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Journal articleYuen ELH, Leary AY, Clavel M, et al., 2024,
A RabGAP negatively regulates plant autophagy and immune trafficking.
, Curr Biol, Vol: 34, Pages: 2049-2065.e6Plants rely on autophagy and membrane trafficking to tolerate stress, combat infections, and maintain cellular homeostasis. However, the molecular interplay between autophagy and membrane trafficking is poorly understood. Using an AI-assisted approach, we identified Rab3GAP-like (Rab3GAPL) as a key membrane trafficking node that controls plant autophagy negatively. Rab3GAPL suppresses autophagy by binding to ATG8, the core autophagy adaptor, and deactivating Rab8a, a small GTPase essential for autophagosome formation and defense-related secretion. Rab3GAPL reduces autophagic flux in three model plant species, suggesting that its negative regulatory role in autophagy is conserved in land plants. Beyond autophagy regulation, Rab3GAPL modulates focal immunity against the oomycete pathogen Phytophthora infestans by preventing defense-related secretion. Altogether, our results suggest that Rab3GAPL acts as a molecular rheostat to coordinate autophagic flux and defense-related secretion by restraining Rab8a-mediated trafficking. This unprecedented interplay between a RabGAP-Rab pair and ATG8 sheds new light on the intricate membrane transport mechanisms underlying plant autophagy and immunity.
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Journal articleGayford J, Brazeau M, Naylor GJP, 2024,
Evolutionary trends in the elasmobranch neurocranium
, Scientific Reports, Vol: 14, ISSN: 2045-2322The neurocranium (braincase) is one of the defining vertebrate characters. Housing the brain and other key sensory organs, articulating with the jaws and contributing to the shape of the anteriormost portion of the body, the braincase is undoubtedly of great functional importance. Through studying relationships between braincase shape and ecology we can gain an improved understanding of form-function relationships in extant and fossil taxa. Elasmobranchii (sharks and rays) represent an important case study of vertebrate braincase diversity as their neurocranium is simplified and somewhat decoupled from other components of the cranium relative to other vertebrates. Little is known about the associations between ecology and braincase shape in this clade. In this study we report patterns of mosaic cranial evolution in Elasmobranchii that differ significantly from those present in other clades. The degree of evolutionary modularity also differs between Selachii and Batoidea. In both cases innovation in the jaw suspension appears to have driven shifts in patterns of integration and modularity, subsequently facilitating ecological diversification. Our results confirm the importance of water depth and biogeography as drivers of elasmobranch cranial diversity and indicate that skeletal articulation between the neurocranium and jaws represents a major constraint upon the evolution of braincase shape in vertebrates.
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Journal articleFecht S, Paracuellos P, Subramoni S, et al., 2024,
Functionality of chimeric TssA proteins in the type VI secretion system reveals sheath docking specificity within their N-terminal domains
, Nature Communications, Vol: 15, ISSN: 2041-1723The genome of Pseudomonas aeruginosa encodes three type VI secretion systems, each comprising a dozen distinct proteins, which deliver toxins upon T6SS sheath contraction. The least conserved T6SS component, TssA, has variations in size which influence domain organisation and structure. Here we show that the TssA Nt1 domain interacts directly with the sheath in a specific manner, while the C-terminus is essential for oligomerisation. We built chimeric TssA proteins by swapping C-termini and showed that these can be functional even when made of domains from different TssA sub-groups. Functional specificity requires the Nt1 domain, while the origin of the C-terminal domain is more permissive for T6SS function. We identify two regions in short TssA proteins, loop and hairpin, that contribute to sheath binding. We propose a docking mechanism of TssA proteins with the sheath, and a model for how sheath assembly is coordinated by TssA proteins from this position.
