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Journal articleTissot FS, Estrach S, Seguin L, et al., 2025,
Functional transfer of integrin co-receptor CD98hc by small extracellular vesicles improves wound healing in vivo.
, Matrix Biol, Vol: 135, Pages: 99-105Extracellular vesicles (EVs) mediate intercellular communication. EVs are composed of a lipid bilayer and contain cytosolic proteins and RNAs. Studies highlight EVs striking functions in cell-cell crosstalk. Here, we found that small EVs can transfer functional signaling molecules through their lipid bilayer and participate in skin homeostasis. We identified a transmembrane protein CD98hc (a.k.a. SLC3A2), an integrin co-receptor (Itgb1 and Itgb3), implicated in epidermis homeostasis via its capacity in regulating extracellular matrix, as an important mediator of EV-based intercellular communication in vivo. We first demonstrated that healthy dermal fibroblasts produced and secreted EVs bearing characteristic of exosome-like small EVs (sEVs). We show that CD98hc, Itgb1 co-receptor, is present at the surface of sEVs, transferred and stabilized at the plasma membrane. The transferred complex is functional on recipient cells both in vitro and in vivo. Indeed, treatment with sEVs from WT, but not KO cells rescued migratory defects observed either in CD98hc KO dermal fibroblasts or in keratinocytes in vitro. Furthermore, injection of sEVs at the margins of wound in impaired wound healing mouse models (epidermal CD98hc KO mice exhibiting healing defect and elderly mice) improved wound closure in vivo. CD98hc complex transferred from sEVs remained stabilized at least 7 days after injection. Thus, our findings reveal that in vivo treatment with sEVs containing integrin co-receptor CD98hc could improve multiple skin afflictions.
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Journal articleWisden W, Franks N, 2025,
Matters Arising: Reply to: " A curious concept of CNS clearance "
, Nature Neuroscience, ISSN: 1097-6256 -
Journal articleZhong Z, Hocking BJW, Brown CP, et al., 2025,
Synthesis and Functionalization of Sulfoximine‐Bicyclo[1.1.0]butanes: Functionalizable, Tuneable and Cysteine‐Selective Chiral Warheads
, Angewandte Chemie, Vol: 137, ISSN: 0044-8249<jats:title>Abstract</jats:title><jats:p>Electrophilic covalent warheads with appropriate reactivity and selectivity are crucial to the investigation of protein function and the discovery of therapeutics. Here we report the synthesis of sulfoximine bicyclo[1.1.0] butanes (BCBs) as novel thiol reactive chiral warheads, achieved in one‐pot from methylsulfoximines. Unusually the warhead can then be derivatized, keeping the BCB intact, over 3 vectors: i) sulfoximine N‐modification instills a broad range of strain‐release reactivity; ii) sp<jats:sup>2</jats:sup>‐cross‐coupling reactions on aryl‐BCB‐sulfoximines allows direct diversification, and iii) functionalization of the BCB motif itself is achieved by metalation and trapping with electrophiles. The BCB sulfoximines are shown to react selectively with cysteine including in a protein model (CDK2) under biocompatible conditions. Preliminary data indicate suitability for chemoproteomic applications, and enantioselective cysteine‐labelling. The reactivity of sulfoximine BCBs with electron withdrawing groups on nitrogen is comparable to acrylamides with low to moderate reactivity.</jats:p>
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Journal articleAhmad Shaberi HS, Endres RG, Matas-Gil A, et al., 2025,
Optimal network sizes for most robust Turing patterns
, Scientific Reports, ISSN: 2045-2322 -
Journal articleParry C, Turnbull C, Gill R, 2025,
Tracking pollen tube and ovule development in vivo reveals rapid responses to pollination in Brassica napus
, AOB Plants, ISSN: 2041-2851Pollination and subsequent fertilisation in most angiosperms are precursors of seed and fruit development. Thus, understanding the developmental processes can improve management of plant reproductive success and food security. Indeed, the window between ovule fertilisation and seed development is crucial for the accumulation of metabolites which determines ultimate seed quality and yield. Establishing detailed temporal maps of development to describe pollination to early seed development is therefore extremely valuable to provide context for molecular studies, plant breeding, and to refine crop management strategies for optimal seed quality.• MethodsHere, we characterise aspects of post-pollination responses in the globally important crop plant Brassica napus (oilseed rape, canola) with a high-resolution time series of microscope images of the floral organs during the first 48 hours post pollination. • Key results We demonstrate the rapid response to pollination in B. napus (c.v. Westar), with pollen tubes germinating and traversing the style within just four hours. We also describe markers of early seed formation in response to fertilisation in the synchronous development of ovule area and stigma length. • ConclusionsOur results provide a series of temporal benchmarks for post-pollination floral morphology in B. napus, representing valuable reference points for studying and tracking pollination responses and early seed development.
