of antibiotic resistance <jats:italic>in vivo</jats:italic> does not require antibiotic exposure.</jats:p><jats:sec><jats:title>One sentence summary</jats:title><jats:p>Host interaction can promote antimicrobial resistance and antimicrobial treatment can promote virulence in <jats:italic>E. faecalis</jats:italic>.</jats:p></jats:sec>

  • Journal article
    Meisl G, Xu CK, Taylor JD, Michaels TCT, Levin A, Otzen D, Klenerman D, Matthews S, Linse S, Andreasen M, Knowles TPJet al., 2022,

    Uncovering the universality of self-replication in protein aggregation and its link to disease

    , SCIENCE ADVANCES, Vol: 8, ISSN: 2375-2548
  • Journal article
    Khatri BS, Burt A, 2022,

    A theory of resistance to multiplexed gene drive demonstrates the significant role of weakly deleterious natural genetic variation.

    , Proc Natl Acad Sci U S A, Vol: 119

    Evolution of resistance is a major barrier to successful deployment of gene-drive systems to suppress natural populations, which could greatly reduce the burden of many vector-borne diseases. Multiplexed guide RNAs (gRNAs) that require resistance mutations in all target cut sites are a promising antiresistance strategy since, in principle, resistance would only arise in unrealistically large populations. Using stochastic simulations that accurately model evolution at very large population sizes, we explore the probability of resistance due to three important mechanisms: 1) nonhomologous end-joining mutations, 2) single-nucleotide mutants arising de novo, or 3) single-nucleotide polymorphisms preexisting as standing variation. Our results explore the relative importance of these mechanisms and highlight a complexity of the mutation-selection-drift balance between haplotypes with complete resistance and those with an incomplete number of resistant alleles. We find that this leads to a phenomenon where weakly deleterious naturally occurring variants greatly amplify the probability of multisite resistance compared to de novo mutation. This key result provides design criterion for antiresistance multiplexed systems, which, in general, will need a larger number of gRNAs compared to de novo expectations. This theory may have wider application to the evolution of resistance or evolutionary rescue when multiple changes are required before selection can act.

  • Journal article
    Mohammed NBB, Antonopoulos A, Dell A, Haslam SM, Dimitroff CJet al., 2022,

    The pleiotropic role of galectin-3 in melanoma progression: Unraveling the enigma

    , Advances in Cancer Research, ISSN: 0065-230X

    Melanoma is a highly aggressive skin cancer with poor outcomes associated with distant metastasis. Intrinsic properties of melanoma cells alongside the crosstalk between melanoma cells and surrounding microenvironment determine the tumor behavior. Galectin-3 (Gal-3), a ß-galactoside-binding lectin, has emerged as a major effector in cancer progression, including melanoma behavior. Data from melanoma models and patient studies reveal that Gal-3 expression is dysregulated, both intracellularly and extracellularly, throughout the stages of melanoma progression. This review summarizes the most recent data and hypotheses on Gal-3 and its tumor-modulating functions, highlighting its role in driving melanoma growth, invasion, and metastatic colonization. It also provides insight into potential Gal-3-targeted strategies for melanoma diagnosis and treatment.

  • Journal article
    Chik HYJ, Sparks AM, Schroeder J, Dugdale HLet al., 2022,

    A meta-analysis on the heritability of vertebrate telomere length

    , JOURNAL OF EVOLUTIONARY BIOLOGY, ISSN: 1010-061X
  • Journal article
    Mombrikotb SB, Van Agtmaal M, Johnstone E, Crawley MJ, Gweon HS, Griffiths RI, Bell Tet al., 2022,

    The interactions and hierarchical effects of long-term agricultural stressors on soil bacterial communities

    , ENVIRONMENTAL MICROBIOLOGY REPORTS, Vol: 14, Pages: 711-718, ISSN: 1758-2229
  • Journal article
    Bubeck D, Jin Y, Fyfe PK, Gardner S, Wilmes S, Moraga Iet al., 2022,

    Structural insights into the assembly and activation of the IL-27 signalling complex