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Journal articleCreamer A, Lo Fiego A, Agliano A, et al., 2024,
Modular synthesis of semiconducting graft co-polymers to achieve ‘clickable’ fluorescent nanoparticles with long circulation and specific cancer targeting
, Advanced Materials, Vol: 36, Pages: 1-14, ISSN: 0935-9648Semiconducting polymer nanoparticles (SPNs) are explored for applications in cancer theranostics because of their high absorption coefficients, photostability, and biocompatibility. However, SPNs are susceptible to aggregation and protein fouling in physiological conditions, which can be detrimental for in vivo applications. Here, a method for achieving colloidally stable and low-fouling SPNs is described by grafting poly(ethylene glycol) (PEG) onto the backbone of the fluorescent semiconducting polymer, poly(9,9′-dioctylfluorene-5-fluoro-2,1,3-benzothiadiazole), in a simple one-step substitution reaction, postpolymerization. Further, by utilizing azide-functionalized PEG, anti-human epidermal growth factor receptor 2 (HER2) antibodies, antibody fragments, or affibodies are site-specifically “clicked” onto the SPN surface, which allows the functionalized SPNs to specifically target HER2-positive cancer cells. In vivo, the PEGylated SPNs are found to have excellent circulation efficiencies in zebrafish embryos for up to seven days postinjection. SPNs functionalized with affibodies are then shown to be able to target HER2 expressing cancer cells in a zebrafish xenograft model. The covalent PEGylated SPN system described herein shows great potential for cancer theranostics.
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Journal articleCoatsworth P, Cotur Y, Asfour T, et al., 2024,
Plant-on-a-chip: continuous, soilless electrochemical monitoring of salt uptake and tolerance among different genotypes of tomato
, SENSORS & DIAGNOSTICS, Vol: 3 -
Journal articleNguyen H-TT, Zhao M, Wang T, et al., 2024,
Sea anemone-anemonefish symbiosis: Behavior and mucous protein profiling
, JOURNAL OF FISH BIOLOGY, ISSN: 0022-1112 -
Journal articleMiao A, Luo T, Hsieh B, et al., 2024,
Brain clearance is reduced during sleep and anesthesia
, Nature Neuroscience, Vol: 27, Pages: 1046-1050, ISSN: 1097-6256It has been suggested that the function of sleep is to actively clear metabolites and toxins from the brain. Enhanced clearance is also said to occur during anesthesia. Here, we measure clearance and movement of fluorescent molecules in the brains of male mice and show that movement is, in fact, independent of sleep and wake or anesthesia. Moreover, we show that brain clearance is markedly reduced, not increased, during sleep and anesthesia.
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Journal articlePirzio-Biroli A, Crowley SL, Siriwardena GM, et al., 2024,
Not in the countryside please! Investigating UK residents’ perceptions of an introduced species, the ring-necked parakeet (Psittacula krameri)
, NeoBiota, Vol: 93, Pages: 1-24, ISSN: 1314-2488Wildlife management can generate social conflict when stakeholder perceptions of the target species are not considered. Introduced Ring-necked Parakeets (RNP) are established in the UK and have been added to the ‘general licence’ of birds that can be killed to prevent serious economic damage. We aimed to better understand perceptions of RNPs on a nationwide scale to inform mitigation actions for potential future conflict over RNP management. We surveyed 3,947 UK residents to understand awareness of, knowledge of and attitudes towards the RNP across the UK.We found that most respondents (90.2%) were aware of the RNP. Almost half of respondents (45.9%) held negative opinions, particularly against the RNP in rural areas (64.7%), suggesting landscape contexts influence attitudes. Respondent preference for the RNP was low in local neighbourhoods (7.80%) although the species was considered aesthetically pleasing by most (83.0%). Many respondents knew the species’ name (54.9%), but underestimated current population numbers in the UK (82.6%) and few knew its full native range (10.0%). We identified respondents’ ecological interest, age, education, preference for, awareness of and knowledge of the RNP as significant factors associated with perceptions.Our findings suggest that the RNP presents a complex socio-environmental challenge, with respondent awareness, knowledge and attitudes each forming an important component of perceptions towards this species. We recommend that wildlife managers utilise our findings and cohesive approach to enhance future RNP perception research in the UK and abroad and towards the success of any proposed management initiatives under the UK general licence.
