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Journal articleZhang H, Wang H, Wright IJ, et al., 2025,
Thermal acclimation of stem respiration implies a weaker carbon-climate feedback
, Science, ISSN: 0036-8075 -
Journal articleSauthof L, Szczepek M, Schmidt A, et al., 2025,
Serial-femtosecond crystallography reveals how a phytochrome variant couples chromophore and protein structural changes
, SCIENCE ADVANCES, Vol: 11- Cite
- Citations: 1
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Journal articleYu X, Nollet M, Franks N, et al., 2025,
Sleep and the recovery from stress
, Neuron, ISSN: 0896-6273The relationship between stress and sleep is multifaceted, with stress capable of both disrupting and promoting sleep depending on the nature, intensity, and duration of the stressor. While stress commonly leads to sleep fragmentation and arousal in both humans and animals, certain selective stressors, such as immune challenges and psychosocial stress, promote sleep in rodent models. Specific neural circuits, such as those involving the ventral tegmental area and lateral habenula, mediate this stress-induced sleep. Post-stress sleep may facilitate recovery, reduce anxiety, and enhance stress resilience, but the extent to which sleep versus wakefulness post-stress aids long-term adaptation is unclear. Both human and animal studies highlight a bidirectional relationship, where stress-induced changes in sleep architecture may have adaptive or maladaptive consequences. Here, we propose that post-stress sleep contributes to resilience and discuss potential mechanisms underlying this process. A deeper understanding of these pathways may provide new strategies for enhancing stress recovery and improving mental health outcomes.
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Journal articlePringle S, Dallimer M, Goddard MA, et al., 2025,
Opportunities and challenges for monitoring terrestrial biodiversity in the robotics age
, Nature Ecology & Evolution, ISSN: 2397-334XWith biodiversity loss escalating globally, a step change is needed in our capacity to accurately monitor species populations across ecosystems. Robotic and autonomous systems (RAS) offer technological solutions that may substantially advance terrestrial biodiversity monitoring, but this potential is yet to be considered systematically. We used a modified Delphi technique to synthesize knowledge from 98 biodiversity experts and 31 RAS experts, who identified the major methodological barriers that currently hinder monitoring, and explored the opportunities and challenges that RAS offer in overcoming these barriers. Biodiversity experts identified four barrier categories: site access, species and individual identification, data handling and storage, and power and network availability. Robotics experts highlighted technologies that could overcome these barriers and identified the developments needed to facilitate RAS-based autonomous biodiversity monitoring. Some existing RAS could be optimized relatively easily to survey species but would require development to be suitable for monitoring of more ‘difficult’ taxa and robust enough to work under uncontrolled conditions within ecosystems. Other nascent technologies (for instance, new sensors and biodegradable robots) need accelerated research. Overall, it was felt that RAS could lead to major progress in monitoring of terrestrial biodiversity by supplementing rather than supplanting existing methods. Transdisciplinarity needs to be fostered between biodiversity and RAS experts so that future ideas and technologies can be codeveloped effectively.
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ReportMoustafa N, Saenz Cavazos P, Beath H, et al., 2025,
Destination Net-Zero: what is your best path? Insights for decision-makers navigating the low carbon transition
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Journal articleMcArthur HCW, Bajur AT, Iliopoulou M, et al., 2025,
Antigen mobility regulates the dynamics and precision of antigen capture in the B cell immune synapse
, Proceedings of the National Academy of Sciences of USA, Vol: 122, ISSN: 0027-8424B cells discriminate antigens in immune synapses by capturing them from antigen-presenting cells (APCs). This discrimination relies on the application of mechanical force to B cell receptor (BCR)-antigen bonds, allowing B cells to selectively disrupt low-affinity interactions while internalizing high-affinity antigens. Using DNA-based tension sensors combined with high-resolution imaging, we demonstrate that the magnitude, location, and timing of forces within the immune synapse are influenced by the fluidity of the antigen-presenting membrane. Transitioning antigens from a high-mobility to a low-mobility substrate significantly increases the probability and speed of antigen extraction while also improving affinity discrimination. This shift in antigen mobility also reshapes the synapse architecture, altering spatial patterns of antigen uptake. Despite these adaptations, B cells maintain consistent levels of proximal and downstream signaling pathway activation regardless of antigen mobility. They also efficiently transport internalized antigens to major histocompatibility complex class II (MHCII)-positive compartments for processing. These results demonstrate that B cells mount effective responses to antigens across diverse physical environments, though the characteristics of that environment may influence the speed and accuracy of B cell adaptation during an immune response.
