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  • Journal article
    Hui T-Y, Epopa PS, Millogo AA, Yao FA, Koulmaga D, Noulin F, Diabate A, Burt Aet al., 2026,

    Variance partitioning reveals contrasting random effect contributions to the density and species composition of malaria-transmitting mosquitoes in Western Burkina Faso

    , Parasites and Vectors, Vol: 19, ISSN: 1756-3305

    Background Spatial-temporal variation exists in the density and species composition of malaria-carrying mosquitoes, which will in turn influence the transmission of the disease. While there has been extensive research on seasonality and other main drivers of the vector populations, the heterogeneity partitioned as random effects at various spatial-temporal scales is just as important but has not attracted the same attention. Methods To investigate the relative contributions of the between-house, between-village, and between year variations, as well as other house-level covariates such as inhabitant number and bed net usage on vector density and species composition, intensive Pyrethroid Spray Catches (PSC) sampling was conducted across a 60-month period between 2012-2019 from four villages in the Sudano-Sahelian region of Burkina Faso. Results For density, measured by female Anopheles gambiae s.l. counts, our modelling showed that the between-house variation was the largest variance component, followed by the between year then between-village variation, after accounting for seasonality and other covariates. Density increased with the number of inhabitants within a household but was uncorrelated with bed net presence. A subset of female mosquitoes was genotyped for species identification, and the composition of An. coluzzii and An. gambiae, the two dominant vectors in the region, varied markedly across villages without an overall trend. The between-village variance contributed up to 76% of the total random variation in species composition, followed by the between-year variance. The between-house variation was statistically insignificant. Neither household size nor bed net usage had any impact on species composition. Conclusions Interestingly, the between-house component of variation was the largest contributor when measuring mosquito density, but it was the least important for species composition. For between-village variation the converse was found. Together with
  • Journal article
    Maia RA, Oki Y, Medina I, Figueiredo JCG, Barbosa M, Pereira EG, Aguirre-Gutiérrez J, Fernandes GWet al., 2026,

    Atlantic forest tree enhances photoprotective and thermotolerance in soils contaminated by mining tailings

    , Theoretical and Experimental Plant Physiology, Vol: 38

    Large-scale mining disasters in tropical regions impose long-term pressures on ecosystems by degrading soil fertility and exposing native vegetation to chemical and physical disturbances. This study investigates whether Eugenia florida, a native tree species found in both tailings-impacted and reference areas of the Rio Doce Basin in Brazil, exhibits physiological adjustments that confer resilience to combined edaphic and thermal constraints. We assessed soil properties and 16 physiological traits related to nutrient status, photosynthetic efficiency, photoprotection, and thermal tolerance. Soils in the impacted area exhibited markedly lower organic matter, cation exchange capacity, and nutrient concentrations, along with increased iron concentration. Despite a 10% reduction in nitrogen balance index, plants in the impacted area exhibited 10% more chlorophyll and 19% more flavonoids, indicating compensatory pigment production and enhanced antioxidant capacity. Photosynthetic performance remained stable across environments, but individuals in the impacted area displayed elevated regulated energy dissipation and reduced unregulated energy loss, suggesting efficient photoprotective adjustments. Transient fluorescence analyses revealed intensified excitation fluxes and greater heat dissipation per reaction centre. Thermal thresholds, defined as temperatures causing 15% and 50% reductions in photosynthetic efficiency, were significantly higher in impacted individuals. Multivariate analyses identified excitation flux traits as key predictors of thermal resilience. Physiological function in E. florida is sustained through integrated plastic responses under long-term soil degradation and thermal constraints. Its ability to modulate energy fluxes and antioxidant defences highlights its potential as a candidate species for ecological restoration in tropical regions increasingly affected by human disturbance and climate extremes.
  • Journal article
    Wan Y, Wong JLC, Sanchez-Garrido J, Low WW, Turton JF, Morecchiato F, Baccani I, Dodgson K, Rossolini GM, Woodford N, Frankel G, Jauneikaite E, Meunier D, Hopkins KLet al., 2026,

    Genomic and molecular characterisation of a KPC-producing Klebsiella pneumoniae clinical isolate resistant to meropenem-vaborbactam, imipenem-relebactam, and ceftazidime-avibactam

    , BMC Genomic Data, Vol: 27, ISSN: 2730-6844

    Background Resistance to carbapenems and third-generation cephalosporins is increasing in Klebsiella pneumoniae globally, restricting therapeutic options. The β-lactam/β-lactamase inhibitor combinations are widely used to circumvent β-lactamase-mediated resistance. In 2021, an unusual K. pneumoniae clinical isolate, KpMVR1, was recovered from a hospitalised patient in England, exhibiting resistance to meropenem-vaborbactam, imipenem-relebactam, and ceftazidime-avibactam. To investigate this phenomenon, we characterised the genome and antimicrobial susceptibility of KpMVR1 alongside two clonally related isolates susceptible to all three β-lactam/β-lactamase inhibitor combinations: KpMVS1, collected from the same patient 42 days earlier, and KpMVS2, from another patient in the same hospital. Methods Illumina and MinION whole-genome sequencing were conducted for these three isolates, followed by hybrid genome assembly. Annotated genome assemblies were compared to identify genetic variation. Mutagenesis experiments were performed to verify predicted functional alterations. Results All isolates belonged to clone ST8134 and carried blaKPC-2 alleles (KpMVR1: blaKPC-157; KpMVS1 and KpMVS2: blaKPC-2) in plasmids predicted to be conjugative. Insertion sequence ISEc68 caused a frameshift mutation in KpMVR1’s ompK36 gene, reducing susceptibility to meropenem-vaborbactam and imipenem-relebactam. KPC-157 demonstrated decreased hydrolysis of imipenem and ceftazidime when compared with KPC-2. KpMVR1 also encoded a disrupted transcriptional repressor MarR and a destabilising mutation in AcrB, a component of the AcrAB-TolC multidrug efflux pump. An intact, iron-transporting fec operon was identified on a novel IncFII(pKP91)/IncFIB(K) plasmid unique to KpMVS2, possibly accounting for the cefiderocol resistance observed in this isolate. ConclusionsKpMVR1 carried multiple resistance-associated genetic alterations and likely developed its resistance profile
  • Journal article
    De Lorm TA, Heon SP, Bernard H, Ewers RMet al., 2026,