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Journal articleSherry L, Bahar MW, Porta C, et al., 2025,
Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines.
, Nat Commun, Vol: 16Polioviruses have caused crippling disease in humans for centuries, prior to the successful development of vaccines in the mid-1900's, which dramatically reduced disease prevalence. Continued use of these vaccines, however, threatens ultimate disease eradication and achievement of a polio-free world. Virus-like particles (VLPs) that lack a viral genome represent a safer potential vaccine, although they require particle stabilization. Using our previously established genetic techniques to stabilize the structural capsid proteins, we demonstrate production of poliovirus VLPs of all three serotypes, from four different recombinant expression systems. We compare the antigenicity, thermostability and immunogenicity of these stabilized VLPs against the current inactivated polio vaccine, demonstrating equivalent or superior immunogenicity in female Wistar rats. Structural analyses of these recombinant VLPs provide a rational understanding of the stabilizing mutations and the role of potential excipients. Collectively, we have established these poliovirus stabilized VLPs as viable next-generation vaccine candidates for the future.
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Journal articleAhmad N, Nixon PJ, 2025,
Chloroplast alchemy: rewriting the chloroplast genome with high precision
, Trends in Plant Science, ISSN: 1360-1385 -
Journal articleCheaib A, Waring EF, McNellis R, et al., 2025,
Soil nitrogen supply exerts largest influence on leaf nitrogen in environments with the greatest leaf nitrogen demand
, Ecology Letters, ISSN: 1461-023X -
Journal articleBrożek A, Ceccarelli A, Jørgensen ACS, et al., 2025,
Inference of a three-gene network underpinning epidermal stem cell development in Caenorhabditis elegans
, iScience, ISSN: 2589-0042 -
Journal articleYan Y, Antolin N, Zhou L, et al., 2025,
Macrophages excite muscle spindles with glutamate to bolster locomotion
, Nature, Vol: 637, Pages: 698-707, ISSN: 0028-0836The stretch reflex is a fundamental component of the motor system that orchestrates the coordinated muscle contractions underlying movement. At the heart of this process lie the muscle spindles (MS), specialized receptors finely attuned to fluctuations in tension within intrafusal muscle fibres. The tension variation in the MS triggers a series of neuronal events including an initial depolarization of sensory type Ia afferents that subsequently causes the activation of motoneurons within the spinal cord1,2. This neuronal cascade culminates in the execution of muscle contraction, underscoring a presumed closed-loop mechanism between the musculoskeletal and nervous systems. By contrast, here we report the discovery of a new population of macrophages with exclusive molecular and functional signatures within the MS that express the machinery for synthesizing and releasing glutamate. Using mouse intersectional genetics with optogenetics and electrophysiology, we show that activation of MS macrophages (MSMP) drives proprioceptive sensory neuron firing on a millisecond timescale. MSMP activate spinal circuits, motor neurons and muscles by means of a glutamate-dependent mechanism that excites the MS. Furthermore, MSMP respond to neural and muscle activation by increasing the expression of glutaminase, enabling them to convert the uptaken glutamine released by myocytes during muscle contraction into glutamate. Selective silencing or depletion of MSMP in hindlimb muscles disrupted the modulation of the stretch reflex for force generation and sensory feedback correction, impairing locomotor strategies in mice. Our results have identified a new cellular component, the MSMP, that directly regulates neural activity and muscle contraction. The glutamate-mediated signalling of MSMP and their dynamic response to sensory cues introduce a new dimension to our understanding of sensation and motor action, potentially offering innovative therapeutic approaches in conditions that affect s
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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, ISSN: 1574-9541 -
Journal articleSeddon C, David S, Wong J, et al., 2025,
Cryo-EM structure and evolutionary history of the conjugation surface exclusion protein TraT