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Journal articleAlonso A, Kirkegaard JB, Endres RG, 2025,
Persistent pseudopod splitting is an effective chemotaxis strategy in shallow gradients
, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 122, ISSN: 0027-8424- Cite
- Citations: 1
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Journal articleYesilyurt-Dirican ZE, Qi C, Wang Y-C, et al., 2025,
SGLT2 inhibitors as a novel senotherapeutic approach
, NPJ AGING, Vol: 11- Cite
- Citations: 3
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Conference paperXu V, Barritt J, Bubeck D, et al., 2025,
Countdown to Package: Molecular Insights into the Rep-mediated Adenoassociated-virus Packaging Machinery
, 28th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), Publisher: CELL PRESS, ISSN: 1525-0016 -
Journal articleRice AJ, Sword TT, Chengan K, et al., 2025,
Cell-free synthetic biology for natural product biosynthesis and discovery
, CHEMICAL SOCIETY REVIEWS, Vol: 54, Pages: 4314-4352, ISSN: 0306-0012- Cite
- Citations: 7
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Journal articleLieb ZE, Meijaard E, Brodie JF, et al., 2025,
Mapping multiple wild pig species’ population dynamics in southeast asia during the african swine fever outbreak (2018–2024)
, Conservation Letters, Vol: 18, ISSN: 1755-263XThe 2018 arrival of African swine fever (ASF) in China was followed by reports of wild pig deaths across most countries in Southeast Asia. However, the magnitude and duration of population-level impacts of ASF on wild pig species remain unclear. To elucidate the spatiotemporal spread of ASF in the region for native pig species, we gathered qualitative information on wild pig population dynamics in Southeast Asia between 2018 and 2024 from 88 expert elicitation questionnaires representing sites in 11 countries. Peak reported population declines occurred in 2021 and 2022, with more than half of respondents reporting declining wild pig populations, far higher than in earlier years. The reported declines waned to 44.23% in 2024, whereas simultaneously, the number of populations reported to be “increasing” increased from 11.3%–13.2% in 2019–2022 to 28.9% in 2024. These reports suggest that the ASF outbreak may have peaked for wild boars and bearded pigs in mainland Southeast Asia, Borneo, and Sumatra, with some subsequent recovery. However, the disease is still expanding into the ranges of island endemic species, such as new reports for the Sulawesi warty pig (Sus celebensis) in September of 2024. Island endemics remain particularly vulnerable to extinction from ASF and require urgent monitoring and conservation action.
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Journal articleKim TD, Pretorius D, Murray JW, et al., 2025,
Exploring the structural diversity and evolution of the D1 subunit of photosystem II using AlphaFold and Foldtree
, Physiologia Plantarum, Vol: 177, ISSN: 0031-9317Although our knowledge of photosystem II has expanded to include time-resolved atomic details, the diversity of experimental structures of the enzyme remains limited. Recent advances in protein structure prediction with AlphaFold offer a promising approach to fill this gap in structural diversity in non-model systems. This study used AlphaFold to predict the structures of the D1 protein, the core subunit of photosystem II, across a broad range of photosynthetic organisms. The prediction produced high-confidence structures, and structural alignment analyses highlighted conserved regions across the different D1 groups, which were in line with high pLDDT scoring regions. In contrast, varying pLDDT in the DE loop and terminal regions appears to correlate with different degrees of structural flexibility or disorder. Subsequent structural phylogenetic analysis using Foldtree provided a tree that is in good agreement with previous sequence-based studies. Moreover, the phylogeny supports a parsimonious scenario in which far-red D1 and D1INT evolved from an ancestral form of G4 D1. This work demonstrates the potential of AlphaFold and Foldtree to study the molecular evolution of photosynthesis.