    Bird and mammal communities transform without collapsing in response to oil palm replanting

    , Forest Ecology and Management, Vol: 619, ISSN: 0378-1127

    Replanting a tree plantation - that is, clearing old trees and replacing these with young plants - drastically alters its habitat structure and microclimate, leading to changes in its biodiversity. Nevertheless, we lack an understanding of how the replanting of oil palm plantations - the most prominent oil crop globally - affects mammals and birds, while the amount of area replanted will increase exponentially over the next decades. We therefore studied how the bird and mammal community of an oil palm plantation in Malaysian Borneo changed in response to replanting. Using camera traps for mammals, and acoustic recordings and BirdNET for birds, we show that both communities are transformed. Mammal species richness slightly dropped, because of the absence from replanted plantations of long- and pig-tailed macaques (Macaca fascicularis and M. nemestrina), both endangered primate species. Bird species richness did not significantly differ between replanted and mature plantations. However, the detection frequency of most species changed, as the bird community shifted from forest and woodland species towards open-habitat species. The detection frequency and species richness of different trophic niches stayed largely constant, indicating that birds will still be able to perform similar high-level ecological functions in replanted plantations. Overall, our results show that replanting reshaped mammal and bird communities, but that their diversity and abundance does not collapse. These findings stress the importance of staggered replanting, as opposed to replanting large stretches of plantation in one go, to bolster landscape level biodiversity, and underscore that tree plantations are temporally dynamic habitats.
  • Journal article
    Casadio R, Lu ZJ, Mathews DH, Sternberg MJEet al., 2026,

    Computational Resources for Molecular Biology 2026.

    , J Mol Biol, Vol: 438
  • Journal article
    Conev A, Islam SA, Tsitsa I, David A, Sternberg MJEet al., 2026,

    3DSeqCheck: a web-based tool for verifying sequence consistency between a 3D structure file and the corresponding UniProt entry

    , Journal of Molecular Biology, Vol: 438, ISSN: 0022-2836

    UniProt is a central repository of protein sequences and annotations, with entries being updated several times a year as new sequencing evidence is collected. By contrast, protein structure resources often evolve at a different pace. The AlphaFold database remained unchanged for four years, until September 2025, during which time nearly 3% of the associated sequences underwent revisions in UniProt. In a range of bioinformatics tasks, protein structure data is paired with sequence annotations from UniProt. Mapping annotations to outdated structure files can lead to errors in downstream analysis. While this concern has been addressed for experimental structures, efforts for the modeled structures are lacking. 3DSeqCheck is a lightweight web tool that enables quick comparison of the sequence of modeled and experimental structures to the latest UniProt entries. 3DSeqCheck provides an interactive visual panel of the alignment and the comparison of the residue numbering and can be accessed freely at: https://missense3d.bc.ic.ac.uk/3dseqcheck and https://github.ic.ac.uk/ImperialCollegeLondon/check3Dseq.
  • Journal article
    Zhao H, Pye R, Walker G, Tran W, Simmonds O, Tsitsa I, Islam S, Hanna G, David Aet al., 2026,

    Missense3D-PTMdb: a web tool for visualising and exploring human genetic variants and post-translational modification sites using alphafold models

    , Journal of Molecular Biology, Vol: 438, ISSN: 0022-2836

    Only a fraction of the >11 million missense variants identified in humans has a known clinical significance. Post-translational modifications (PTMs), such as phosphorylation, glycosylation and ubiquitination, are key regulators of protein function and structure. PTMs depend on correct protein folding and the recognition and binding of enzymes to specific amino acid motifs near modification sites. AlphaFold models provide an unprecedented opportunity to explore variants on 3D structures, enabling systematic identification of amino acid substitutions that could affect PTMs and should be further investigated experimentally.We present Missense3D-PTMdb, a “one-stop-shop” interactive web tool that provides a user-friendly sequence-structure mapping of 20,235 human proteins, 11,5 million naturally occurring human missense variants, >60 PTM types and 203,775 PTM residues and their neighbours in sequence and 3D structure space using AlphaFold models of the human proteome. The resource also supports visualisation of novel variants not in the database. Missense3D-PTMdb is freely available at https://missense3d.bc.ic.ac.uk/ptmdb.
  • Journal article
    Di Domenico F, Kucharczyk MW, Patel R, Bannister Ket al., 2026,

    Perioperative pregabalin does not alter behavioural or diffuse noxious inhibitory control responses in 2 rat models of chronic pain