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Journal articleZhu Y, Xi J, Yao Y, et al., 2024,
Characterizing the dynamic linkages between environmental changes and wheat Fusarium head blight epidemics
, Ecological Informatics, Vol: 80, ISSN: 1574-9541Fusarium head blight (FHB) is a prevalent wheat disease, mainly influenced by environmental factors, such as irradiance, temperature, precipitation, and CO2 levels. Elucidating the relationship between FHB outbreaks and environmental changes is crucial for predictive models and control measures. This study employs historical data to map the dynamic associations between environmental changes and FHB epidemics within a phase space. Complex networks are constructed to analyze the dynamic relationships, followed by an examination and clustering of their topological features and a discussion of similarities and differences. The results revealed structural similarities between the impact of precipitation and CO2 on FHB, as well as between temperature and irradiance on FHB. In addition, precipitation consistently exerts a persistent and sensitive influence on FHB epidemics, while temperature exhibits an inverse relationship. Elevated carbon emissions enhance the effect of CO2 on FHB, while the effect of irradiance on FHB epidemics varies with the solar cycle. This study provides a novel approach to detect and understand the dynamic relationships between FHB epidemics and environmental changes, contributing to enhanced disease surveillance and assessment within complex agriculture systems.
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Journal articleLo E, Nie R-E, Vogler AP, 2024,
The geographic and phylogenetic structure of public DNA barcode databases: an assessment using Chrysomelidae (leaf beetles)
, FRONTIERS IN ECOLOGY AND EVOLUTION, Vol: 12, ISSN: 2296-701X -
Journal articleCorti R, Piazza E, Armelloni EN, et al., 2024,
A multidisciplinary approach to describe population structure of <i>Solea solea</i> in the Mediterranean Sea
, FRONTIERS IN MARINE SCIENCE, Vol: 11 -
Journal articleSun Y, Dunning J, Taylor T, et al., 2024,
Calls of Manx shearwater <i>Puffinus puffinus</i> contain individual signatures
, JOURNAL OF AVIAN BIOLOGY, Vol: 2024, ISSN: 0908-8857 -
Journal articleLewis-Brown E, Jennings N, Mills M, et al., 2024,
Comparison of carbon management and emissions of universities that did and did not adopt voluntary carbon offsets
, Climate Policy, Vol: 24, Pages: 706-722, ISSN: 1469-3062The urgent need to reduce greenhouse gas emissions, remove carbon from the atmosphere and stabilize natural carbon sinks has led to the development of many carbon management measures, increasingly including voluntary carbon offsets (VCOs). We studied carbon management in universities, institutions with large carbon footprints and considerable influence in climate science and policy fora. However, concerns that VCOs may deter adopters (including universities) from adopting other carbon reduction measures and limit emissions reductions, for example, through moral hazard, have been raised but understudied. We compared the carbon management characteristics (priorities, policies, practices and emissions) of universities that did and did not adopt VCOs. We found adopters measured carbon emissions for longer, and had set targets to reach net zero earlier than had non-adopters. Adopters of VCOs also undertook more carbon management practices in both 2010 and 2020 than non-adopters. We also found that both adopters and non-adopters significantly increased their carbon management practices over the decade studied, but with no difference between groups. Gross CO2 emissions were reduced significantly over time by adopters of VCOs but not by non-adopters, whereas carbon intensity and percentage annual emissions reductions did not relate to adoption status. Consequently, our study showed no indication of mitigation deterrence due to adoption of VCOs at the universities studied. Rather, greater emissions reductions correlated with earlier net zero target dates, and a higher number of policies and carbon management practices. However, our study was constrained to universities that were affiliated with a national environmental network, so research beyond these organizations, and with individuals, would be useful. The survey was voluntary, exposing the study to potential self-selection bias so the findings may not be generalized beyond the study group. Finally, we found the carbon ac
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Journal articleMerckx VSFT, Gomes SIF, Wang D, et al., 2024,
Mycoheterotrophy in the wood-wide web
, Nature Plants, Vol: 10, Pages: 710-718, ISSN: 2055-026XThe prevalence and potential functions of common mycorrhizal networks, or the 'wood-wide web', resulting from the simultaneous interaction of mycorrhizal fungi and roots of different neighbouring plants have been increasingly capturing the interest of science and society, sometimes leading to hyperbole and misinterpretation. Several recent reviews conclude that popular claims regarding the widespread nature of these networks in forests and their role in the transfer of resources and information between plants lack evidence. Here we argue that mycoheterotrophic plants associated with ectomycorrhizal or arbuscular mycorrhizal fungi require resource transfer through common mycorrhizal networks and thus are natural evidence for the occurrence and function of these networks, offering a largely overlooked window into this methodologically challenging underground phenomenon. The wide evolutionary and geographic distribution of mycoheterotrophs and their interactions with a broad phylogenetic range of mycorrhizal fungi indicate that common mycorrhizal networks are prevalent, particularly in forests, and result in net carbon transfer among diverse plants through shared mycorrhizal fungi. On the basis of the available scientific evidence, we propose a continuum of carbon transfer options within common mycorrhizal networks, and we discuss how knowledge on the biology of mycoheterotrophic plants can be instrumental for the study of mycorrhizal-mediated transfers between plants.