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Journal articleSmith TP, Hope R, Bell T, 2025,
Phylogenetic clustering of microbial communities as a biomarker for chemical pollution
, FEMS Microbiology Ecology, Vol: 101, ISSN: 0168-6496Microbial communities play a critical role in ecosystem functioning and offer promising potential as bioindicators of chemical pollution in aquatic environments. Here we examine the responses of both bacterial isolates and microbial communities to a range of pollutants, focusing on the phylogenetic predictability of their responses. We tested the growth inhibition of environmental bacterial isolates by 168 agricultural pollutants recently shown to have off-purpose antimicrobial activity in human gut bacteria. We also tested the growth responses of whole microbial communities to the same chemical pollutants and quantified changes in the composition of select communities, to link compositional changes to functioning. We found that bacterial isolates exhibited a strong phylogenetic signal in their growth responses, with closely related taxa responding similarly to chemical stress. In microbial communities, pollutants that significantly impacted isolates also reduced community diversity and growth, causing shifts in community structure toward increased phylogenetic clustering, suggesting environmental filtering. The mean phylogenetic distance effectively captured these shifts, indicating its potential as a simple metric for monitoring pollution. Our findings highlight the predictability of microbial responses to pollution and suggest that microbial-based bioindicators, coupled with rapid sequencing technologies, could transform environmental monitoring.
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Journal articleHordley LA, Powney GD, Brereton T, et al., 2025,
Disentangling how climate and dispersal drive temporal trends in synchronous population dynamics
, Ecology and Evolution, Vol: 15, ISSN: 2045-7758Spatially synchronised population dynamics are driven by a combination of shared environmental conditions among sites and the movements of individuals between sites. Untangling the drivers of population synchrony requires investigation of how populations are correlated across space and time in relation to climate and mobility-related attributes. Here, we use species survey data from over four decades to investigate average levels and temporal trends in population synchrony for 58 British bird and butterfly species. We first show that population synchrony is significantly associated with synchrony in seasonal climatic variables. After accounting for spatiotemporal climatic patterns, we determine whether temporal trends in population synchrony are shaped by mobility-related attributes. We test this through an interspecies comparison using three variables correlated with mobility: biotope specialism, estimated species mobility, and local abundance change, which is known to affect emigration rate. We find that temporal trends in population synchrony are most marked for generalist butterfly species, butterflies with high estimated mobility, and butterflies that had changed in their mean abundance. For birds, we find changes in population synchrony are associated with specialist bird species and those that increased in abundance over time. Our results reveal a widespread effect of mobility attributes and abundance patterns on population synchrony over time, suggesting that variation in dispersal is a key factor determining the extent to which population dynamics are synchronised.
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Journal articleDarras KFA, Rountree RA, Van Wilgenburg SL, et al., 2025,
Worldwide Soundscapes: A Synthesis of Passive Acoustic Monitoring Across Realms
, Global Ecology and Biogeography, Vol: 34, ISSN: 1466-822XAim: The urgency for remote, reliable and scalable biodiversity monitoring amidst mounting human pressures on ecosystems has sparked worldwide interest in Passive Acoustic Monitoring (PAM), which can track life underwater and on land. However, we lack a unified methodology to report this sampling effort and a comprehensive overview of PAM coverage to gauge its potential as a global research and monitoring tool. To address this gap, we created the Worldwide Soundscapes project, a collaborative network and growing database comprising metadata from 416 datasets across all realms (terrestrial, marine, freshwater and subterranean). Location: Worldwide, 12,343 sites, all ecosystem types. Time Period: 1991 to present. Major Taxa Studied: All soniferous taxa. Methods: We synthesise sampling coverage across spatial, temporal and ecological scales using metadata describing sampling locations, deployment schedules, focal taxa and audio recording parameters. We explore global trends in biological, anthropogenic and geophysical sounds based on 168 selected recordings from 12 ecosystems across all realms. Results: Terrestrial sampling is spatially