    , PAIN Reports, Vol: 11

    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Introduction:</jats:title> <jats:p>Multiple mechanisms contribute to the experience of pain where the use of model organisms to dissect mechanistically sensory regulatory circuitry is a vital component of discovering underlying causes of persistent pain in disease states. Such disease states can be modelled in animals using surgical procedures that, ethically, should involve administration of analgesia. However, since basic pain researchers often wish to measure pain-related events, animals may be denied perioperative analgesia to avoid adversely influencing experimental outcomes.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>We conducted a structured review of perioperative analgesia usage in rat spinal nerve ligation (SNL) and cancer-induced bone pain (CIBP) models. Using a combination of behavioural testing and in vivo electrophysiology in the dorsal horn of the spinal cord, we assessed the impact of perioperative pregabalin on nociceptive behaviours in the acute recovery phase, and behavioural and electrophysiological experimental outcomes in the established phase, of rat SNL and CIBP models.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>A literature search revealed that, for studies using rat models of SNL or CIBP, only 5.37% and 12.69%, respectively, reported the use of perioperative analgesia. We then demonstrated that the use of pregabalin as a perioperative analgesic reduced mechanical hypersensitivity in the acute period after SNL surgery, with no impact on behavioural, electrophysiological, or neuropharmacological outcomes in the established p
  • Journal article
    Ferrando-Marco M, Berger S, Barkoulas M, 2026,

    Transcriptional feedback targeting Wnt pathway components reveals hidden heterogeneity in Caenorhabditis elegans seam cell lineages.

    , Genetics, Vol: 233

    Asymmetric cell division in the epidermal stem cells of Caenorhabditis elegans, known as seam cells, relies on the Wnt/β-catenin asymmetry pathway to generate daughter cells with distinct fates. However, whether components of this pathway are transcriptionally regulated during these divisions remains unclear. Here, we employ single-molecule fluorescence in situ hybridization to quantify mRNA distributions of key Wnt pathway components during L2 symmetric and asymmetric seam cell divisions. We find that transcripts encoding the negative regulators pry-1/Axin and apr-1/APC are enriched in posterior daughter cells, while those encoding the positive regulators sys-1/β-catenin, wrm-1/β-catenin, and lit-1/NLK, along with the transcription factor pop-1/TCF, are enriched in anterior daughter cells. Strikingly, molecular asymmetries are already evident following the L2 symmetric division, with anterior and posterior daughters exhibiting distinct levels of Wnt component expression and Wnt pathway activation. These mRNA distributions are surprising considering the established protein localizations that underpin the Wnt asymmetry model and suggest extensive postdivisional transcriptional regulation. We further demonstrate that pop-1 and pry-1 asymmetric expression partly depends on Wnt signaling activity. Investigation of protein distributions using knock-in reporters for PRY-1 and CAM-1 showed that protein accumulation patterns at L2 are consistent with transcript levels. Our findings uncover transcriptional feedback within the Wnt pathway that may reinforce robust fate specification and reveal molecular heterogeneity in seam cells with potential functional consequences for lineage behavior.
  • Journal article
    Ferrando-Marco M, Lin S, Del Valle BG, Hintze M, Narunsky L, Huang J, Edwards S, Barkoulas Met al., 2026,

    HDAC1/2-mediated repression of Wnt receptor expression orients asymmetric division polarity in C. elegans.

    , Development

    Asymmetric cell division generates distinct daughter cells essential for tissue development, yet the mechanisms orienting division polarity within tissues remain incompletely understood. Here, we uncover a role for chromatin-mediated transcriptional repression in controlling polarity orientation during asymmetric division of C. elegans epidermal stem cells, known as the seam cells. Tissue-specific loss of the class I histone deacetylase hda-1, homologous to mammalian HDAC1/2, causes polarity reversals and reduces molecular asymmetry between daughter cells. Using Targeted DamID, we identify the Wnt receptors lin-17/Frizzled and cam-1/Ror as key targets. Single-molecule FISH reveals opposing expression gradients along the body axis, with cam-1 enriched anteriorly and lin-17 posteriorly. In hda-1 mutants, both receptors are upregulated and differences between seam cells are flattened. Overexpression of either receptor alone is sufficient to reproduce the polarity reversals, while co-overexpression produces additive effects. The polarity phenotype is independent of the canonical NuRD and SIN3 complexes, suggesting that HDA-1 acts through an alternative mechanism. These findings link histone deacetylase activity to Wnt receptor expression and suggest that graded receptor expression may provide cues that orient asymmetric division polarity.
  • Journal article
    Oh J, Jiménez JI, Kim J, 2026,

    Safe and resource-aware microbial design for food production

    , Current Opinion in Biotechnology, Vol: 100, ISSN: 0958-1669

    Precision fermentation is redefining microbial food manufacturing by enabling programmable biosynthesis of nutrients and functional ingredients. Despite this progress, industrial-scale deployment is limited by metabolic burden, growth-production trade-offs, biosafety concerns, and the costs of downstream processing. Conventional intracellular systems inherently generate host-derived impurities and endotoxins, challenging food-grade standards. Here, we review platform-level advances that decouple biosynthesis from cellular constraints and streamline process design, with a focus on approaches aligned to food industry requirements. We highlight cell-free systems and non-replicative minicells as intrinsically contained production chassis, detail advances in secretion and efflux engineering for efficient extracellular product recovery, and discuss division-of-labor microbial consortia to address resource allocation limits. Together, these innovations integrate biosafety and process efficiency, providing a safe-by-design framework for next-generation microbial food systems that meet both regulatory and industrial needs.
  • Journal article
    Bose A, Bopanna Y, Shetty P, Sharma K, Mathew JKK, Mishra V, Bannerjee S, Ramani H, Pulimood AB, Bhat R, Shenoy AR, Visweswariah SSet al., 2026,

    Therapeutic zinc targets dysregulated GC-C signaling and restores ileal defects in a preclinical model of familial diarrheal disease.