    , EMBO Reports, ISSN: 1469-221X

    Interleukin 27 (IL-27) is a heterodimeric cytokine that elicits potent immuno-suppressive responses. Comprised of EBI3 and p28 subunits, IL-27 binds GP130 and IL-27Rα receptor chains to activate the JAK/STAT signalling cascade. However, how these receptors recognize IL-27 and form a complex capable of phosphorylating JAK proteins remains unclear. Here, we used cryo electron microscopy (cryoEM) and AlphaFold2 modelling to solve the structure of the IL-27 receptor recognition complex. Our data show how IL-27 serves as a bridge connecting IL-27Rα (domains 1-2) with GP130 (domains 1-3) to initiate signalling. While both receptors contact the p28 component of the heterodimeric cytokine, EBI3 stabilizes the complex by binding a positively charged surface of IL-27Rα and Domain 1 of GP130. We find that assembly of the IL-27 receptor recognition complex is distinct from both IL-12 and IL-6 cytokine families and provides a mechanistic blueprint for tuning IL-27 pleiotropic actions.

  • Journal article
    Giannos P, Kechagias K, 2022,

    Socio-economic impacts and challenges of the coronavirus pandemic (COVID-19): An updated review

    , Sustainability, ISSN: 2071-1050

    The COVID-19 pandemic has shaken up the socio-economic order on a global scale with interventions designed to curb the spread of the disease bearing multiple and reinforcing impacts on several aspects of economic and social lives. The effects of COVID-19 were diverse and often spilled over different or interdependent industries. Economies were hit top-down and bottom-up while businesses and individuals alike endured significant changes that altered national and international supply and demand trends for products and services. The primary and secondary sectors were especially influenced by supply shortages while services and education were largely demand-driven. Monetary policies were specifically targeted to ease these disruptions while protective measures for employees in many cases constrained business competitiveness. The present study provided a cross-sectoral (primary, secondary, tertiary, and quaternary sectors) outline of the implications and challenges since the start of the crisis, centralising important information and offering a view of the current socioeconomic situation.

  • Journal article
    Singh S, Wilksch JJ, Dunstan RA, Mularski A, Wang N, Hocking D, Jebeli L, Cao H, Clements A, Jenney AWJ, Lithgow T, Strugnell RAet al., 2022,

    LPS O Antigen Plays a Key Role in Klebsiella pneumoniae Capsule Retention

    , MICROBIOLOGY SPECTRUM, ISSN: 2165-0497
  • Journal article
    Whyte CE, Singh K, Burton OT, Aloulou M, Kouser L, Veiga RV, Dashwood A, Okkenhaug H, Benadda S, Moudra A, Bricard O, Lienart S, Bielefeld P, Roca CP, Naranjo-Galindo FJ, Lombard-Vadnais F, Junius S, Bending D, Ono M, Hochepied T, Halim TYF, Schlenner S, Lesage S, Dooley J, Liston Aet al., 2022,

    Correction: Context-dependent effects of IL-2 rewire immunity into distinct cellular circuits.

    , J Exp Med, Vol: 219
  • Journal article
    Dobson B, Barry S, Maes-Prior R, Mijic A, Woodward G, Pearse WDet al., 2022,

    Predicting catchment suitability for biodiversity at national scales

    , WATER RESEARCH, Vol: 221, ISSN: 0043-1354
  • Journal article
    Larrouy-Maumus G, Thomson M, Nunta K, Liu Y, Fernandes N, Williams R, garza-garcia Aet al., 2022,

    Expression of a novel mycobacterial phosphodiesterase successfully lowers cAMP levels resulting in reduced tolerance to cell wall-targeting antimicrobials