denser (46 sites per million square kilometre—Mkm<sup>2</sup>) than aquatic sampling (0.3 and 1.8 sites/Mkm<sup>2</sup> in oceans and fresh water) with only two subterranean datasets. Although diel and lunar cycles are well sampled across realms, only marine datasets (55%) comprehensively sample all seasons. Across the 12 ecosystems selected for exploring global acoustic trends, biological sounds showed contrasting diel patterns across ecosystems, declined with distance from the Equator, and were negatively correlated with anthropogenic sounds. Main Conclusions: PAM can inform macroecological studies as well as global conservation and phenology syntheses, but representation can be improved by expanding terrestrial taxonomic scope, sampling coverage in the high seas and subterranean ecosystems, and spatio-te
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Journal articleDodds IL, Watts EC, Schuster M, et al., 2025,
Immunity gene silencing increases transient protein expression in Nicotiana benthamiana
, Plant Biotechnology Journal, Vol: 23, Pages: 1768-1770, ISSN: 1467-7644 -
Journal articleGiblin SP, McKenna S, Matthews S, et al., 2025,
The N-terminal ELR+ motif of the neutrophil attractant CXCL8 confers susceptibility to degradation by the Group A Streptococcal protease, SpyCEP
, Journal of Biological Chemistry, Vol: 301, ISSN: 0021-9258Streptococcus pyogenes (Group A Streptococcus or GAS) is a major human pathogen for which an effective vaccine is highly desirable. Invasive S. pyogenes strains evade the host immune response in part by producing a cell envelope protease, SpyCEP. This neutralizes chemokines containing an N-terminal Glu-Leu-Arg motif (ELR+ chemokines) by cleavage at a distal C-terminal site within the chemokine. SpyCEP is a component of several S. pyogenes vaccines, yet the molecular determinants underlying substrate selectivity are poorly understood. We hypothesized that chemokine recognition and cleavage is a multistep process involving distinct domains of both substrate and enzyme. We generated a panel of recombinant CXCL8 variants where domains of the chemokine were exchanged or mutated. Chemokine degradation by SpyCEP was assessed by SDS-PAGE, Western blot, and ELISA. Extension of the CXCL8 N-terminus was found to inhibit chemokine cleavage. Reciprocal exchanges of the N-termini of CXCL8 with that of the ELR- chemokine CXCL4 resulted in the generation of loss of function and gain of function substrates. This suggested a key role for the ELR motif in substrate recognition, which was supported directly by alanine substitution of the ELR motif of CXCL8, impairing the parameters, KM, Vmax, and Kcat in kinetic assays with SpyCEP. Collectively, our findings identify the N-terminal ELR motif as a major determinant for recognition by SpyCEP and expose a vulnerability in the mechanism by which the protease recognises its substrates. This likely presents potential avenues for therapeutic intervention via targeted vaccine design and small molecule inhibition.
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Journal articleNingthoujam R, Bloomfield KJ, Crawley MJ, et al., 2025,
Hyperspectral sensing of abovegroundbiomass and species diversity in a longrunninggrassland experiment
, Ecological Informatics, Vol: 86, ISSN: 1574-9541Vegetation properties can be assessed through analysis of canopy reflectance spectra. Early techniques relied onsimple two-band vegetation indices (VIs) that exploit leaf reflectance properties at key wavelengths. As thetechnology matures it is now possible to gather and test hyperspectral data. Little evidence exists on howdifferent management regimes, such as nutrient addition, might affect hyperspectral reflectance and thus influence derived estimates of plant diversity and productivity. At a grassland experiment in southern England, we used a portable spectroradiometer to sample 96 plots exposed to multifactorial treatments combining herbivory, plant competition, soil pH and fertility. Our objective was to compare the predictive performance of popular two-band VIs with a multivariate partial least square regression (PLSR) model that uses all available wavelengths. We found that the PLSR models showed higher predictive power than the best performing VIs – that was especially true for our measure of species diversity (R2cv = 0.36 compared with a Pearson correlation of 0.21). The predictive power for our PLSR model of biomass (R2cv = 0.54) compares favourably with values reported in earlier grassland studies. These results confirm that hyperspectral measurement combined with multivariate regression techniques is a promising approach for monitoring grassland properties. There is evidence of particular benefit in capturing narrow bands associated with the red edge region of the spectrum (700–750 nm). Remotely sensed hyperspectral images at a fine spatial scale offer the prospect for matching with sampling units as small as the 2 × 2 m nutrient subplots measured here.