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Journal articleMwima R, Hui T-YJ, Kayondo JK, et al., 2024,
The population genetics of partial diapause, with applications to the aestivating malaria mosquito <i>Anopheles coluzzii</i>
, MOLECULAR ECOLOGY RESOURCES, Vol: 24, ISSN: 1755-098X -
Journal articlePereira HM, Martins IS, Rosa IMD, et al., 2024,
Global trends and scenarios for terrestrial biodiversity and ecosystem services from 1900 to 2050.
, Science, Vol: 384, Pages: 458-465Based on an extensive model intercomparison, we assessed trends in biodiversity and ecosystem services from historical reconstructions and future scenarios of land-use and climate change. During the 20th century, biodiversity declined globally by 2 to 11%, as estimated by a range of indicators. Provisioning ecosystem services increased several fold, and regulating services decreased moderately. Going forward, policies toward sustainability have the potential to slow biodiversity loss resulting from land-use change and the demand for provisioning services while reducing or reversing declines in regulating services. However, negative impacts on biodiversity due to climate change appear poised to increase, particularly in the higher-emissions scenarios. Our assessment identifies remaining modeling uncertainties but also robustly shows that renewed policy efforts are needed to meet the goals of the Convention on Biological Diversity.
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Journal articleBernard C, Liu Y, Larrouy-Maumus G, et al., 2024,
Altered serine metabolism promotes drug tolerance in <i>Mycobacterium abscessus</i> via a WhiB7-mediated adaptive stress response
, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, ISSN: 0066-4804 -
Journal articleGuerrero P, Perez-Carrasco R, 2024,
Choice of friction coefficient deeply affects tissue behaviour in stochastic epithelial vertex models
, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 379, ISSN: 0962-8436 -
Journal articleBlackford K, Kasoar M, Burton C, et al., 2024,
INFERNO-peat v1.0.0: a representation of northern high latitude peat fires in the JULES-INFERNO global fire model
, Geoscientific Model Development, Vol: 17, Pages: 3063-3079, ISSN: 1991-959XPeat fires in the northern high latitudes have the potential to burn vast amounts of carbon-rich organic soil, releasing large quantities of long-term stored carbon to the atmosphere. Due to anthropogenic activities and climate change, peat fires are increasing in frequency and intensity across the high latitudes. However, at present they are not explicitly included in most fire models. Here we detail the development of INFERNO-peat, the first parameterization of peat fires in the JULES-INFERNO (Joint UK Land Environment Simulator INteractive Fire and Emission algoRithm for Natural envirOnments) fire model. INFERNO-peat utilizes knowledge from lab and field-based studies on peat fire ignition and spread to be able to model peat burnt area, burn depth, and carbon emissions, based on data of the moisture content, inorganic content, bulk density, soil temperature, and water table depth of peat. INFERNO-peat improves the representation of burnt area in the high latitudes, with peat fires simulating on average an additional 0.305×106 km2 of burn area each year, emitting 224.10 Tg of carbon. Compared to Global Fire Emissions Database version 5 (GFED5), INFERNO-peat captures ∼ 20 % more burnt area, whereas INFERNO underestimated burning by 50 %. Additionally, INFERNO-peat substantially improves the representation of interannual variability in burnt area and subsequent carbon emissions across the high latitudes. The coefficient of variation in carbon emissions is increased from 0.071 in INFERNO to 0.127 in INFERNO-peat, an almost 80 % increase. Therefore, explicitly modelling peat fires shows a substantial improvement in the fire modelling capabilities of JULES-INFERNO, highlighting the importance of representing peatland systems in fire models.
