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Journal articleBruno F, Langhorne J, Lo Celso C, 2026,
Protocol for repeated Plasmodium chabaudi infection in a murine malaria model
, STAR Protocols, Vol: 7, ISSN: 2666-1667In malaria-endemic regions, individuals experience repeated malaria infection throughout life. Here, we present a protocol to investigate the immunological mechanisms triggered by repeated exposure using a murine model of sequential infections with the rodent parasite Plasmodium chabaudi chabaudi. We provide a detailed and standardized series of steps covering primary infection, natural recovery without treatment, and subsequent secondary infection. This approach offers a robust framework to investigate the effects and long-term consequences of repeated malaria infections on the host.
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Journal articledos Anjos L, Farneda FZ, Medeiros HR, et al., 2026,
Functional trait space overlaps reveal ecological resilience of bird communities in Atlantic Forest fragments
, Biological Conservation, Vol: 324, ISSN: 0006-3207While fragmentation is known to affect species diversity, the degree to which functional structure is retained relative to primary forests and the factors driving this retention remain poorly understood. Here, we applied the concept of ecological resilience to forest fragmentation by examining the extent to which bird communities in 20 forest fragments (27-926 ha) retain the functional trait space observed in a large, protected area of primary forest used as a reference, Iguaçu National Park (INP), within the Seasonal Semideciduous Atlantic Forest of southern Brazil. We used retention of the functional trait space of the reference forest as an indicator of potential ecological resilience and, consequently, conservation value. Functional trait spaces were estimated using kernel hypervolumes, and three metrics were calculated: (1) the percentage overlap between the trait spaces of INP and each fragment; (2) the fraction of trait space unique to INP; and (3) the fraction unique to each fragment. Functional overlap ranged from 63 to 77%, the fraction unique to INP ranged from 5 to 29%, and the fraction unique to fragments ranged from 14 to 24%. Although observed functional overlap was substantial, it did not differ significantly from null expectations based on species richness and abundance structure. Landscape diversity is associated with a higher percentage of trait space unique to fragments, whereas larger fragment area was associated with greater overlap in trait space between INP and fragments. Assessing trait space overlap between continuous forest and fragments provides a novel perspective on functional responses to fragmentation and can help identify patterns potentially relevant to ecosystem functioning.
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Journal articleYuen ELH, 2026,
A splicing checkpoint couples surface and intracellular plant immunity
, Phytopathology Research, Vol: 8, ISSN: 2096-5362Plant immunity operates through two interconnected layers. Pattern-triggered immunity (PTI) is initiated by cell-surface pattern-recognition receptors, whereas effector-triggered immunity (ETI) is executed by intracellular nucleotide-binding leucine-rich repeat (NLR) receptors. The two layers are known to potentiate one another, yet how a signal perceived at the plasma membrane is relayed to prime an intracellular NLR has remained unclear. In a recent study, Gao et al. (2026) show that the potato late blight resistance protein Rpi-vnt1.1 carries a self-imposed restraint, an autoinhibitory N-terminal extension encoded by an intron-retained mRNA isoform. Pathogen perception, acting through PTI, shifts the balance of alternative splicing towards an isoform that lacks this extension, producing a resistosome-competent receptor that the Phytophthora infestans effector AVRvnt1 can then activate. This work defines pre-mRNA alternative splicing as a checkpoint that couples surface and intracellular immunity, and points to a broadly conserved and engineerable mode of NLR control.
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Journal articleMaia RA, Oki Y, Medina I, et al., 2026,
Atlantic forest tree enhances photoprotective and thermotolerance in soils contaminated by mining tailings
, Theoretical and Experimental Plant Physiology, Vol: 38Large-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.
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Journal articleHui T-Y, Epopa PS, Millogo AA, et 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: 1756-3305Background 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
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Journal articleWan Y, Wong JLC, Sanchez-Garrido J, et 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: 2730-6844Background 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
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Journal articlePashley SL, Hair M, Ukegbu CV, et al., 2026,
Plasmodium protein kinase 2 is required for ookinete-to-oocyst transition and parasite transmission.