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Journal articleDias Fernandes L, Hintzen R, Thompson S, et al., 2025,
Species richness and speciation rates for all terrestrial animals emerge from a synthesis of ecological theories
, Systematic Biology, Vol: 74, Pages: 469-482, ISSN: 1063-5157The total number of species on earth and the rate at which new species are created are fundamental questions for ecology, evolution and conservation. These questions have typically been approached separately, despite their obvious interconnection. In this studywe approach both questions in conjunction, for all terrestrial animals. To do this, we combine two previously unconnected bodies of theory: general ecosystem models and individual based ecological neutral theory. General ecosystem models provide us with estimated numbers of individual organisms, separated by functional group and body size. Neutral theory, applied within a guild of functionally similar individuals, connects speciesrichness, speciation rate and number of individual organisms. In combination, for terrestrial endotherms where species numbers are known, they provide us with estimates for speciation rates as a function of body size and diet class. Extrapolating the same rates to guilds of ectotherms enables us to estimate the species richness of those groups, including species yet to be described. We find that speciation rates per species per millionyears decrease with increasing body size. Rates are also higher for carnivores compared to omnivores or herbivores of the same body size. Our estimate for the total number of terrestrial species of animals is in the range 1.03 − 2.92 million species, a value consistentwith estimates from previous studies, despite having used a fundamentally new approach. Perhaps what is most remarkable about these results is that they have been obtained using only limited data from larger endotherms and their speciation rates, with the predictive process being based on mechanistic theory. This work illustrates the potential of a new approach to classic eco-evolutionary questions, while also adding weight to existing predictions. As we now face an era of dramatic biological change, new methods will be needed to mechanistically model global biodiversity at the specie
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Journal articleZhao L, Galloway J, Ledingham J, et al., 2025,
Psychological distress over 12 months post-diagnosis in an early inflammatory arthritis cohort
, Rheumatology, Vol: 64, Pages: 2469-2478, ISSN: 1462-0324<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Objectives</jats:title> <jats:p>People with inflammatory arthritis (IA) experience worsened mental wellbeing alongside disease progression. Using the National Early Inflammatory Arthritis Audit (NEIAA), we assessed trends in psychological distress during the 12 months following IA diagnosis, mapping these against clinical outcomes to identify associations.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>This is a prospective study of people recruited to NEIAA receiving an IA diagnosis and completing the baseline patient survey. Patient-reported outcomes (PROs) at baseline, 3 months and 12 months were collected, including psychological distress [assessed using Patient Health Questionnaire Anxiety and Depression Screener (PHQ4ADS)]. Mixed effects linear regression models estimated associations between predictor variables with psychological distress at baseline and over time.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Of 6873 eligible patients, 3451 (50.2%) showed psychological distress at baseline. Of those completing follow-ups, 30.0% and 24.1% were distressed at 3 months and 12 months, respectively. Higher psychological distress at diagnosis was more commonly reported by younger, female and non-White patients. Clinical factors, including higher counts of comorbidities, prior depression and higher disease activity at diagnosis were associated with higher distress. Higher distress at baseline was associated with poorer outcomes over time in quality of life, disability, work performance, disease activity, as well as reduced likelihood of achieving good treatme
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Journal articleChavez EA, Adkins J, Waring BG, et al., 2025,