    , Am J Physiol Gastrointest Liver Physiol, Vol: 331, Pages: G125-G139

    Hyperactivating mutations in guanylyl cyclase C (GC-C) are monogenic causes of early-onset inflammatory bowel disease, familial diarrheal syndrome, and congenital secretory diarrhea. The mechanisms linking elevated cGMP levels to immune imbalance remain poorly defined. Here, using a preclinical model of a disease-associated GC-C mutation, we observe pleiotropic alterations in the small intestinal epithelium. Transcriptomic and functional analyses revealed impaired Paneth and goblet cell differentiation, compromised barrier integrity, heightened epithelial permeability, and increased proinflammatory cytokine levels. Intestinal organoids from mutant mice exhibited amplified cGMP responses to GC-C ligands and defects in secretory lineage specification, confirming cell-autonomous mechanisms. Strikingly, oral zinc administration suppressed aberrant GC-C activity, normalized cGMP levels, and restored barrier function. These findings highlight the central role of epithelial cGMP signaling in coordinating barrier integrity and immune-epithelial interactions and identify zinc as a tractable therapeutic strategy for GC-C-mediated intestinal disorders.NEW & NOTEWORTHY Activating mutations in GUCY2C, which encodes the receptor guanylyl cyclase C (GC-C), cause early-onset diarrheal disease and gastrointestinal inflammation. Knock-in mice carrying a familial diarrheal syndrome mutation exhibited impaired gut barrier function. Mutant organoids showed defective secretory lineage specification associated with reduced Wnt3 expression. Zinc administration, which lowers epithelial cGMP levels by inhibiting GC-C, reversed most pathological changes in both mice and organoids.
  • Journal article
    Schlenker P, Lamberton J, Lan N, Lamberton J, Geraci C, Salis A, Ravaux L, Grüter C, Ryder RJ, Chemla Eet al., 2026,

    Ancestral iconicity: the dance language of bees revisited.

    , Biol Rev Camb Philos Soc, Vol: 101, Pages: 2033-2052

    The waggle dance of bees has given rise to some of the most striking and detailed studies of animal communication. But because of its gradient character, the waggle dance has widely been taken to have properties that are wholly distinct from those of human language. We argue that this is mistaken, and that the waggle dance represents the oldest instantiation of an iconic system also found in human language, notably in sign language. The waggle dance helps bees locate a food source through four properties: (1) food distance is conveyed through the duration of the waggling phase; and (2) food direction is conveyed through the orientation of the waggle run. In addition, (3) while in bees that dance horizontally, the waggle run points towards the food source, in bees that dance vertically the information involves transposition: the angle of the dance relative to 'upwards' is interpreted as the angle of the food direction relative to the sun. Finally, (4) the number of waggle runs increases with food quality. We show that properties 1 and 2 are instantiated in sign language classifier predicates, highly iconic constructions that produce visual animations of the orientation and movement of an entity. Furthermore, classifier movement (property 3) can be interpreted either directly or with 'viewpoint shift', a more flexible version of transposition. Property 4 seems to be instantiated more generally in the pragmatics of human and animal communication, as repetition can convey intensification and/or excitement (e.g. Go, go, go!). We further show experimentally that properties 1-3 are instantiated in some gestures understood by non-signers. Thus the waggle dance is a primitive form of a semantic system also found (through convergent evolution) in human language. It is remarkably ancient, at least 20 million years old according to phylogenetic reconstructions. While the horizontal dance (without transposition) is usually thought to be ancestral, a closer look at extant phyloge
  • Journal article
    Urban MC, Zurell D, Bocedi G, Gonzalez A, Velazco SJE, Bezeng BS, Briscoe NJ, Brotons L, Buckley LB, de Oliveira Junior AC, Cooke R, da Cunha Godoy L, De Marco Júnior P, Eddy TD, Ferrier S, Guillera-Arroita G, Isaac NJB, Krug CB, Lundquist CJ, Mamede M, Metzger JP, Millette KL, Ortega-Cisneros K, Purvis A, Sarmento Cabral J, Settele J, Travis JMJ, Villalobos F, Winter M, Xu Het al., 2026,

    A global research coordination programme is urgently needed for biodiversity.

    , Nat Ecol Evol, Vol: 10, Pages: 1386-1388
  • Journal article
    Stegemann A, Liu S, Retana Romero OA, Oswald MJ, Han Y, Beretta CA, Gan Z, Tan LL, Wisden W, Gräff J, Kuner Ret al., 2026,

    Author Correction: Prefrontal engrams of long-term fear memory perpetuate pain perception.

    , Nat Neurosci, Vol: 29
  • Journal article
    Windram F, Kelly S, Modrak S, Dietrich I, Minetti C, Mansfield KL, Seelig F, Fisher AM, Vollans M, Billows N, Ahmed F, Shocket M, Campino S, Tytheridge S, Gandy SL, Gonzalez E, Medlock JM, Baylis M, Hughes GL, Ewing DA, Purse BV, Kirby G, Strode C, Folly AJ, Starns D, Ferguson H, Smith-Mullally S, Roberts H, Jones CM, Vineer HR, England M, Sanders C, Pawar S, Pearse WD, White SM, Jones RT, Cator LJet al., 2026,

    Come together: Data sharing to support one health responses to vector-borne disease threats.