    , Journal of Biological Chemistry, Vol: 298, ISSN: 0021-9258

    Antimicrobial tolerance, the ability to survive exposure to antimicrobials via transient nonspecific means, promotes the development of antimicrobial resistance (AMR). The study of the molecular mechanisms that result in antimicrobial tolerance is therefore essential for the understanding of AMR. In gram-negative bacteria, the second messenger molecule 3’,5’-cyclic adenosine monophosphate (cAMP) has been previously shown to be involved in AMR. In mycobacteria, however, the role of cAMP in antimicrobial tolerance has been difficult to probe due to its particular complexity. In order to address this difficulty, here, through an unbiased biochemical approaches consisting in the fractionation of clear protein lysate from a mycobacterial strain deleted for the known cAMP phosphodiesterase (Rv0805c) combined with mass spectrometry techniques, we identified a novel cyclic nucleotide-degrading phosphodiesterase enzyme (Rv1339) and developed a system to significantly decrease intracellular cAMP levels through plasmid expression of Rv1339 using the constitutive expression system, pVV16. In Mycobacterium smegmatis mc2155, we demonstrate that recombinant expression of Rv1339 reduced cAMP levels 3-fold and resulted in altered gene expression, impaired bioenergetics and a disruption in peptidoglycan biosynthesis leading to decreased tolerance to antimicrobials that target cell wall synthesis such as ethambutol, D-cycloserine and vancomycin. This work increases our understanding of the role of cAMP in mycobacterial antimicrobial tolerance and our observations suggest that nucleotide signaling may represent a new target for the development of antimicrobial therapies.

  • Journal article
    Dong N, Prentice IC, Wright IJ, Wang H, Atkins OK, Bloomfield KJ, Domingues TF, Gleason SM, Maire V, Onoda Y, Poorter H, Smith NGet al., 2022,

    Leaf nitrogen from the perspective of optimal plant function.

    , Journal of Ecology, ISSN: 0022-0477

    1. Leaf dry mass per unit area (LMA), carboxylation capacity (Vcmax) and leaf nitrogen per unit area (Narea) and mass (Nmass) are key traits for plant functional ecology and ecosystem modelling. There is however no consensus about how these traits are regulated, or how they should be modelled. Here we confirm that observed leaf nitrogen across species and sites can be estimated well from observed LMA and Vcmax at 25˚C (Vcmax25). We then test the hypothesis that global variations of both quantities depend on climate variables in specific ways that are predicted by leaf-level optimality theory, thus allowing both Narea to be predicted as functions of the growth environment.2. A new global compilation of field measurements was used to quantify the empirical relationships of leaf N to Vcmax25 and LMA. Relationships of observed Vcmax25 and LMA to climate variables were estimated, and compared to independent theoretical predictions of these relationships. Soil effects were assessed by analysing biases in the theoretical predictions.3. LMA was the most important predictor of Narea (increasing) and Nmass (decreasing). About 60% of global variation across species and sites in observed Narea, and 31% in Nmass, could be explained by observed LMA and V¬cmax25. These traits in turn were quantitatively related to climate variables, with significant partial relationships similar or indistinguishable from those predicted by optimality theory. Predicted trait values explained 21% of global variation in observed site-mean Vcmax25, 43% in LMA, and 31% in Narea. Predicted Vcmax25 was biased low on clay-rich soils but predicted LMA was biased high, with compensating effects on Narea. Narea was overpredicted on organic soils.4. Synthesis. Global patterns of variation in observed site-mean Narea can be explained by climate-induced variations in optimal Vcmax25¬ and LMA. Leaf nitrogen should accordingly be modelled as a consequence (not a cause) of Vcmax25 and LMA, both being optim

  • Journal article
    Kowal J, Arrigoni E, Jarvis S, Zappala S, Forbes E, Bidartondo MI, Suz LMet al., 2022,

    Atmospheric pollution, soil nutrients and climate effects on Mucoromycota arbuscular mycorrhizal fungi

    , Environmental Microbiology, Vol: 24, Pages: 3390-3404, ISSN: 1462-2912

    Fine root endophyte mycorrhizal fungi in the Endogonales (Mucoromycota arbuscular mycorrhizal fungi, M-AMF) are now recognized as at least as important globally as Glomeromycota AMF (G-AMF), yet little is known about the environmental factors which influence M-AMF diversity and colonization, partly because they typically only co-colonize plants with G-AMF. Wild populations of Lycopodiella inundata predominantly form mycorrhizas with M-AMF and therefore allow focussed study of M-AMF environmental drivers. Using microscopic examination and DNA sequencing we measured M-AMF colonization and diversity over three consecutive seasons and modelled interactions between these response variables and environmental data. Significant relationships were found between M-AMF colonization and soil S, P, C:N ratio, electrical conductivity, and the previously overlooked micronutrient Mn. Estimated N deposition was negatively related to M-AMF colonization. Thirty-nine Endogonales Operational Taxonomic Units (OTUs) were identified in L. inundata roots, a greater diversity than previously recognized in this plant. Endogonales OTU richness correlated negatively with soil C:N while community composition was mostly influenced by soil P. This study provides first evidence that M-AMF have distinct ecological preferences in response to edaphic variables also related to air pollution. Future studies require site-level atmospheric pollution monitoring to guide critical load policy for mycorrhizal fungi in heathlands and grasslands.