, Nature Communications, ISSN: 2041-1723Conjugation plays a major role in dissemination of antimicrobial resistance genes. Following transfer of IncF-like plasmids, recipients become refractory to a second wave of conjugation with the same plasmid via entry (TraS) and surface (TraT) exclusion mechanisms. Here, we show that TraT from the pKpQIL and F plasmids (TraTpKpQIL and TraTF) exhibits plasmid surface exclusion specificity. The cryo-EM structures of TraTpKpQIL and TraTF reveal that they oligomerise into decameric champagne bottle cork-like structures, which are anchored to the outer membrane via a diacylglycerol and palmitic acid modified α-helical barrel domain. Unexpectedly, we identify chromosomal TraT homologues from multiple Gram-negative phyla which form numerous divergent lineages in a phylogenetic tree of TraT sequences. Plasmid-associated TraT sequences are found in multiple distinct lineages, including two separate clades incorporating TraT from Enterobacteriaceae IncF/F-like and Legionellaceae F-like plasmids. These findings suggest that different plasmid backbones have acquired and co-opted TraT on independent occasions.6
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Journal articleRukavina K, Staunton J, Zinzalias P, et al., 2025,
Wearable devices may aid the recognition of fluctuation-related pain in Parkinson’s disease—An exploratory, cross-sectional analysis of two prospective observational studies
, PLOS ONE, Vol: 20, Pages: e0316563-e0316563<jats:p>Fluctuation-related pain (FRP) affects more than one third of people with Parkinson’s disease (PwP, PD) and has a harmful effect on health-related quality of life (HRQoL), but often remains under-reported by patients and neglected by clinicians. The National Institute for Health and Care Excellence (NICE) recommends The Parkinson KinetiGraph<jats:sup>TM</jats:sup> (the PKG<jats:sup>TM</jats:sup>) for remote monitoring of motor symptoms. We investigated potential links between the PKG<jats:sup>TM</jats:sup>-obtained parameters and clinical rating scores for FRP in PwP in an exploratory, cross-sectional analysis of two prospective studies: “<jats:italic>The Non-motor International Longitudinal</jats:italic>, <jats:italic>Real-Life Study in PD—NILS</jats:italic>” and “<jats:italic>An observational-based registry of baseline PKG™ in PD—PKGReg</jats:italic>”. 63 PwP (41.3% female; age: 64.24±9.88 years; disease duration, DD: 6.83±5.63 years; Hoehn and Yahr Stage, H&Y: 2 (1–4); Levodopa Equivalent Daily Dose 535 (0–3230) mg) were included. PwP with FRP (n = 23) had longer DD (8.88 (1.29–19.05) vs. 3.16 (0.34–28.92), <jats:italic>p</jats:italic> = 0.001), higher severity of motor symptoms (H&Y 3 (1–4) vs. 2 (1–4), <jats:italic>p</jats:italic> = 0.015; SCOPA Motor total score 21.35±10.19 vs. 13.65±8.99, <jats:italic>p</jats:italic> = 0.003), more dyskinesia (SCOPA Motor Item 18 ≥1 60.9% vs. 7.5%, <jats:italic>p</jats:italic><0.001), and worse HRQoL (PDQ-8 Total Score 10.74±5.98 vs. 6.78±5.13, <jats:italic>p</jats:italic> = 0.007) then PwP without FRP (n = 40). In the multivariate logistic regression, after the adjustment for DD, H&Y and SCOPA-Motor total score, the presence
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Journal articleMarsh CJ, Turner EC, Blonder BW, et al., 2025,
Tropical forest clearance impacts biodiversity and function, whereas logging changes structure.
, Science, Vol: 387, Pages: 171-175The impacts of degradation and deforestation on tropical forests are poorly understood, particularly at landscape scales. We present an extensive ecosystem analysis of the impacts of logging and conversion of tropical forest to oil palm from a large-scale study in Borneo, synthesizing responses from 82 variables categorized into four ecological levels spanning a broad suite of ecosystem properties: (i) structure and environment, (ii) species traits, (iii) biodiversity, and (iv) ecosystem functions. Responses were highly heterogeneous and often complex and nonlinear. Variables that were directly impacted by the physical process of timber extraction, such as soil structure, were sensitive to even moderate amounts of logging, whereas measures of biodiversity and ecosystem functioning were generally resilient to logging but more affected by conversion to oil palm plantation.