Herbivory in a low Arctic wetland alters intraspecific plant root traits with consequences for carbon and nitrogen cycling
, JOURNAL OF ECOLOGY, Vol: 113, Pages: 1225-1238, ISSN: 0022-0477 -
Journal articleNewbold T, Kerr J, Soroye P, et al., 2025,
Bumble Bee Probability of Occurrence Responds to Interactions Between Local and Landscape Land Use, Climatic Niche Properties and Climate Change
, ECOLOGY LETTERS, Vol: 28, ISSN: 1461-023X -
Journal articleBenites P, Garcia-Bautista A, Bautista-Briseno N, et al., 2025,
Drivers of Insect Diversity and Community Turnover in Protected Tropical Deciduous Forests of Mexico
, ENVIRONMENTAL DNA, Vol: 7, ISSN: 2637-4943 -
Journal articleVlachou D, Ukegbu CV, Mohamed M, et al., 2025,
Nanobody-mediated targeting of Plasmodium falciparum PfPIMMS43 can block malaria transmission in mosquitoes
, Communications Biology, Vol: 8, ISSN: 2399-3642The transition from ookinete to oocyst is a critical step in the Plasmodium falciparum lifecycle and an important target for malaria transmission-blocking strategies. PfPIMMS43, a surface protein of P. falciparum ookinetes and sporozoites, is critical for this transition and aids the parasite in evading mosquito immune responses. Previous studies demonstrated that polyclonal PfPIMMS43 antibodies reduced P. falciparum infection in Anopheles mosquitoes. Here, building on these findings, we have developed high-affinity single-domain VHH antibodies (nanobodies) derived from llama heavy-chain-only antibodies. We have shown that these nanobodies bind both recombinant and endogenous PfPIMMS43 produced by P. falciparum ookinetes in the mosquito midgut. Importantly, they significantly reduce infection intensity and prevalence of laboratory and field strains of P. falciparum in An. coluzzii and An. gambiae, respectively. Epitope mapping has revealed that the nanobodies target conserved regions in the second half of PfPIMMS43, with homology modelling confirming epitope accessibility. These findings establish PfPIMMS43 as a promising transmission-blocking target. To enhance malaria control and elimination efforts, we propose an innovative strategy in which genetically modified mosquitoes express PfPIMMS43-specific nanobodies in their midguts and spread this trait in wild mosquito populations via gene drive technology.
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Journal articleGao F, Ye F, Buck M, et al., 2025,
Subunit specialization in AAA+ proteins and substrate unfolding during transcription complex remodeling
, Proceedings of the National Academy of Sciences, Vol: 122, ISSN: 0027-8424Bacterial RNA polymerase (RNAP) is a multisubunit enzyme that copies DNA into RNA in a process known as transcription. Bacteria use σ factors to recruit RNAP to promoter regions of genes that need to be transcribed, with 60% bacteria containing at least one specialized σ factor, σ54. σ54 recruits RNAP to promoters of genes associated with stress responses and forms a stable closed complex that does not spontaneously isomerize to the open state where promoter DNA is melted out and competent for transcription. The σ54-mediated open complex formation requires specific AAA+ proteins (ATPases Associated with diverse cellular Activities) known as bacterial enhancer-binding proteins (bEBPs). We have now obtained structures of new intermediate states of bEBP-bound complexes during transcription initiation, which elucidate the mechanism of DNA melting driven by ATPase activity of bEBPs and suggest a mechanistic model that couples the Adenosine triphosphate (ATP) hydrolysis cycle within the bEBP hexamer with σ54 unfolding. Our data reveal that bEBP forms a nonplanar hexamer with the hydrolysis-ready subunit located at the furthest/highest point of the spiral hexamer relative to the RNAP. ATP hydrolysis induces conformational changes in bEBP that drives a vectoral transiting of the regulatory N terminus of σ54 into the bEBP hexamer central pore causing the partial unfolding of σ54, while forming specific bEBP contacts with promoter DNA. Furthermore, our data suggest a mechanism of the bEBP AAA+ protein that is distinct from the hand-over-hand mechanism proposed for many other AAA+ proteins, highlighting the versatile mechanisms utilized by the large protein family.