  • Journal article
    Wincott CJ, Sritharan G, Benns HJ, May D, Gilabert-Carbajo C, Bunyan M, Fairweather AR, Alves E, Andrew I, Game L, Frickel E-M, Tiengwe C, Ewald SE, Child MAet al., 2022,

    Cellular barcoding of protozoan pathogens reveals the within-host population dynamics of Toxoplasma gondii host colonization

    , Cell Reports Methods, Vol: 2, Pages: 1-16, ISSN: 2667-2375

    Cellular barcoding techniques are powerful tools to understand microbial pathogenesis. However, barcoding strategies have not been broadly applied to protozoan parasites, which have unique genomic structures and virulence strategies compared with viral and bacterial pathogens. Here, we present a CRISPR-based method to barcode protozoa, which we successfully apply to Toxoplasma gondii and Trypanosoma brucei. Using libraries of barcoded T. gondii, we evaluate shifts in the population structure from acute to chronic infection of mice. Contrary to expectation, most barcodes were present in the brain one month post-intraperitoneal infection in both inbred CBA/J and outbred Swiss mice. Although parasite cyst number and barcode diversity declined over time, barcodes representing a minor fraction of the inoculum could become a dominant population in the brain by three months post-infection. These data establish a cellular barcoding approach for protozoa and evidence that the blood-brain barrier is not a major bottleneck to colonization by T. gondii.

  • Journal article
    Giannos P, 2022,

    Associations of bioavailable serum testosterone with cognitive function in older men: results from the National Health and Nutrition Examination Survey

    , The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, ISSN: 1079-5006

    Background: Age-associated cognitive decline may be influenced by testosterone status. However, studies evaluating the impact of bioavailable testosterone, the active, free testosterone, on cognitive function are scarce. Our study determined the relationship between calculated bioavailable testosterone and cognitive performance in older men.Methods: We used data from the US National Health and Nutrition Examination Survey (NHANES) between 2013 and 2014. This study consisted of 208 men aged ≥ 60 years. Bioavailable serum testosterone was calculated based on the total serum testosterone, sex hormone-binding globulin, and albumin levels, while cognitive performance was assessed through the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Learning Test (WLLT), Word List Recall Test (WLRT), and Intrusion Word Count Test (WLLT-IC and WLRT-IC), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Multiple linear regression analyses were performed upon adjustment for age, ethnicity, socio-economic status, education level, medical history, body mass index, energy, alcohol intake, physical activity levels and sleep duration.Results: A significant positive association between bioavailable testosterone and DSST (β: 0.049, P=0.002) score was detected, with no signs of a plateau effect. No significant associations with CERAD WLLT (P=0.132), WLRT (P=0.643), WLLT-IC (P=0.979), and WLRT-IC (P=0.387), and AFT (P=0.057) were observed. Conclusion: Calculated bioavailable testosterone presented a significant positive association with processing speed, sustained attention and working memory in older men above 60 years of age. Further research is warranted to elucidate the impact of the inevitable age-related decline in testosterone on cognitive function in older men.

  • Journal article
    Windbichler N, 2022,

    Gene drive mosquitoes can aid malaria elimination by retarding Plasmodium sporogonic development

    , Science Advances, ISSN: 2375-2548

    Abstract: Gene drives hold promise for the genetic control of malaria vectors. The development of vector population modification strategies hinges on the availability of effector mechanisms impeding parasite development in transgenic mosquitoes. We augmented a midgut gene of the malaria mosquito Anopheles gambiae to secrete two exogenous antimicrobial peptides, Magainin 2 and Melittin. This small genetic modification, capable of efficient non-autonomous gene drive, hampers oocyst development in both Plasmodium falciparum and Plasmodium berghei. It delays the release of infectious sporozoites while it simultaneously reduces the lifespan of homozygous female transgenic mosquitoes. Modeling the spread of this modification using a large-scale agent-based model of malaria epidemiology reveals that it can break the cycle of disease transmission across a range of transmission intensities.