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Journal articleCai W, Zhu Z, Harrison SP, et al., 2025,
A unifying principle for global greenness patterns and trends
, Nature Communications Earth and Environment, ISSN: 2662-4435 -
Journal articlePurvis A, 2025,
Bending the curve of biodiversity loss requires a 'satnav' for nature.
, Philos Trans R Soc Lond B Biol Sci, Vol: 380Georgina Mace proposed bending the curve of biodiversity loss as a fitting ambition for the Convention on Biological Diversity. The new Global Biodiversity Monitoring Framework (GBMF) may increase the chances of meeting the goals and targets in the Kunming-Montreal Global Biodiversity Framework (KMGBF), which requires bending the curve. To meet the outcome goals of KMGBF, the GBMF should support adaptive policy responses to the state of biodiversity, which in turn requires a 'satnav' for nature. The twin pillars of such a satnav are (i) models to predict expected future outcomes of today's choices; and (ii) rapid feedback from monitoring to enable course corrections and model improvement. These same elements will also empower organizations to ensure that their actions are truly nature-positive, but they are not yet written into the GBMF. Without a satnav, society will effectively have to try to find its way to the outcome goals by looking in the rear-view mirror that the current headline indicators provide. Drawing contrasts and parallels with climate modelling, I discuss challenges for indicators, models, data and research culture that must be overcome if we are to bend the curve, and suggest ways forward.This article is part of the discussion meeting issue 'Bending the curve towards nature recovery: building on Georgina Mace's legacy for a biodiverse future'.
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Journal articleBridle J, Balmford A, Durant SM, et al., 2025,
Dedication: Professor Dame Georgina Mace DBE FRS (1953-2020).
, Philos Trans R Soc Lond B Biol Sci, Vol: 380 -
Journal articleBezeng BS, Ameka G, Angui CMV, et al., 2025,
An African perspective to biodiversity conservation in the 21st century
, Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 380, ISSN: 0962-8436Africa boasts high biodiversity while also being home to some of the largest and fastest-growing human populations. Although the current environmental footprint of Africa is low compared to other continents, the population of Africa is estimated at around 1.5 billion inhabitants, representing nearly 18% of the world's total population. Consequently, Africa’s rich biodiversity is under threat, yet only 19% of the landscape and 17% of the seascape are under any form of protection. To effectively address this issue and align with the Convention on Biological Diversity's ambitious ‘30 by 30’ goal, which seeks to protect 30% of the world's land and oceans by 2030, substantial funding and conservation measures are urgently required. In response to this critical challenge, as scientists and conservationists working in Africa, we propose five recommendations for future directions aimed at enhancing biodiversity conservation for the betterment of African society: (i) accelerate data collection, data sharing and analytics for informed policy and decision making; (ii) innovate education and capacity building for future generations; (iii) enhance and expand protected areas, ecological networks, and foundational legal frameworks; (iv) unlock creative funding channels for cutting-edge conservation initiatives; and (v) integrate indigenous and local knowledge into forward-thinking conservation strategies. By implementing these recommendations, we believe Africa can make significant strides towards preserving its unique biodiversity, while fostering a healthier society, and contributing to global conservation efforts.
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Journal articleBridle J, Balmford A, Durant SM, et al., 2025,
How should we bend the curve of biodiversity loss to build a just and sustainable future?
, Philos Trans R Soc Lond B Biol Sci, Vol: 380Current rates of habitat and biodiversity loss, and the threat they pose to ecological and economic productivity, would be considered a global emergency even if they were not occurring during a period of rapid anthropogenic climate change. Diversity at all levels of biological organization, both within and among species, and across genomes and communities, is critical for the resilience of the world's ecosystems in the face of such change. However, it remains an urgent scientific challenge to understand how biodiversity underpins these ecological outputs, how patterns of biodiversity are being affected by current threats, and how and where such biodiversity contributes most directly to human economies, well-being and social justice. In addition, even with such scientific understanding, there is a pressing need for societies to incorporate biodiversity protection into their economies and governance, and to stop subsidizing the loss of humanity's future prosperity for short-term private benefit. We highlight key issues and ways forward in these areas, inspired by the research and career of Dame Georgina Mace FRS, and by our discussions during the Royal Society meeting of June 2023.This article is part of the discussion meeting issue 'Bending the curve towards nature recovery: building on Georgina Mace's legacy for a biodiverse future'.
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Journal articleLuo S, Li X-R, Gong X-T, et al., 2025,
Trojan horse peptide conjugates remodel the activity spectrum of clinical antibiotics.