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Journal articleVerkuijl SAN, Corsano GD, Capriotti P, et al., 2025,
A suppression-modification gene drive for malaria control targeting the ultra-conserved RNA gene mir-184
, Nature Communications, Vol: 16, ISSN: 2041-1723Gene drive technology presents a promising approach to controlling malaria vector populations. Suppression drives are intended to disrupt essential mosquito genes whereas modification drives aim to reduce the individual vectorial capacity of mosquitoes. Here we present a highly efficient homing gene drive in the African malaria vector Anopheles gambiae that targets the microRNA gene mir-184 and combines suppression with modification. Homozygous gene drive (miR-184D) individuals incur significant fitness costs, including high mortality following a blood meal, that curtail their propensity for malaria transmission. We attribute this to a role of miR-184 in regulating solute transport in the mosquito gut. However, females remain fully fertile, and pure-breeding miR-184D populations suitable for large-scale releases can be reared under laboratory conditions. Cage invasion experiments show that miR-184D can spread to fixation thereby reducing population fitness, while being able to propagate a separate antimalarial effector gene at the same time. Modelling indicates that the miR-184D drive integrates aspects of population suppression and population replacement strategies into a candidate strain that should be evaluated further as a tool for malaria eradication.
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Journal articleOqua AI, Chao K, El Eid L, et al., 2025,
Molecular mapping and functional validation of GLP-1R cholesterol binding sites in pancreatic beta cells
, eLife, Vol: 13<jats:p>G protein-coupled receptors (GPCRs) are integral membrane proteins which closely interact with their plasma membrane lipid microenvironment. Cholesterol is a lipid enriched at the plasma membrane with pivotal roles in the control of membrane fluidity and maintenance of membrane microarchitecture, directly impacting on GPCR stability, dynamics, and function. Cholesterol extraction from pancreatic beta cells has previously been shown to disrupt the internalisation, clustering, and cAMP responses of the glucagon-like peptide-1 receptor (GLP-1R), a class B1 GPCR with key roles in the control of blood glucose levels via the potentiation of insulin secretion in beta cells and weight reduction via the modulation of brain appetite control centres. Here, we unveil the detrimental effect of a high cholesterol diet on GLP-1R-dependent glucoregulation in vivo, and the improvement in GLP-1R function that a reduction in cholesterol synthesis using simvastatin exerts in pancreatic islets. We next identify and map sites of cholesterol high occupancy and residence time on active <jats:italic>vs</jats:italic> inactive GLP-1Rs using coarse-grained molecular dynamics (cgMD) simulations, followed by a screen of key residues selected from these sites and detailed analyses of the effects of mutating one of these, Val229, to alanine on GLP-1R-cholesterol interactions, plasma membrane behaviours, clustering, trafficking and signalling in INS-1 832/3 rat pancreatic beta cells and primary mouse islets, unveiling an improved insulin secretion profile for the V229A mutant receptor. This study (1) highlights the role of cholesterol in regulating GLP-1R responses in vivo; (2) provides a detailed map of GLP-1R - cholesterol binding sites in model membranes; (3) validates their functional relevance in beta cells; and (4) highlights their potential as locations for the rational design of novel allosteric modulators with the capacity to fine-tune GLP-1R responses.</jats:p
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Journal articleOqua AI, Chao K, El Eid L, et al., 2025,
Molecular mapping and functional validation of GLP-1R cholesterol binding sites in pancreatic beta cells
, eLife, Vol: 13<jats:p>G protein-coupled receptors (GPCRs) are integral membrane proteins which closely interact with their plasma membrane lipid microenvironment. Cholesterol is a lipid enriched at the plasma membrane with pivotal roles in the control of membrane fluidity and maintenance of membrane microarchitecture, directly impacting on GPCR stability, dynamics, and function. Cholesterol extraction from pancreatic beta cells has previously been shown to disrupt the internalisation, clustering, and cAMP responses of the glucagon-like peptide-1 receptor (GLP-1R), a class B1 GPCR with key roles in the control of blood glucose levels via the potentiation of insulin secretion in beta cells and weight reduction via the modulation of brain appetite control centres. Here, we unveil the detrimental effect of a high cholesterol diet on GLP-1R-dependent glucoregulation in vivo, and the improvement in GLP-1R function that a reduction in cholesterol synthesis using simvastatin exerts in pancreatic islets. We