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Journal articleWilliams J, Pettorelli N, Hartmann A, et al., 2024,
Decline of a distinct coral reef holobiont community under ocean acidification
, Microbiome, Vol: 12, ISSN: 2049-2618Background: Microbes play vital roles across coral reefs both in the environment and inside and upon macrobes (holobionts), where they support critical functions such as nutrition and immune system modulation. These roles highlight the potential ecosystem-level importance of microbes, yet most knowledge of microbial functions on reefs is derived from a small set of holobionts such as corals and sponges. Declining seawater pH - an important global coral reef stressor - can cause ecosystem-level change on coral reefs, providing an opportunity to study the role of microbes at this scale. We use an in situ experimental approach to test the hypothesis that under such ocean acidification (OA) known shifts among macrobe trophic and functional groups may drive a general ecosystem-level response extending across macrobes and microbes, leading to reduced distinctness between the benthic holobiont community microbiome and the environmental microbiome. Results: We test this hypothesis using genetic and chemical data from benthic coral reef community holobionts sampled across a pH gradient from CO2 seeps in Papua New Guinea. We find support for our hypothesis: under OA the microbiome and metabolome of the benthic holobiont community become less compositionally distinct from the sediment microbiome and metabolome, suggesting that benthic macrobe communities are colonized by environmental microbes to a higher degree under OA conditions. We also find a simplification and homogenisation of the benthic photosynthetic community, and an increased abundance of fleshy macroalgae, consistent with previously observed reef microbialisation. Conclusions: We demonstrate a novel structural shift in coral reefs involving macrobes and microbes: that the microbiome of the benthic holobiont community becomes less distinct from the sediment microbiome under OA. Our findings provide evidence that microbialisation and the disruption of macrobe trophic networks are interwoven general responses to envi
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Journal articleBradley R, Simon D, Spiga L, et al., 2024,
Laser desorption rapid evaporative ionization mass spectrometry (LD-REIMS) demonstrates a direct impact of hypochlorous acid stress on PQS-mediated quorum sensing in Pseudomonas aeruginosa
, mSystems, Vol: 9, ISSN: 2379-5077UNLABELLED: To establish infections in human hosts, Pseudomonas aeruginosa must overcome innate immune-generated oxidative stress, such as the hypochlorous acid (HOCl) produced by neutrophils. We set out to find specific biomarkers of oxidative stress through the development of a protocol for the metabolic profiling of P. aeruginosa cultures grown in the presence of different oxidants using a novel ionization technique for mass spectrometry, laser desorption rapid evaporative ionization mass spectrometry (LD-REIMS). We demonstrated the ability of LD-REIMS to classify samples as untreated or treated with a specific oxidant with 100% accuracy and identified a panel of 54 metabolites with significantly altered concentrations after exposure to one or more of the oxidants. Key metabolic changes were conserved in P. aeruginosa clinical strains isolated from patients with cystic fibrosis lung infections. These data demonstrated that HOCl stress impacted the Pseudomonas quinolone signal (PQS) quorum sensing system. Ten 2-alkyl-4-quinolones (AHQs) associated with the PQS system were significantly lower in concentration in HOCl-stressed P. aeruginosa cultures, including 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS), the most active signal molecule of the PQS system. The PQS system regulates the production of virulence factors, including pyocyanin and elastase, and their levels were markedly affected by HOCl stress. No pyocyanin was detectable and elastase concentrations were reduced by more than 75% in cultures grown with sub-lethal concentrations of HOCl, suggesting that this neutrophil-derived oxidant may disrupt the ability of P. aeruginosa to establish infections through interference with production of PQS-associated virulence factors. IMPORTANCE: This work demonstrates that a high-throughput ambient ionization mass spectrometry method can be used successfully to study a bacterial stress response. Its application to the opportunistic pathogen Pseudomonas aeruginosa led to the
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Journal articleMoulick D, Ghosh D, Gharde Y, et al., 2024,
An assessment of the impact of traditional rice cooking practice and eating habits on arsenic and iron transfer into the food chain of smallholders of Indo-Gangetic plain of South-Asia: Using AMMI and Monte-Carlo simulation model.