, Proc Natl Acad Sci U S A, Vol: 122Infections caused by gram-negative pathogens continue to be a major risk to human health because of the innate antibiotic resistance endowed by their unique cell membrane architecture. Nature has developed an elegant solution to target gram-negative strains, namely by conjugating toxic antibiotic warheads to a suitable carrier to facilitate the active import of the drug to a specific target organism. Microcin C7 (McC) is a Trojan horse peptide-conjugated antibiotic that specifically targets enterobacteria by exploiting active import through oligopeptide transport systems. Here, we characterize the molecular mechanism of McC recognition by YejA, the solute binding protein of the Escherichia coli oligopeptide transporter. Structure-guided mutational and functional analysis elucidates the determinants of substrate recognition. We demonstrate that the peptide carrier can serve as a passport for the entry of molecules that are otherwise not taken into E. coli cells. We show that peptide conjugation can remodel the antibiotic spectrum of clinically relevant parent compounds. Bioinformatics analysis reveals a broad distribution of YejA-like transporters in only the Proteobacteria, underscoring the potential for the development of Trojan horse antibiotics that are actively imported into such gram-negative bacteria.
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Journal articleTolosana I, Willis K, Gribble M, et al., 2025,
A Y chromosome-linked genome editor for efficient population suppression in the malaria vector Anopheles gambiae.
, Nat Commun, Vol: 16Genetic control - the deliberate introduction of genetic traits to control a pest or vector population - offers a powerful tool to augment conventional mosquito control tools that have been successful in reducing malaria burden but that are compromised by a range of operational challenges. Self-sustaining genetic control strategies have shown great potential in laboratory settings, but hesitancy due to their invasive and persistent nature may delay their implementation. Here, instead, we describe a self-limiting strategy, designed to have geographically and temporally restricted effect, based on a Y chromosome-linked genome editor (YLE). The YLE comprises a CRISPR-Cas9 construct that is always inherited by males yet generates an autosomal dominant mutation that is transmitted to over 90% of the offspring and results in female-specific sterility. To our knowledge, our system represents a pioneering approach in the engineering of the Y chromosome to generate a genetic control strain for mosquitoes. Mathematical modelling shows that this YLE technology is up to seven times more efficient for population suppression than optimal versions of other self-limiting strategies, such as the widely used Sterile Insect Technique or the Release of Insects carrying a Dominant Lethal gene.
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Book chapterBolan N, Srinivasarao C, Rocco C, et al., 2025,
Zinc in soil-crop-animal-human health continuum
, Advances in Agronomy, Pages: 1-61Globally, zinc (Zn) deficiency in soils, and subsequently crops, has emerged as one of the most prevalent among micronutrients, resulting in a severe decline in crop yields and nutritional quality and in adversely affecting animal and human health. Worldwide, more than half of the agricultural soils are inherently deficient in Zn, and the health of about one-third of the global human population is impacted by Zn deficiency. Zinc is an essential micronutrient for animal and human health, and, in the developing world, Zn deficiency has been identified as the fifth cause of disease and death for humans. The World Health Organization (WHO) reports that annually more than 800,000 people, including around 450,000 children under the age of 5, die due to Zn deficiency. Zinc supplementation was frequently associated with boosting immunity against COVID-19 in recent years. Because most of the Zn in animals and humans is derived from soil-grown crops, their source of Zn is highly dependent on plant Zn, especially in crops or fodder; in turn, crop Zn is dependent on available soil Zn levels. This integrated review describes Zn distribution, behavior, and fate in soils and its uptake and role in plants and crop production, as well as in the well-being of animals and humans. It discusses recent findings concerning Zn deficiency in all steps of the human food chain (from soil, to crop, animal, and human), and how it can be addressed through novel Zn fertilizers, soil amendments, and biofortification of Zn.