    , Med Vet Entomol

    Vector-borne diseases (VBDs) are an increasing threat to animal and human health worldwide. Due to the complexity of VBD transmission and ecology, informing responses to VBDs can be challenging. A One Health approach provides a powerful framework for addressing these threats, but its effectiveness depends on timely access to and integration of diverse and often fragmented data categories. Here we outline three key community actions: applying global metadata and data standards, depositing data into global repositories and responsible shared data usage, which can enhance VBD data sharing. We highlight how these data-sharing practices allow for the development of new informatic infrastructure, established by the One Health VBD Hub project, to facilitate analyses and ultimately enhance our ability to provide timely responses to endemic and emerging VBD threats.
  • Journal article
    Balducci MG, Duffy KJ, 2026,

    Interplay between abiotic conditions and mycorrhizal abundance determines differentiation and potential adaptation in a Mediterranean orchid.

    , Ann Bot

    BACKGROUND AND AIMS: Disentangling the relative influence of abiotic and biotic factors on plant population differentiation remains a major challenge in evolutionary ecology yet is essential for understanding the drivers of local adaptation. Orchids are suitable for addressing this question since they often occur in patchily distributed populations, and all orchids depend on orchid mycorrhizal (OrM) fungi for seed germination and establishment. Hence, local abiotic conditions together with OrM fungi may influence population differentiation and adaptation. METHODS: Based on 316,952 polymorphic SNPs sampled from 21 populations across the central Mediterranean range of Orchis italica Poir., we performed a suite of analyses to test how population differentiation and potential adaptation are influenced by the interplay between abiotic factors and OrM fungi. Outlier detection and functional annotation were performed on a subset of SNPs aligned to the Ophrys sphegodes Mill. reference genome. RESULTS: We found strong differentiation at the regional level, while loci under selection were associated with temperature, precipitation regime, soil texture, and the abundance of specific OrM fungal taxa. Functional annotation revealed that outlier SNPs were enriched for genes involved in transcription and RNA processing, signal transduction, stress response and metabolic processes, including in the presence of OrM fungi. CONCLUSIONS: Abiotic conditions and OrM fungi jointly determine differentiation in O. italica. Identifying the selective pressures underlying differentiation and adaptive variation is critical for understanding plant responses to ongoing environmental change.
  • Journal article
    Hobbs B, Limmer N, Clenshaw GL, Ossa F, Karamanos TKet al., 2026,

    Accurate interdomain contacts in a mixed folded protein from NMR-guided coarse-grained simulations.

    , Phys Chem Chem Phys, Vol: 28, Pages: 17194-17202

    Intrinsically disordered, low-complexity regions frequently cooperate with folded domains to mediate protein-protein interactions, yet accurately describing these mixed folded-disordered systems remains challenging. To visualize these mixed folded proteins, experimentally guided coarse-grained (CG) molecular dynamics simulations are often employed to extend the timescales required to capture the complex dynamics in play. However, the minimalistic nature of these approaches often compromises structural accuracy and can lead to inaccurate inter-domain interactions. Here we introduce backbone dihedral terms directly derived from NMR chemical shift data in CG-simulations to characterize the open state of a mixed-folded construct of the anti-aggregation chaperone DNAJB6 that contains a folded J-domain and a disordered GF linker. By tuning residue-specific backbone dihedral parameters to match NMR-derived secondary-structure propensities of the linker in CG-simulations, we generate conformational ensembles that yield accurate interdomain contact maps. In agreement with analysis of NMR relaxation data, the resulting ensembles show that even in the nominally open state the linker experiences motions that resemble those of the closed state driven by hydrophobic residues in GF. More generally, we show that by expanding CG-simulations to allow them to capture both local and global structural properties, physically relevant interdomain contacts can be retrieved.
  • Journal article
    Meramveliotakis E, Ntatsopoulos K, Vogler AP, Papadopoulou Aet al., 2026,

    Association with dynamic habitats disrupts speciation and reduces the efficacy of purifying selection in flightless beetles.

    , Evolution

    Association with temporally dynamic habitats has been proposed as a strong predictor of effective population size (Ne) and speciation rates, and thus also potentially of molecular evolution rates, but empirical insights remain limited. We use a genomic dataset of over 2,000 single-copy orthologs to evaluate how habitat association shapes molecular evolution in closely related flightless beetle lineages (Coleoptera: Tenebrionidae: Eutagenia), co-distributed across Eastern Mediterranean islands. The focal taxa occupy either dynamic coastal sand dunes or stable compact-soil habitats but share uniform life-history traits and morphology. Species delimitation analyses identified a single widespread coastal dune species, whereas the stable-habitat clade has diversified into nine allopatric species across the same geographic space and timeframe. Despite its wide distribution, the dynamic-habitat lineage exhibits the lowest long-term Ne and accordingly the highest mean nonsynonymous-to-synonymous substitution rate ratio (dN/dS), yet its total substitution rate is not significantly higher. We propose that recurrent local population extinction in dynamic habitats hinders the completion of speciation and reduces the efficacy of purifying selection, thus elevating the dN/dS ratio. More broadly, these findings indicate that diversification and molecular evolution rates may become decoupled under recurrent population turnover, a hypothesis that requires further empirical and theoretical investigation.
  • Journal article
    Bernardini F, 2026,

    Sex-ratio distorters enable pre-zygotic sexing for sex-specific transcriptomics in Anopheles gambiae embryos