  • Journal article
    Vitale M, Leo C, Courty T, Kranjc N, Connolly JB, Morselli G, Bamikole C, Haghighat-Khah RE, Bernardini F, Fuchs Set al., 2022,

    Comprehensive characterization of a transgene insertion in a highly repetitive, centromeric region of Anopheles mosquitoes

    , Pathogens and Global Health, ISSN: 2047-7724

    The availability of the genomic sequence of the malaria mosquito Anopheles gambiae has in recent years sparked the development of transgenic technologies with the potential to be used as novel vector control tools. These technologies rely on genome editing that confer traits able to affect vectorial capacity. This can be achieved by either reducing the mosquito population or by making mosquitoes refractory to the parasite infection. For any genetically modified organism that is regarded for release, molecular characterization of the transgene and flanking sites are essential for their safety assessment and post-release monitoring. Despite great advancements, Whole-Genome Sequencing data are still subject to limitations due to the presence of repetitive and unannotated DNA sequences. Faced with this challenge, we describe a number of techniques that were used to identify the genomic location of a transgene in the male bias mosquito strain Ag(PMB)1 considered for potential field application. While the initial inverse PCR identified the most likely insertion site on Chromosome 3 R 36D, reassessment of the data showed a high repetitiveness in those sequences and multiple genomic locations as potential insertion sites of the transgene. Here we used a combination of DNA sequencing analysis and in-situ hybridization to clearly identify the integration of the transgene in a poorly annotated centromeric region of Chromosome 2 R 19D. This study emphasizes the need for accuracy in sequencing data for the genome of organisms of medical importance such as Anopheles mosquitoes and other tools available that can support genomic locations of transgenes.

  • Journal article
    Chukhutsina VU, van Thor JJ, 2022,

    Molecular Activation Mechanism and Structural Dynamics of Orange Carotenoid Protein

    , Physchem, Vol: 2, Pages: 235-252

    <jats:p>Like most photosynthetic organisms, cyanobacteria are vulnerable to fluctuations in light intensity, which can damage their photosynthetic machinery. To protect against this, they use a photoprotective mechanism called non-photochemical quenching (NPQ), where excess absorbed photo-energy is dissipated as heat. In cyanobacteria, light activation of Orange Carotenoid Protein (OCP) is the critical first step in the NPQ response. OCP is also the only known photosensitive protein, which uses carotenoid for its activation. We summarize the current knowledge on the light induced reactions of OCP; the different mechanisms of activation that have been proposed; photocycle kinetics and characteristics; and the reported structural intermediates. We discuss the possible interpretations of reported experimental results, and we formulate important open questions and directions for future work, to reveal the molecular and structural basis of photosensing by OCP.</jats:p>

  • Journal article
    Brosh O, Fabian DK, Cogni R, Tolosana I, Day JP, Olivieri F, Merckx M, Akilli N, Szkuta P, Jiggins FMet al., 2022,

    A novel transposable element-mediated mechanism causes antiviral resistance in Drosophila through truncating the Veneno protein.

    , Proc Natl Acad Sci U S A, Vol: 119

    Hosts are continually selected to evolve new defenses against an ever-changing array of pathogens. To understand this process, we examined the genetic basis of resistance to the Drosophila A virus in Drosophila melanogaster. In a natural population, we identified a polymorphic transposable element (TE) insertion that was associated with an ∼19,000-fold reduction in viral titers, allowing flies to largely escape the harmful effects of infection by this virulent pathogen. The insertion occurs in the protein-coding sequence of the gene Veneno, which encodes a Tudor domain protein. By mutating Veneno with CRISPR-Cas9 in flies and expressing it in cultured cells, we show that the ancestral allele of the gene has no effect on viral replication. Instead, the TE insertion is a gain-of-function mutation that creates a gene encoding a novel resistance factor. Viral titers remained reduced when we deleted the TE sequence from the transcript, indicating that resistance results from the TE truncating the Veneno protein. This is a novel mechanism of virus resistance and a new way by which TEs can contribute to adaptation.