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Journal articleLi H, Tang X, Yang T, et al., 2025,
Reinvestigation into the role of lipopolysaccharide Glycosyltransferases in pylori protein glycosylation
, Gut Microbes, Vol: 17, ISSN: 1949-0976Protein glycosylation has been considered as a fundamental phenomenon shared by all domains of life. In Helicobacter pylori, glycosylation of flagellins A and B with pseudaminic acid have been rigorously confirmed and shown to be essential for flagella assembly and bacterial colonization. In addition to flagellins, several other proteins including RecA, AlpA/B, and BabA/B in H. pylori have also been reported to be glycosylated and to be dependent on the lipopolysaccharide (LPS) biosynthetic pathway. However, these proteins have not been purified for sugar-specific staining or structural analysis to confirm the existence of carbohydrate motifs. Here, using a combined approach of genetics, protein purification, and sugar-specific staining, we demonstrate that RecA is not a glycoprotein. Moreover, using LPS-protein reconstitution experiments, we demonstrate that the presence of O-antigen containing full-length LPS interferes with the electrophoretic mobility of H. pylori RecA and many other proteins including AlpA/B on SDS-PAGE. Finally, we demonstrate that full-length LPS extracted from E. coli affects electrophoretic migration of H. pylori proteins, while full-length LPS extracted from H. pylori similarly influences the electrophoretic migration of E. coli proteins. The impact is more subtle with E. coli LPS compared to H. pylori LPS, indicating that the magnitude of effect of LPS effects on protein mobility is dependent on bacterial source of the LPS. These findings suggest that the effects of full-length LPS on protein electrophoresis may represent a more general phenomenon. As LPS is a unique component of virtually all Gram-negative bacteria, our data suggest that when observing protein electrophoretic mobility shifts between wild-type and LPS mutant strains or between subcellular fractionation samples, the influence of LPS on protein electrophoretic migration should be considered first, rather than interpreting it as potential protein glycosylation that is depend
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Journal articleZhong Z, Hocking B, Brown C, et al., 2025,
Synthesis and functionalization of sulfoximine-bicyclo[1.1.0]butanes: functionalizable, tuneable and cysteine-selective chiral warheads
, Angewandte Chemie International Edition, Vol: 64, ISSN: 1433-7851Electrophilic covalent warheads with appropriate reactivity and selectivity are crucial to the investigation of protein function and the discovery of therapeutics. Here we report the synthesis of sulfoximine bicyclo[1.1.0]butanes (BCBs) as novel thiol reactive chiral warheads, achieved in one-pot from methylsulfoximines. Unusually the warhead can then be derivatized, keeping the BCB intact, over 3 vectors: i) sulfoximine N-modification instills a broad range of strain-release reactivity; ii) sp2-cross-coupling reactions on aryl-BCB-sulfoximines allows direct diversification, and iii) functionalization of the BCB motif itself is achieved by metalation and trapping with electrophiles. The BCB sulfoximines are shown to react selectively with cysteine including in a protein model (CDK2) under biocompatible conditions. Preliminary data indicate suitability for chemoproteomic applications, and enantioselective cysteine-labelling. The reactivity of sulfoximine BCBs with electron withdrawing groups on nitrogen is comparable to acrylamides with low to moderate reactivity.
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Journal articlePowell HR, Islam SA, David A, et al., 2025,
Phyre2.2: A Community Resource for Template-based Protein Structure Prediction
, Journal of Molecular Biology, ISSN: 0022-2836Template-based modelling, also known as homology modelling, is a powerful approach to predict the structure of a protein from its amino acid sequence. The approach requires one to identify a sequence similarity between the query sequence and that of a known structure as they will adopt a similar conformation, and the known structure can be used as the template for modelling the query sequence. Recently several approaches, most notably AlphaFold, have employed enhanced machine learning and have yielded accurate models irrespective of whether there is an identifiable template. Here we report Phyre2.2 which incorporates several enhancements to our widely-used template modelling portal Phyre2. The main development is facilitating a user to submit their sequence and then Phyre2.2 identifies the most suitable AlphaFold model to be used as a template. In Phyre2.2 the user searches a template library of known structures. We have now included in our library a representative structure for every protein sequence in the protein databank (PDB). In addition, there are representatives for an apo and a holo structure if they are in the PDB. The ranking of hits has been modified to highlight to the user if there are different domains spanning the sequence. Phyre2.2 continues to support batch processing where a user can submit up to 100 sequences facilitating processing of proteomes. Phyre2.2 is freely available to all users, including commercial users, at https://www.sbg.bio.ic.ac.uk/phyre2/.