    , Cell reports, ISSN: 2211-1247

    The study of sex establishment at the onset of development is difficult due to the absence of early morphological differences between male and female embryos. This challenge is particularly relevant in non-model organisms such as the malaria mosquito Anopheles gambiae, where sex determination mechanisms are not fully understood. We employed a pre-zygotic sexing (PZS) system based on synthetic sex-ratio distorters (X- and Y-shredders) to generate large-scale male or female biased embryo populations. Combining the PZS system with a hybrid long- and short-read RNA sequencing, we produced a comprehensive sex-specific transcriptomic dataset of early An. gambiae embryogenesis. Comparative analysis identified four sex-specific spliced genes interacting with the sex-determination network, providing candidates for future functional investigation. Together, the PZS system and sex-specific transcriptomic dataset provide a platform for dissecting early sex differences in An. gambiae, advancing both fundamental understanding of insect sex determination and informing novel vector control strategies.
  • Journal article
    Frankel G, 2026,

    Design of a live-attenuated bacterial vaccine using effector network engineering

    , Nature Communications, ISSN: 2041-1723
  • Journal article
    Bozkurt O, Ecevit A, Gunlemez A, 2026,

    Noninvasive acoustic evaluation of oral feeding skills in preterm infants with bronchopulmonary dysplasia.

    , Pediatr Res

    BACKGROUND: Oral feeding difficulties are common in infants with bronchopulmonary dysplasia (BPD) and contribute to delayed discharge. The aim was to evaluate oral feeding skills (OFS) and swallow-respiration coordination in infants with BPD using a bedside noninvasive signal-based device. METHODS: Prospective observational study. Forty-six infants with BPD and 51 stable preterm controls ( ≤ 32 weeks' gestation) underwent a two-minute oral feeding evaluation. Acoustic swallow and respiratory signals were synchronously recorded to derive total swallow count (TSwC), maximum rhythmic swallow count (MxRSwC), average time between rhythmic swallows (AvgTmBtwnRhSw), respiration rate, and swallowing apnea. RESULTS: Infants with BPD had fewer TSwC and MxRSwC, and a longer AvgTmBtwnRhSw (all p < 0.05). Oxygen desaturation events were more frequent and swallowing apnea was more common in BPD group (%39 vs %9.8, p = 0.001). Infants with BPD achieved full independent oral feeding at an older postmenstrual age than controls. CONCLUSION: Oral feeding skills in preterm infants with BPD are characterized by delayed progression and altered swallowing rhythmicity, suggesting impaired swallow-respiration coordination. Individualized noninvasive acoustic assessment provides a feasible and objective method for the evaluation of OFSs in infants with BPD. IMPACT: Infants with BPD often have delayed and less mature oral feeding skills mostly driven by impaired swallow-respiration coordination. This study demonstrates the feasibility of a simple, objective, noninvasive bedside approach for assessment of swallowing physiology and swallow-respiration coordination during oral feeding. Individualized evaluation of feeding readiness using noninvasive, easily accessible tools may support targeted feeding strategies in preterm infants with BPD.
  • Journal article
    Bourne A, Amatiello FG, Elger K, Roberts KE, Evison SEF, Graystock P, Hughes WOHet al., 2026,

    Feeding the disease: The impact of nutritional supplementation on Nosema (Vairimorpha) infection in honey bees (Apis mellifera).

    , J Invertebr Pathol, Vol: 219

    Honey bees (Apis mellifera) experience variable colony losses across regions and years, with infectious diseases representing a key component of colony health challenges. Among the most prevalent pathogens are the microsporidian parasites Nosema apis and Nosema ceranae, whose impacts on host survival and transmission vary widely depending on context. While nutritional supplementation is commonly used to support honey bee health, its effects on Nosema infection outcomes remain unclear. Here, we experimentally tested whether dietary enrichment alters survival and infection intensity following exposure to a mixed Nosema inoculum. Newly emerged worker bees were challenged with Nosema spores and maintained on either a basic sucrose diet or the same diet supplemented with a commercial pollen substitute. Dietary enrichment significantly increased both mortality risk and infection intensity in Nosema-infected bees, while having no detectable effect on survival in uninfected controls. These results indicate that supplementation can, counter intuitively, exacerbate nosemosis by promoting parasite replication rather than enhancing host resistance. Our findings highlight the importance of distinguishing nutritional effects on host tolerance versus resistance, and caution that interventions intended to improve bee nutrition may inadvertently increase pathogen production and transmission potential under certain conditions.
  • Journal article
    Ogwang R, Nkumama IN, Mwai K, Odera D, Nyamako L, Fürle K, Rosenkranz M, Kimathi R, Njuguna P, Sim BKL, Hamaluba M, Frank R, de Laurent Z, Kariuki S, Kimani D, Mohammed KS, Mosobo M, Abdi AI, Omuoyo D, Otieno E, Shangala J, Wambua J, Musembi J, Musyoki J, Muthui M, Mwacharo J, Ndungu F, Ngoi JM, Makale J, Ogwang R, Ngoto O, Odera DO, Abebe Y, Richie TL, Billingsley PF, Hoffman SL, James ER, Osier FHA, Marsh K, Ongecha J, Bull PC, Kinyanjui S, Kivisi C, Ogutu B, Olewe F, Williams TN, Kapulu MC, Bejon P, Tuju J, Osier FHAet al., 2026,

    Controlled human malaria infection in adults identify combinations of merozoite antigens associated with clinical immunity