, Life Sci Alliance, Vol: 9Plasmodium parasites rely on diverse protein kinases to regulate critical processes, yet many remain uncharacterised. Protein kinase 2 (PK2) is required for asexual blood-stage proliferation and merozoite invasion, but its role in sexual stages and transmission is unknown. Here, using live-cell and super-resolution imaging, ultrastructural analysis, functional phenotyping, and quantitative phosphoproteomics, we define the role of PK2 in Plasmodium berghei transmission. PK2 was expressed in merozoites, ookinetes, and sporozoites: the three invasive forms of the parasite. Conditional depletion of PK2 impaired ookinete motility, disrupted apical microneme positioning, abolished oocyst formation, and prevented mosquito-to-host transmission. Direct haemocoel injection of mutant ookinetes failed to restore sporozoite production, demonstrating an additional requirement for PK2 downstream of midgut traversal. Although global protein abundance was largely preserved, phosphoproteomic profiling identified altered phosphorylation of proteins associated with cytoskeletal organisation, host-cell interaction, midgut invasion, and gene regulation. These findings highlight PK2's critical role across multiple invasive stages, advancing understanding of malaria parasite transmission and identifying putative PK2-regulated pathways as potential targets for transmission-blocking interventions.
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Journal articleDe Lorm TA, Heon SP, Bernard H, et al., 2026,
Bird and mammal communities transform without collapsing in response to oil palm replanting
, Forest Ecology and Management, Vol: 619, ISSN: 0378-1127Replanting 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.
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Journal articleBourne A, Amatiello FG, Elger K, et al., 2026,
Feeding the disease: The impact of nutritional supplementation on Nosema (Vairimorpha) infection in honey bees (Apis mellifera).
, J Invertebr Pathol, Vol: 219Honey 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.
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Journal articleArnell M, Suggitt AJ, Antão LH, et al., 2026,
Interacting Effects of Climate and Land Use on Biodiversity: A Guide to What They Are and Why They Matter
, Global Ecology and Biogeography, Vol: 35, ISSN: 1466-822X<jats:title>ABSTRACT</jats:title> <jats:sec> <jats:title>Problem</jats:title> <jats:p>Climate and land‐use change are two key drivers of biodiversity change. Their widespread effects on species and communities have prompted fears that interactions between the two drivers could cause severe biodiversity loss. As the literature on this subject expands rapidly, variation in methodological choices and the terminology used to describe results, combined with context‐dependent or individualistic responses across taxa and systems, hinders our ability to systematically evaluate how species and communities are affected by the interacting effects of climate and land‐use change.</jats:p> </jats:sec> <jats:sec> <jats:title>Clarification</jats:title> <jats:p>We provide guidance for investigating climate‐land‐use interactions, following clear definitions and including recent examples from natural and semi‐natural systems. We highlight how variation in methodologies, language inconsistencies, data limitations, and the inherent variation among populations and species can affect the analysis of climate‐land‐use interactions. Importantly, we demonstrate how failing to consider interactive effects can negatively impact the outcomes of conservation interventions designed to protect biodiversity.</jats:p> </jats:sec> <jats:sec> <jats:title>Communicating Climate‐Land‐Use Interactions</jats:title> <jats:p>We provide a roadmap to guide future work, highlighting important considerations for understanding and communicating climate‐land‐use interactions relevant for both policy and conservation. Outlining how different factors can complicate our understanding of interactive effects is a key s
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Journal articleLombardi P, Ramon-Gil E, Raja RQ, et al., 2026,
A myeloid immunosuppressive phenotype defines primary refractoriness to atezolizumab plus bevacizumab in hepatocellular carcinoma.