next identify and map sites of cholesterol high occupancy and residence time on active <jats:italic>vs</jats:italic> inactive GLP-1Rs using coarse-grained molecular dynamics (cgMD) simulations, followed by a screen of key residues selected from these sites and detailed analyses of the effects of mutating one of these, Val229, to alanine on GLP-1R-cholesterol interactions, plasma membrane behaviours, clustering, trafficking and signalling in INS-1 832/3 rat pancreatic beta cells and primary mouse islets, unveiling an improved insulin secretion profile for the V229A mutant receptor. This study (1) highlights the role of cholesterol in regulating GLP-1R responses in vivo; (2) provides a detailed map of GLP-1R - cholesterol binding sites in model membranes; (3) validates their functional relevance in beta cells; and (4) highlights their potential as locations for the rational design of novel allosteric modulators with the capacity to fine-tune GLP-1R responses.</jats:p
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Journal articleIshimoto N, Wong JLC, He S, et al., 2025,
Cryo-EM structure of the conjugation H-pilus reveals the cyclic nature of the TrhA pilin
, Proceedings of the National Academy of Sciences, Vol: 122, ISSN: 0027-8424Conjugation, the major driver of the spread of antimicrobial resistance genes, relies on a conjugation pilus for DNA transfer. Conjugative pili, such as the F-pilus, are dynamic tubular structures, composed of a polymerized pilin, that mediate the initial donor–recipient interactions, a process known as mating pair formation (MPF). IncH are low-copy-number plasmids, traditionally considered broad host range, which are found in bacteria infecting both humans and animals. The reference IncHI1 plasmid R27, isolated from Salmonella enterica serovar Typhi, encodes the conjugative H-pilus subunit TrhA containing 74 residues after cleavage of the signal sequence. Here, we show that the H-pilus forms long filamentous structures that mediate MPF and describe its cryoelectron-microscopic (cryo-EM) structure at 2.2 Å resolution. Like the F pilus, the H-pilin subunits form helical assemblies with phospholipid molecules at a stoichiometric ratio of 1:1. While there were previous reports that the T-pilus from Agrobacterium tumefaciens was composed of cyclic subunits, three recent cryo-EM structures of the T-pilus found no such cyclization. Here, we report that the H-pilin is cyclic, with a covalent bond connecting the peptide backbone between the N and C termini. Both the cryo-EM map and mass spectrometry revealed cleavage of the last five residues of the pilin, followed by cyclization via condensation of the amine and carboxyl residues. Mutagenesis experiments revealed that loss of cyclization abolished pilus biogenesis and efficient plasmid transfer. The cyclic nature of the pilin could stabilize the pilus and may explain the high incidence of IncH plasmid dissemination.
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Journal articleYang J, Yang C, Lin H-W, et al., 2025,
Elevational constraints on flight efficiency shape global gradients in avian wing morphology
, Current Biology, Vol: 35, Pages: 1890-1900.e5, ISSN: 0960-9822Wings with an elongated shape or larger surface area are associated with increased flight efficiency in a wide range of animals from insects to birds.1,2,3,4 Inter- and intra-specific variation in these attributes of wing shape is determined by a range of factors—including foraging ecology, migration, and climatic seasonality5,6,7,8—all of which may drive latitudinal gradients in wing morphology.9,10 A separate hypothesis predicts that wing shape should also follow an elevational gradient5,11 because air density declines with altitude,12 altering the aerodynamics of flight and driving the evolution of more efficient wings in high-elevation species to compensate for reduced lift.13,14,15 Although previous analyses have shown a tendency for longer or larger wings at higher elevations, at least locally,16,17,18,19,20 it is difficult to rule out a range of alternative explanations since we currently lack a global synthesis of elevational gradients in wing shape for any taxonomic group. In this study, we use phylogenetic models to explore elevational effects on metrics of wing morphology linked to aerodynamic function in 9,982 bird species while simultaneously controlling for multiple climatic factors and ecological attributes of species. We found that relative wing elongation (hand-wing index) and wing area increase with elevation, even when accounting for latitude, temperature seasonality, body mass, habitat, aerial lifestyle, and altitudinal migration. These results confirm a pervasive elevational gradient in avian wing morphology and suggest that aerodynamic constraints linked to air density, perhaps coupled with oxygen deficiency, contribute to global patterns of trait evolution in flying animals.
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