    , Nature Communications, Vol: 17, ISSN: 2041-1723

    Two vaccines are currently licensed against Plasmodium falciparum malaria but offer only partial protection that wanes, necessitating repeated dosing that is challenging to implement where it is needed most. We previously identified a subset of Kenyan adults with naturally acquired clinical immunity using controlled human malaria infection studies (CHMI, n = 86/142; ClinicalTrials.gov - NCT02739763). Subsequent studies showed that clinical immunity was strongly correlated with IgG Fc-mediated functional activity against whole merozoites. Here, to zoom in on specific targets associated with clinical immunity, we use samples from the CHMI study and a custom protein microarray (KILchip) to measure IgG antibody reactivity against seventy recombinant merozoite antigens. We identify the top-ranking antigens by analyzing the data using five distinct statistical methodologies: the nonparametric Wilcoxon rank sum test, a Cox proportional hazards model, a modified Poisson regression model, and the machine learning Least Absolute Shrinkage and Selection Operator (LASSO) and random forest models. Antibodies against MSP1, MSP11, RAMA, MSP7, PF3D7_1401600 (PHISTB) and PTEX150 were consistently associated with clinical immunity and in combination predicted complete protection. These findings may be useful to prioritize the next generation of malaria blood stage vaccine candidates.
  • Journal article
    Song G, Ma Z, Fan M, He L, Lan Y, Li W, Jiang Z, Jiang Q, Noone DP, Nans A, Nahas KL, Barkestani MN, Wang S, Wang Q, Ren P, Cheng J, Zang Y, Zhou H, Johnson J, Mullan C, Gong X, Bubeck D, Moeckel G, Mak M, Tellides G, Jane-Wit Det al., 2026,

    Internalized components of membrane attack complexes disrupt proteostasis and acquire alarmin-like properties.

    , Nat Commun

    Immune effects of membrane attack complexes (MAC) have been widely attributed to their abilities to cause cell death. Here, we show that the MAC component, C9, forms non-cytolytic aggregates with pro-inflammatory effects. Intracellular aggregates of C9 are detected within inflamed tissues of patients in association with endothelial cell (EC) activation but not increased cell death. We identify NUMBL as a Rab35 effector that directly binds surface-bound C9 to promote C9 internalization and entry into the endolysosomal pathway. Within acidified endolysosomes, C9 forms insoluble aggregates that are targeted for degradative aggrephagy in a process that activates NF-κB. For C9 aggrephagy to occur, ZFYVE21, a Rab5 effector, complexes with RNF34 to bridge C9 aggregates to LC3B+ aggresome membranes. We detect C9 aggregates in vivo, and we show that a ZFYVE21-RNF34 signaling axis is required for C9 aggrephagy and NF-κB -dependent EC activation in three separate mouse models. Mice with conditional loss of ZFYVE21 in ECs show reduced aggregraphy, resulting in attenuated systemic inflammation and reduced tissue injury following skin transplantation. Our data show that the C9 component of MACs forms intracellular aggregates with alarmin-like properties.
  • Journal article
    Nematbakhsh M, Koufopanou V, Cass A, Burt Aet al., 2026,

    Genomic characterisation and diversity of dsRNA viruses and their killer satellites in a natural population of the yeast <i>Saccharomyces paradoxus</i>

    , Virus Evolution

    <jats:title>Abstract</jats:title> <jats:p>Killer yeasts secrete protein toxins that inhibit other yeast strains, a trait often encoded by M satellites of L-A dsRNA viruses. These systems serve as important molecular models, yet their adaptive significance in natural settings remains unclear. This study surveyed 60 strains from a natural Saccharomyces paradoxus population in the UK to characterise dsRNA viral genomic diversity. Our survey revealed 27% of strains showed killer activity mediated by dsRNA viruses. Additionally, five of 18 non-killer strains also contained dsRNA viruses. Deep sequencing of pooled dsRNAs from 17 strains identified six distinct M satellite types, including three novel lineages, with single nucleotide and structural polymorphisms creating multiple variant sequences within types. Predicted preprotoxin proteins generally contained post-translational modification sites necessary for toxin maturation, although with variable numbers among different types, potentially affecting processing and expression. Eight L-A virus sequences were also assembled. These were all closely related to each other and clustered phylogenetically with viruses from other European S. paradoxus strains. Extended 5′ sequence analysis revealed novel structural features in both L-As and their M satellites, including a pair of inverted repeats ending in a pair of inverted conserved motifs (GA5–6 and corresponding U5–6C in Ms and GAAUA and corresponding UAUUC in L-As) which is in turn flanked by a pair of direct repeats. The pair of conserved motifs also exists in all described Saccharomyces cerevisiae M satellites. The observed diversity of dsRNA satellites within a single yeast population is a challenge to explain, with many evolutionary forces potentially contributing.</jats:p>
  • Journal article
    Endres R, 2026,

    The unreasonable likelihood of being: origin of life, terraforming, and AI

    , npj Systems Biology and Applications, ISSN: 2056-7189

    The origin of life on Earth via the spontaneous emergence of a protocell prior to Darwinian evolution remains a fundamental open question in physics and chemistry. Here, we develop a conceptual framework based on information theory and algorithmic complexity. Using estimates grounded in modern computational models, we evaluate the difficulty of assembling structured biological information under plausible prebiotic conditions. Our results highlight the formidable entropic and informational barriers to forming a viable protocell within the available window of Earth’s early history. While the idea of Earth being terraformed by advanced extraterrestrials might violate Occam’s razor from within mainstream science, directed panspermia—originally proposed by Francis Crick and Leslie Orgel—remains a speculative but logically open alternative. Ultimately, uncovering physical principles for life’s spontaneous emergence remains a grand challenge for biological physics.
  • Journal article
    Godson A, Eddie L, Schuster M, Zheng K, Toth R, Li Y, Li T, Huang J, Kaschani F, Jutras PV, Kourelis J, Kaiser M, Bozkurt T, Van der Hoorn RALet al., 2026,

    NbRD21 protease controls receptor kinase homeostasis in Nicotiana benthamiana.