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Journal articlePickering G, O'Keeffe M, Bannister K, et al., 2025,
A pain research strategy for Europe: A European survey and position paper of the European Pain Federation <scp>EFIC</scp>
, European Journal of Pain, Vol: 29, ISSN: 1090-3801<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Pain is the leading cause of disability and reduced quality of life worldwide. Despite the increasing burden for patients and healthcare systems, pain research remains underfunded and under focused. Having stakeholders identify and prioritize areas that need urgent attention in the field will help focus funding topics, reduce ‘research waste’, improve the effectiveness of pain research and therapy and promote the uptake of research evidence. In this study, the European Pain Federation (EFIC) developed a Pain Research Strategy for Europe.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The study used multiple methods, including literature searches, multidisciplinary expert debate, a survey and a final consensus meeting. The cross‐sectional survey was conducted among 628 European pain researchers, clinicians, educators and industry professionals to obtain the rating and hierarchy of pain research priorities.</jats:p><jats:p>The final consensus meeting involved a multidisciplinary expert panel including people with lived experience from 23 countries. The survey results guided discussions where top priorities were agreed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Content analysis identified nine survey themes, of which five emerged as top priorities: (i) understand the pathophysiology of pain; (ii) understand and address comorbidities; (iii) critically assess current therapies; (iv) develop new treatments; and (v) explore the biopsychosocial impacts of pain. Physical, psychological and social approaches were prioritized at the same level as pharmacological treatments. The top priorities were endorsed by a multidisciplinary expert panel. The panel emphasized the importance of also clearly communicating the con
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Journal articleLyons-White J, Zodua PA, Yobo CM, et al., 2025,
Challenges for implementing zero deforestation commitments in a highly forested country: Perspectives from Liberia's palm oil sector
, WORLD DEVELOPMENT, Vol: 185, ISSN: 0305-750X -
Journal articleReen V, D'Ambrosio M, Søgaard PP, et al., 2025,
SMARCA4 regulates the NK-mediated killing of senescent cells
, Science Advances, Vol: 11, ISSN: 2375-2548Induction of senescence by chemotherapeutic agents arrests cancer cells and activates immune surveillance responses to contribute to therapy outcomes. In this investigation, we searched for ways to enhance the NK-mediated elimination of senescent cells. We used a staggered screen approach, first identifying siRNAs potentiating the secretion of immunomodulatory cytokines to later test for their ability to enhance NK-mediated killing of senescent cells. We identified that genetic or pharmacological inhibition of SMARCA4 enhanced senescent cell elimination by NK cells. SMARCA4 expression is elevated during senescence and its inhibition derepresses repetitive elements, inducing the SASP via activation of cGAS/STING and MAVS/MDA5 pathways. Moreover, a PROTAC targeting SMARCA4 synergized with cisplatin to increase the infiltration of CD8 T cells and mature, activated NK cells in an immunocompetent model of ovarian cancer. Our results indicate that SMARCA4 inhibitors enhance NK-mediated surveillance of senescent cells and may represent senotherapeutic interventions for ovarian cancer.
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Journal articleStocker B, Dong N, Perkowski EA, et al., 2025,
Empirical evidence and theoretical understanding ofecosystem carbon and nitrogen cycle interactions
, New Phytologist, Vol: 245, Pages: 49-68, ISSN: 0028-646XInteractions between carbon (C) and nitrogen (N) cycles in terrestrial ecosystems are simulated in advanced vegetation models, yet methodologies vary widely, leading to divergent simulations of past land C balance trends. This underscores the need to reassess our understanding of ecosystem processes, given recent theoretical advancements and empirical data. We review current knowledge, emphasising evidence from experiments and trait data compilations for vegetation responses to CO2 and N input, alongside theoretical and ecological principles for modelling. N fertilisation increases leaf N content but inconsistently enhances leaf-level photosynthetic capacity. Whole-plant responses include increased leaf area and biomass, with reduced root allocation and increased aboveground biomass. Elevated atmospheric CO2 also boosts leaf area and biomass but intensifies belowground allocation, depleting soil N and likely reducing N losses. Global leaf traits data confirm these findings, indicating that soil N availability influences leaf N content more than photosynthetic capacity. A demonstration model based on the functional balance hypothesis accurately predicts responses to N and CO2 fertilisation on tissue allocation, growth and biomass, offering a path to reduce uncertainty in global C cycle projections.
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Book chapterDey S, Majumdar A, Dubey PK, et al., 2025,
Involvement of soil parameters and rhizosphere microbiome in sustainable crop productivity
, Rhizomicrobiome in Sustainable Agriculture and Environment, Publisher: Elsevier, Pages: 189-228, ISBN: 9780443236914
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