, Heliyon, Vol: 10, ISSN: 2405-8440The current study was designed to investigate the consequences of rice cooking and soaking of cooked rice (CR) with or without arsenic (As) contaminated water on As and Fe (iron) transfer to the human body along with associated health risk assessment using additive main-effects and multiplicative interaction (AMMI) and Monte Carlo Simulation model. In comparison to raw rice, As content in cooked rice (CR) and soaked cooked rice (SCR) enhanced significantly (at p < 0.05 level), regardless of rice cultivars and locations (at p < 0.05 level) due to the use of As-rich water for cooking and soaking purposes. Whereas As content in CR and SCR was reduced significantly due to the use of As-free water for cooking and soaking purposes. The use of As-free water (AFW) also enhanced the Fe content in CR. The overnight soaking of rice invariably enhanced the Fe content despite the use of As-contaminated water in SCR however, comparatively in lesser amount than As-free rice. In the studied area, due to consumption of As-rich CR and SCR children are more vulnerable to health hazards than adults. Consumption of SCR (prepared with AFW) could be an effective method to minimize As transmission and Fe enrichment among consumers.
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Journal articleDe A, Das A, Joardar M, et al., 2024,
Investigation of Groundwater Fluoride Dynamics in the Lower Gangetic Plain Including Natural Influences with Economic and Health Issues
, ACS ES and T Water, Vol: 4, Pages: 1356-1370The lower Gangetic Plain in West Bengal, India, has previously been reported to have groundwater fluoride (F-) contamination and its hazard; however, more information was needed about the precise location of contamination. The current study highlighted these knowledge gaps covering the toxicity of F- through groundwater by emphasizing the role of hydrogeochemical attributions in F- mobilization, people’s socioeconomic behavior, and assessing the possible health risks of the local population. Approximately, 10% of groundwater samples exceeded the recommended value of F- with a moderate contamination factor. The groundwater is highly saline (Na-Cl type) in nature. The intermediate zone between the area of ’rock dominance’ and ’precipitation dominance’ controlled the leaching of F- from host silicate minerals to groundwater. The saturation index established geogenic activity as the responsible factor and found silicate weathering mineral muscovite for F- leaching in groundwater. The average utility cost for 20 L of safe drinking water was US$ 7.58 per month from affordable households. Total hazard quotient (THQ) was observed maximum for infants and significant ingestion rate (IR), body weight (BW), and body surface area (SA) were the responsible factors for the studied age groups. Fluoride-safe drinking water supply strategies are a necessary step in the studied area.
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Journal articleZhang-Zheng H, Adu-Bredu S, Duah-Gyamfi A, et al., 2024,
Contrasting carbon cycle along tropical forest aridity gradients in West Africa and Amazonia
, Nature Communications, Vol: 15, ISSN: 2041-1723Tropical forests cover large areas of equatorial Africa and play a substantial role in the global carbon cycle. However, there has been a lack of biometric measurements to understand the forests’ gross and net primary productivity (GPP, NPP) and their allocation. Here we present a detailed field assessment of the carbon budget of multiple forest sites in Africa, by monitoring 14 one-hectare plots along an aridity gradient in Ghana, West Africa. When compared with an equivalent aridity gradient in Amazonia, the studied West African forests generally had higher productivity and lower carbon use efficiency (CUE). The West African aridity gradient consistently shows the highest NPP, CUE, GPP, and autotrophic respiration at a medium-aridity site, Bobiri. Notably, NPP and GPP of the site are the highest yet reported anywhere for intact forests. Widely used data products substantially underestimate productivity when compared to biometric measurements in Amazonia and Africa. Our analysis suggests that the high productivity of the African forests is linked to their large GPP allocation to canopy and semi-deciduous characteristics.