, J Hepatol, Vol: 85, Pages: 899-911BACKGROUND & AIMS: Despite improved outcomes with atezolizumab plus bevacizumab (A+B) in hepatocellular carcinoma, primary refractoriness (PRef), characterised by early progression or short-lived disease stabilisation following treatment, remains a significant challenge. METHODS: We analysed 1,296 patients with hepatocellular carcinoma treated with frontline A+B (AB-real) and validated findings in 645 trial participants recruited to IMbrave150 and GO30140. PRef was defined by SITC (Society for the Immunotherapy of Cancer) criteria. We performed a multi-parametric analysis of pre-treatment tumour tissue, including machine learning-based quantification of tumour-infiltrating lymphocytes, imaging mass cytometry and RNA sequencing (RNA-seq) to evaluate differences in the tumour microenvironment (TME) of patients with PRef vs. responders. Two independent cohorts were further used to refine the TME characterisation through single-cell RNA-seq (n = 20) and imaging mass cytometry (n = 16). We employed conditional inference tree analyses to provide a hierarchical organisation of PRef determinants. RESULTS: Among 677 AB-real patients and 378 trial participants evaluable by SITC criteria, PRef was associated with inferior median overall survival compared to response (AB-real: 7.3 vs. 31.5 months, p <0.001; Trials: 10.8 vs. not reached, p <0.001). Patients with PRef exhibited higher baseline systemic inflammation (neutrophil-to-lymphocyte ratio [NLR] ≥3), a distinctly immunosuppressive TME enriched in CD163+ tumour-associated macrophages and vascular cancer-associated fibroblasts, a higher Treg/Teff cell ratio, and pro-tumour supportive cellular interactions. RNA-seq of tumour tissue confirmed lower intrinsic immunogenicity in PRef samples with elevated myeloid infiltration. Conditional inference tree analysis identified IFN-γ signature downregulation combined with NLR ≥3 as the strongest contributor of PRef. CONCLUSIONS: PRef to A+B identifies a distinct
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Journal articleBrook TS, ODonovan M, Hutton IJ, et al., 2026,
Germination behaviour and desiccation tolerance of <i>Coprosma</i> (Rubiaceae) seeds from a remote oceanic island
, Seed Science Research, Pages: 1-15, ISSN: 0960-2585<jats:title>Abstract</jats:title> <jats:p> Seed banking can be an efficient approach to conserve plant species <jats:italic>ex situ</jats:italic> . Research into the suitability of long-term seed banking for (sub)tropical species is limited and urgent, especially for taxa with limited distributions such as those endemic to oceanic islands. Here, we combine a stepwise experimental methodology with non-parametric and survival analyses to assess the germination requirements and desiccation tolerance of three species of Currant Bush <jats:italic>Coprosma</jats:italic> (Rubiaceae) from Lord Howe Island, a remote island in the South Pacific. All species germinated best under temperatures equivalent to submontane spring/autumn conditions, consistent with temperatures during ripe fruit dispersal. Although warmer temperatures inhibited germination in all species, the species with the broadest elevational range was the least affected. Consistent with the wider literature, we found a negative relationship between seed size and drying tolerance, with the larger seeds of <jats:italic>Coprosma huttoniana</jats:italic> and <jats:italic>C. ptotopetra</jats:italic> sensitive to the drying required for conventional seed banking, while the smaller seeds of <jats:italic>C. lanceolaris</jats:italic> were tolerant and potentially bankable for long-term conservation. </jats:p>
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Journal articleIvars J, Gurung J, Gispert I, et al., 2026,
Decorating bacteria with electrostatically bound liposomes as programmable extracellular functional compartments
, ISSN: 2198-3844Living cells are powerful programmable systems, yet efforts to engineer them are limited by the constraints of genetic modification, including metabolic burden, restricted chemical diversity of biomolecular systems, and slow, gene expression–driven responses. Complementary approaches augmenting cells without altering their genome offer an attractive route to expand their functionality. Here, we establish a strategy for equipping bacteria with synthetic extracellular organelle-like compartments by electrostatically assembling liposomes onto the surface of Escherichia coli. This approach yields stable, multi-compartment, high-density coatings without genetic or covalent modification, while preserving bacterial growth, gene expression, and motility. We show that these surface-bound liposomes can function as modular ompartments that operate alongside the cell, enabling capabilities that are difficult to realize genetically, including thermoresponsive cargo release and abiotic catalytic activity. Together, this work shows that bacteria–liposome biohybrids can be engineered with appended, tunable synthetic compartments to expand the functional repertoire of living cells.