  • Journal article
    Kaplan M, Oikonomou CM, Wood CR, Chreifi G, Ghosal D, Dobro MJ, Yao Q, Pal RR, Baidya AK, Liu Y, Maggi S, McDowall AW, Ben-Yehuda S, Rosenshine I, Briegel A, Beeby M, Chang Y-W, Shaffer CL, Jensen GJet al., 2022,

    Discovery of a Novel Inner Membrane-Associated Bacterial Structure Related to the Flagellar Type III Secretion System

    , JOURNAL OF BACTERIOLOGY, Vol: 204, ISSN: 0021-9193
  • Journal article
    Musasia FK, Nkumama IN, Frank R, Kipkemboi V, Schneider M, Mwai K, Odera DO, Rosenkranz M, Fürle K, Kimani D, Tuju J, Njuguna P, Hamaluba M, Kapulu MC, Wardemann H, CHMI-SIKA Study Team, Osier FHAet al., 2022,

    Phagocytosis of Plasmodium falciparum ring-stage parasites predicts protection against malaria.

    , Nature Communications, Vol: 13, Pages: 1-12, ISSN: 2041-1723

    Ring-infected erythrocytes are the predominant asexual stage in the peripheral circulation but are rarely investigated in the context of acquired immunity against Plasmodium falciparum malaria. Here we compare antibody-dependent phagocytosis of ring-infected parasite cultures in samples from a controlled human malaria infection (CHMI) study (NCT02739763). Protected volunteers did not develop clinical symptoms, maintained parasitaemia below a predefined threshold of 500 parasites/μl and were not treated until the end of the study. Antibody-dependent phagocytosis of both ring-infected and uninfected erythrocytes from parasite cultures was strongly correlated with protection. A surface proteomic analysis revealed the presence of merozoite proteins including erythrocyte binding antigen-175 and -140 on ring-infected and uninfected erythrocytes, providing an additional antibody-mediated protective mechanism for their activity beyond invasion-inhibition. Competition phagocytosis assays support the hypothesis that merozoite antigens are the key mediators of this functional activity. Targeting ring-stage parasites may contribute to the control of parasitaemia and prevention of clinical malaria.

  • Journal article
    Rubin C-J, Enbody ED, Dobreva MP, Abzhanov A, Davis BW, Lamichhaney S, Pettersson M, Sendell-Price AT, Sprehn CG, Valle CA, Vasco K, Wallerman O, Grant BR, Grant PR, Andersson Let al., 2022,

    Rapid adaptive radiation of Darwin's finches depends on ancestral genetic modules

    , SCIENCE ADVANCES, Vol: 8, ISSN: 2375-2548
  • Journal article
    Barker J, Davies J, Goralczyk M, Patel S, O'Connor J, Evans J, Sharp R, Gollock M, Wood FR, Rosindell J, Bartlett C, Garner BJ, Jones D, Quigley D, Wray Bet al., 2022,

    The distribution, ecology and predicted habitat use of the Critically Endangered angelshark (Squatina squatina) in coastal waters of Wales and the central Irish Sea

    , JOURNAL OF FISH BIOLOGY, Vol: 101, Pages: 640-658, ISSN: 0022-1112
  • Journal article
    Zhang K, Li S, Wang Y, Wang Z, Mulvenna N, Yang H, Zhang P, Chen H, Li Y, Wang H, Gao Y, Wigneshweraraj S, Matthews S, Zhang K, Liu Bet al., 2022,

    Bacteriophage protein PEIP is a potent Bacillus subtilis enolase inhibitor

    , CELL REPORTS, Vol: 40, ISSN: 2211-1247
  • Journal article
    Cheng S, Jin Y, Harrison S, Quilodrán Casas C, Prentice C, Guo Y-K, Arcucci Ret al., 2022,

    Parameter flexible wildfire prediction using machine learning techniques: forward and inverse modelling