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Journal articleOgwang R, Murugu L, Nailain I, et al., 2024,
Bi-isotype immunoglobulins enhance antibody-mediated neutrophil activity against Plasmodium falciparum parasites
, Frontiers in Immunology, Vol: 15, ISSN: 1664-3224Background: Malaria remains a major global health priority, and monoclonal antibodies (mAbs) are emerging as potential new tools to support efforts to control the disease. Recent data suggest that Fc-dependent mechanisms of immunity are important mediators of protection against the blood stages of the infection, but few studies have investigated this in the context of mAbs. We aimed to isolate mAbs agnostic to cognate antigens that target whole merozoites and simultaneously induce potent neutrophil activity measured by the level of reactive oxygen species (ROS) production using an antibody-dependent respiratory burst (ADRB) assay.Methods: We used samples from semi-immune adults living in coastal Kenya to isolate mAbs that induce merozoite-specific ADRB activity. We then tested whether modifying the expressed IgG1 isotype to an IgG–IgA Fc region chimera would enhance the level of ADRB activity.Results: We isolated a panel of nine mAbs with specificity to whole merozoites. mAb J31 induced ADRB activity in a dose-dependent fashion. Compared to IgG1, our modified antibody IgG–IgA bi-isotype induced higher ADRB activity across all concentrations tested. Further, we observed a negative hook effect at high IgG1 mAb concentrations (i.e., >200 µg/mL), but this was reversed by Fc modification. We identified MSP3.5 as the potential cognate target of mAb J31.Conclusions: We demonstrate an approach to engineer mAbs with enhanced ADRB potency against blood-stage parasites.
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Journal articleSmith TP, Clegg T, Ransome E, et al., 2024,
High-throughput characterization of bacterial responses to complex mixtures of chemical pollutants
, Nature Microbiology, Vol: 9, Pages: 938-948, ISSN: 2058-5276Our understanding of how microbes respond to micropollutants, such as pesticides, is almost wholly based on single-species responses to individual chemicals. However, in natural environments, microbes experience multiple pollutants simultaneously. Here we perform a matrix of multi-stressor experiments by assaying the growth of model and non-model strains of bacteria in all 255 combinations of 8 chemical stressors (antibiotics, herbicides, fungicides and pesticides). We found that bacterial strains responded in different ways to stressor mixtures, which could not be predicted simply from their phylogenetic relatedness. Increasingly complex chemical mixtures were both more likely to negatively impact bacterial growth in monoculture and more likely to reveal net interactive effects. A mixed co-culture of strains proved more resilient to increasingly complex mixtures and revealed fewer interactions in the growth response. These results show predictability in microbial population responses to chemical stressors and could increase the utility of next-generation eco-toxicological assays.
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Journal articleStiller J, Feng S, Chowdhury A-A, et al., 2024,
Complexity of avian evolution revealed by family-level genomes
, NATURE, ISSN: 0028-0836 -
Journal articleKabasakal BV, Cotton CAR, Murray JW, 2024,
Dynamic lid domain of Chloroflexus aurantiacus Malonyl-CoA reductase controls the reaction.
, Biochimie, Vol: 219, Pages: 12-20, ISSN: 0300-9084Malonyl-Coenzyme A Reductase (MCR) in Chloroflexus aurantiacus, a characteristic enzyme of the 3-hydroxypropionate (3-HP) cycle, catalyses the reduction of malonyl-CoA to 3-HP. MCR is a bi-functional enzyme; in the first step, malonyl-CoA is reduced to the free intermediate malonate semialdehyde by the C-terminal region of MCR, and this is further reduced to 3-HP by the N-terminal region of MCR. Here we present the crystal structures of both N-terminal and C-terminal regions of the MCR from C. aurantiacus. A catalytic mechanism is suggested by ligand and substrate bound structures, and structural and kinetic studies of MCR variants. Both MCR structures reveal one catalytic, and one non-catalytic SDR (short chain dehydrogenase/reductase) domain. C-terminal MCR has a lid domain which undergoes a conformational change and controls the reaction. In the proposed mechanism of the C-terminal MCR, the conversion of malonyl-CoA to malonate semialdehyde is based on the reduction of malonyl-CoA by NADPH, followed by the decomposition of the hemithioacetal to produce malonate semialdehyde and coenzyme A. Conserved arginines, Arg734 and Arg773 are proposed to play key roles in the mechanism and conserved Ser719, and Tyr737 are other essential residues forming an oxyanion hole for the substrate intermediates.
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Journal articleGriffiths D, Anderson M, Richardson K, et al., 2024,
Cyclic Ion Mobility for Hydrogen/Deuterium Exchange-Mass Spectrometry Applications
, ANALYTICAL CHEMISTRY, ISSN: 0003-2700 -
Journal articleFung YY, Carbone C, Scott-Gatty K, et al., 2024,
Habitat suitability as an indicator of urbanisation potential in four UK mammals
, MAMMAL REVIEW, Vol: 54, Pages: 105-120, ISSN: 0305-1838
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