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Journal articleDrickamer K, Jegouzo S, Feinberg H, et al., 2026,
Glycan-mediated binding to collagen by a C-type lectin-like domain of the endocytic receptor Endo180 / uPARAP
, Journal of Biological Chemistry, ISSN: 0021-9258The primary role of the multidomain endocytic receptor designated Endo180 or uPARAP (urokinase-plasminogen activator receptor associated protein) is to facilitate internalization of collagen for lysosomal degradation during matrix remodeling in tissues. However, Endo180 interacts both with collagen and sugars and the relationship between these activities is not fully defined. While collagen-binding activity is associated with a fibronectin type 2 domain and an adjacent C-type lectin-like domain 1 (CTLD1), sugar-binding activity resides in CTLD2. Potential interactions of CTLD2 with various glycans have been examined by glycan array screening, solid phase binding assays, x-ray crystallography, and molecular modeling. Glycan array screening suggests potential interactions with exposed GlcNAc residues on truncated core 2 and core 4 O-linked glycans, but such structures are rare. Binding competition assays demonstrate that the disaccharide Glcα1-2Gal, found attached to hydroxylysine residues in collagens, is an alternative ligand. X-ray crystallography analysis of a complex of α-methyl fucoside with CTLD2 provides a basis for modeling how the Glcα1-2Gal disaccharide attached to hydroxylysine can be accommodated in the binding site with both sugar residues making favorable interactions with the protein. In direct binding studies, types IV and V collagen, but not type I collagen, bind to CTLD2 through the sugar-binding site. These results provide direct evidence that sugar-binding activity of CTLD2 contributes to binding of heavily glycosylated collagens. Although other endogenous mammalian glycan targets for CTLD2 are rare, CTLD2 can additionally interact with pathogen glycans such as poly-N-acetylglucosamine, contributing to the general role of Endo180 as a scavenger receptor.
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Journal articleMaretvadakethope S, Aor I, Fischer MM, et al., 2026,
Let there be multifunctionality: Uncovering the dynamical zoo of the AC-DC genetic circuit.
, Cell Syst, Vol: 17Gene regulatory networks (GRNs) govern many cell processes. While multistability and oscillations are common GRN dynamics, they are typically studied and engineered in isolation. Here, we challenge this separation using the AC-DC circuit, a minimal three-gene network that merges the classical toggle switch and repressilator. Using a thermodynamic formalism and Bayesian inference, we show that a single-inducer version of the circuit displays diverse multifunctional dynamics, including coexistence of oscillations and multistability. We explore robustness, classify emergent behaviors, and analyze critical slowing down. Remarkably, the AC-DC circuit can produce more than thirty topologically distinct bifurcation diagrams, results that challenge the classical view that network topology rigidly constrains dynamical outcomes. This flexibility enables synthetic capabilities coupling hysteresis with oscillations, criticality, and reversibility. By uncovering the potential of minimal genetic circuits and outlining design principles for their implementation, this work opens directions for harnessing emergent complexity using the basic building blocks of life. A record of this paper's transparent peer review process is included in the supplemental information.
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Journal articleDing R, Nobrega R, Collalti A, et al., 2026,
Resolving the multiple controls of biomass productionefficiency in woody plants
, Global Change Biology, ISSN: 1354-1013Plants assimilate carbon through photosynthesis to support biomass production (BP), autotrophic respiration (Ra) and the synthesis of non-structural compounds. Biomass production efficiency (BPE), the fraction of assimilated carbon allocated to BP, is one key factor influencing ecosystems’ potential to store carbon. However there is no consensus on the controls of BPE, and even the sign of its response to growth temperature is unclear. By means of statistical hypothesis testing using the largest observational dataset to date on annual BPE (n = 514 records) from evergreen and deciduous woody plants, we confirm earlier findings that BPE declines with stand age and is greater in deciduous plants. However, we also show that BPE declines towards more organic, sandy, or alkaline soils and increases with climatic aridity, while declining with warmer growing seasons and increasing with warmer winters. Such a dual temperature response is consistent with additional carbon costs due to the need for cold-hardening processes, and reconciles contradictory published reports of both positive and negative effects of temperature on BPE. Notably, our analysis provides novel evidence that BPE is significantly higher in species associated with arbuscular mycorrhizal (AM) fungi than in those associated with ectomycorrhizal (EcM) fungi and mixed EcM–AM associations. Our analysis explains the observed BPE patterns better than dynamic global vegetation models (DGVMs) from the TRENDY (Trends and Drivers of the Regional-Scale Terrestrial Sources and Sinks of Carbon Dioxide) project, which show a weaker correspondence with observations. In particular, our model captures reduced BPE in boreal regions, consistent with the predominance of ectomycorrhizal (EcM) species there. This study advances understanding of the global controls of BPE, and suggests a route towards the improved representation of plant growth in vegetation and land surface models.