    , New Phytol

    RD21-like proteases are papain-like cysteine proteases with a C-terminal granulin domain that are abundant and ubiquitous in angiosperms and have often been implicated in immunity. We previously found that the activity of RD21 in Nicotiana benthamiana (NbRD21) is suppressed during infection with Pseudomonas syringae. Here, we studied the role of NbRD21 in immunity and proteome processing. NbRD21 was disrupted by genome editing and rd21 mutants were subjected to disease assays and shotgun proteomics. Dipeptide substrate zLR-AMC was used in protease assays and agroinfiltration was used to transiently express NbRD21 and candidate substrates. Genome-edited lines lacking NbRD21 develop normally but have drastically reduced zLRase activity and are significantly more susceptible to P. syringae. Shotgun proteomics revealed an increased accumulation of c. 20 diverse receptor-like kinases (RLKs) in untreated rd21 knockout lines, but their transcript levels are unaltered when compared to wild-type plants. 35S-driven GFP-tagged RLKs accumulate more upon transient expression in rd21 plants than in wild-type plants. These data indicate that NbRD21 post-translationally controls RLK homeostasis, either by directly degrading RLKs or indirectly by regulating endocytic RLK recycling.
  • Journal article
    Ghosh M, Goodman D, 2026,

    Partial recurrence can enable robust and efficient computation

    , Communications AI and computing, ISSN: 3091-292X

    Neural circuits are sparse and bidirectional. Meaning that signals flow from early sensory areas to later regions and back. Yet, between connected areas there exist some but not all pathways. How does this structure, somewhere between feedforward and fully recurrent, shape circuit function? To address this question, we designed a recurrent neural network model in which a set of weight matrices (i.e. pathways) can be combined to generate every network structure between feedforward and fullyrecurrent. We term these architectures partially recurrent neural networks (pRNNs). We trained over 25,000 pRNNs on a novel set of reinforcement learning tasks, designed to mimic multisensory navigation, and compared their performance across multiple functional metrics. Our findings reveal three key insights. First, in dense-cue environments, most pRNN architectures match or exceed the task performance, learning speed or robustness of fully recurrent networks, despite using as few as one quarter the number of parameters; in sparse-cue environments, many match but a substantial fraction underperform. These results demonstrate that partial recurrence can enable energy efficient, yet performant solutions. Second, each pathway’s functional impact is both task and circuit dependent. For instance, feedback connections enhance robustness to noise in some, but not all contexts. Third,different pRNN architectures learn solutions with distinct input sensitivities and memory dynamics, and these computational traits help to explain their functional capabilities. Overall, our results demonstrate that partial recurrence can enable robust and efficient computation- a finding that may help to explain why neural circuits are sparse and bidirectional, and shows how these principles can inform the design of artificial systems.
  • Journal article
    Lau R, Giblin S, Sugar A, Di Maio A, Tassinie G, Huse K, Chorev D, Chen Y, Wu G, Berg Huemer C, Seung YK, Matthewsa J, Muloud B, Chen L, McKenna S, Xu Y, Massai L, Muzzie C, Ferhatie X, Necchie F, Gomes Moriel D, Feizi T, James P, Sriskandan S, Matthews Set al., 2026,

    SpyCEP dismantles neutrophil immunity via disorder-drivenchemokine remodeling and GAG targeting

    , Proceedings of the National Academy of Sciences of the United States of America, ISSN: 0027-8424

    Streptococcus pyogenes (Group A Streptococcus; GAS) employs sophisticated virulence strategies to evade human immunity, including secretion of the cell envelope protease SpyCEP, which cleaves and inactivates key neutrophil‑attracting chemokines such as CXCL8. Here, we integrate cryo‑electron microscopy (cryo‑EM), nuclear magnetic resonance (NMR) spectroscopy, and native mass spectrometry (MS) to investigate how SpyCEP disrupts CXCL8 function. We demonstrate that a disordered aromatic and acidic region within the cleaved autocatalytic maturation loop (CAML) of SpyCEP mimics receptor N-domains and binds an allosteric site on CXCL8. The resulting interaction forms a dynamic fuzzy complex and is coupled to dimer dissociation, consistent with enhanced access to the cleavage site. This disorder‑mediated substrate engagement differs from classical protease mechanisms that rely on rigid recognition interfaces. Additionally, glycan microarray and NMR analyses show that the CAML region mediates glycosaminoglycan (GAG) binding, suggesting a means to recruit SpyCEP and maximize encounters with GAG‑enriched CXCL8 reservoirs. Together, these findings provide a structural and biophysical framework for understanding how SpyCEP combines substrate engagement with GAG targeting to dismantle chemokine gradients and inhibit neutrophil recruitment. More broadly, this work highlights the role of intrinsic disorder in protease recognition and suggests new avenues for anti‑virulence therapies and vaccine strategies targeting SpyCEP.

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