    , Remote Sensing, Vol: 14, ISSN: 2072-4292

    Parameter identification for wildfire forecasting models often relies on case-by-case tuning or posterior diagnosis/analysis, which can be computationally expensive due to the complexity of the forward prediction model. In this paper, we introduce an efficient parameter flexible fire prediction algorithm based on machine learning and reduced order modelling techniques. Using a training dataset generated by physics-based fire simulations, the method forecasts burned area at different time steps with a low computational cost. We then address the bottleneck of efficient parameter estimation by developing a novel inverse approach relying on data assimilation techniques (latent assimilation) in the reduced order space. The forward and the inverse modellings are tested on two recent large wildfire events in California. Satellite observations are used to validate the forward prediction approach and identify the model parameters. By combining these forward and inverse approaches, the system manages to integrate real-time observations for parameter adjustment, leading to more accurate future predictions.

  • Journal article
    Chaukimath P, Frankel G, Visweswariah SS, 2022,

    The metabolic impact of bacterial infection in the gut

    , FEBS JOURNAL, ISSN: 1742-464X
  • Journal article
    Giannos P, 2022,

    Altered mitochondrial microenvironment at the spotlight of musculoskeletal aging and Alzheimer’s disease

    , Scientific Reports, Vol: 12, ISSN: 2045-2322

    Emerging evidence has linked Alzheimer’s disease (AD) onset with musculoskeletal aging via a muscle-brain crosstalk mediated by dysregulation of the mitochondrial microenvironment. This study investigated gene expression profiles from skeletal muscle tissues of older healthy adults to identify potential gene biomarkers whose dysregulated expression and protein interactome were involved in AD. Screening of the literature resulted in 12 relevant microarray datasets (GSE25941, GSE28392, GSE28422, GSE47881, GSE47969, GSE59880) in musculoskeletal aging and (GSE4757, GSE5281, GSE16759, GSE28146, GSE48350, GSE84422) in AD. Retrieved differentially expressed genes (DEGs) were used to construct two unique protein-protein interaction (PPI) networks and clustering gene modules were identified. Overlapping module DEGs in the musculoskeletal aging and AD networks were ranked based on 11 topological algorithms and the five highest-ranked ones were considered as hub genes. The analysis revealed that the dysregulated expression of the mitochondrial microenvironment genes, NDUFAB1, UQCRC1, UQCRFS1, NDUFS3, and MRPL15, overlapped between both musculoskeletal aging and AD networks. Thus, these genes may have a potential role as markers of AD occurrence in musculoskeletal aging. Human studies are warranted to evaluate the functional role and prognostic value of these genes in aging populations with sarcopenia and AD.

  • Journal article
    Whyte CE, Singh K, Burton OT, Aloulou M, Kouser L, Veiga RV, Dashwood A, Okkenhaug H, Benadda S, Moudra A, Bricard O, Lienart S, Bielefeld P, Roca CP, Naranjo-Galindo FJ, Lombard-Vadnais F, Junius S, Bending D, Ono M, Hochepied T, Halim TYF, Schlenner S, Lesage S, Dooley J, Liston Aet al., 2022,

    Context-dependent effects of IL-2 rewire immunity into distinct cellular circuits.

    , J Exp Med, Vol: 219

    Interleukin 2 (IL-2) is a key homeostatic cytokine, with therapeutic applications in both immunogenic and tolerogenic immune modulation. Clinical use has been hampered by pleiotropic functionality and widespread receptor expression, with unexpected adverse events. Here, we developed a novel mouse strain to divert IL-2 production, allowing identification of contextual outcomes. Network analysis identified priority access for Tregs and a competitive fitness cost of IL-2 production among both Tregs and conventional CD4 T cells. CD8 T and NK cells, by contrast, exhibited a preference for autocrine IL-2 production. IL-2 sourced from dendritic cells amplified Tregs, whereas IL-2 produced by B cells induced two context-dependent circuits: dramatic expansion of CD8+ Tregs and ILC2 cells, the latter driving a downstream, IL-5-mediated, eosinophilic circuit. The source-specific effects demonstrate the contextual influence of IL-2 function and potentially explain adverse effects observed during clinical trials. Targeted IL-2 production therefore has the potential to amplify or quench particular circuits in the IL-2 network, based on clinical desirability.

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