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Journal articleSecchi MA, Mai C, Liu Q, et al., 2026,
A new reporter strategy reveals a subset of nonmigratory hematopoietic stem cells located in a dynamic bone marrow niche.
, BloodInteractions of hematopoietic stem cells (HSCs) with the bone marrow microenvironment are critical to regulate stem cell function in homeostasis, emergency hematopoiesis and ageing. The dynamic behavior of endogenous HSCs in their niches has been challenging to study due to the complexity of markers required to define pure HSCs. Multiple recently developed reporter strategies advanced our capacity to identify HSCs in situ. Yet, they provide different levels of HSC enrichment and are frequently not stable in situations of perturbed hematopoiesis, leading to contradictory observations of HSC localization and migratory behavior. Here we employed a new double reporter strategy by combining the Hoxb5-mKO2 and Vwf-GFP reporters, that are stably expressed in homeostasis, stress and ageing. Hoxb5+Vwf+ cells represent a subset of highly pure and potent long-term HSCs with a platelet-biased pattern of differentiation, that are included in the populations identified by other reporter strategies. Intravital microscopy revealed Hoxb5+Vwf+ cells to be non-migratory in homeostasis, ageing, or following acute thrombocytopenia when these cells are actively proliferating, indicating that this non-migratory behavior is independent of cell cycle status. We found Hoxb5+Vwf+ HSCs in perivascular niches with a higher coverage by LepR+ mesenchymal cells but not preferentially located closer to megakaryocytes, when compared to Hoxb5+Vwf- cells. Nevertheless, stress-induced megakaryopoiesis following acute thrombocytopenia bring megakaryocytes into closer proximity of Hoxb5+Vwf+ HSCs, revealing previously unrecognized niche dynamics in HSC regulation during regeneration.
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Journal articlePrakash S, Isalan M, Varela C, 2026,
A genetically encoded local learning rule enables physical learning in engineered bacteria
, Nature Communications, ISSN: 2041-1723 -
Journal articleDollhopf LC, Perrett S, Schatz D, et al., 2026,
Structure-BasedDesign with Arylazopyrazoles to EnableHigh-Affinity Photoswitchable Inhibitors of <i>N</i> -Myristoyltransferase
, Journal ofthe American Chemical Society, ISSN: 0002-7863<jats:title>Abstract</jats:title> <jats:p>Photopharmacology using photoswitches is a powerful way to reversibly control biological function with light, through the generation of photoswitchable synthetic ligands. While optimization of bioactive small molecules is increasingly driven by iterative experimental protein–ligand structures, structure-guided improvement in photoswitch photopharmacology using experimental structures remains rare. Here we report the development of the first photoswitchable inhibitors of the human enzyme N-myristoyltransferase 1 (HsNMT1), using an arylazopyrazole (AAP) as the switch motif. Through experimental structure-based design, we obtain inhibitors with single-digit nanomolar affinity for NMT, functional activity in cells, and good differential activity between E and Z photoswitch isomers. The availability of our highly potent ligands and protein–ligand structures, coupled with the excellent photoswitch properties of the AAP, allowed us to study the effect of protein binding on the switching events, including characterization of protein-bound Z → E photoisomerization kinetics for the first time. Overall, this study showcases the potential for structure-based design in photoswitch pharmacology, including understanding the dynamic consequences of target binding, paving the way for the development of advanced photopharmaceuticals.</jats:p>
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Journal articleGuffick C, Rincon Pabon JP, Griffiths D, et al., 2026,
An Automated HDX−MS Platform for Characterization of Membrane Proteins within Biological Membranes
, Analytical Chemistry, ISSN: 0003-2700<jats:title>Abstract</jats:title> <jats:p>The structural study of membrane proteins has traditionally relied on detergent-based extraction from cellular membranes. Although native-like reconstitution approaches have advanced, fully understanding membrane protein dynamics requires examining them within their native membrane environment. Hydrogen−deuterium exchange mass spectrometry (HDX−MS) is a powerful method for probing structural dynamics in reconstituted systems, but the presence of the lipid bilayer introduces considerable complexity, limiting its broader adoption under physiological conditions. Here, we present the first fully automated HDX−MS platform incorporating a two-stage delipidation workflow. We applied this approach to monitor the dynamics of the ABC transporter MsbA in isolated inner membrane vesicles (IIMVs) from Escherichia coli in its apo and inhibited posthydrolytic states. IIMVs revealed distinct dynamic features within the nucleotide binding domains and substrate binding cavity, highlighting physiologically relevant motions not observed with detergent-solubilized MsbA. This platform significantly advances HDX−MS and underscores the importance of studying membrane proteins in native lipid environments.</jats:p>
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Journal articleTsitsa I, Hanna G, Conev A, et al., 2026,
Missense3D: leveraging protein structures, including AlphaFold models, to understand the effect of missense variants
, Journal of Molecular Biology, Pages: 170066-170066, ISSN: 0022-2836The growing availability of 3D protein structures enables large-scale assessment of missense variants and their phenotypic impact. Missense3D, first developed in 2019, predicts the structural consequences of amino acid substitutions and provides mechanistic explanations by identifying features such as cavities, steric clashes and disrupted non-covalent bonds that may cause protein misfolding.The new Missense3D algorithm presented here accepts genomics, protein, and structural coordinates; models variants on both single proteins and protein-protein complexes using experimental and predicted structures, including AlphaFold models; performs automated sequence-structure mapping; and evaluates structural model quality before analysis. The Missense3D web server is freely available to all users, including commercial ones, at https://missense3d.bc.ic.ac.uk/~missense3d2/.
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Journal articleBradshaw J, Sanchez-Garrido J, David S, et al., 2026,
PgaR is a positive regulator of the pgaABCD biosynthetic operon in Klebsiella pneumoniae.
, Infect Immun, Vol: 94The biosynthetic locus encoding the exopolysaccharide poly-N-acetyl-glucosamine (PNAG) is widely conserved across bacteria, including the World Health Organization critical-priority pathogen Klebsiella pneumoniae (Kp). In Kp, PNAG synthesis is mediated by the pgaABCD operon, yet its lineage-specific regulation remains incompletely understood. Using a comparative genomics approach to interrogate the pgaABCD locus across the high-risk clonal Kp complex 258 (CC258) lineage, we identified a previously uncharacterized positive transcriptional regulator located immediately upstream of pgaA, which we designate pgaR. Phylogenetic analysis revealed recurrent evolutionary events affecting this regulatory region, including repeated deletion or truncation of pgaR and a G > A substitution upstream of the pgaR start codon. Functional characterization demonstrated that loss of pgaR abolishes pgaABCD expression and PNAG production, whereas the upstream G > A substitution drives PNAG hyperproduction. Under in vitro growth conditions, Kp produce extensive extracellular PNAG networks. Using a prototype hypervirulent strain to model the role of PNAG in vivo indicated that it is dispensable for virulence in murine pneumonia and peritonitis models. In contrast, PNAG hyper-production significantly attenuated virulence and reduced disease severity. Collectively, these findings identify PgaR as a novel upstream gene regulator of the pgaABCD operon and reveal a previously unrecognized lineage-specific layer of PNAG regulation in Kp. This demonstrates that opposing PNAG phenotypes, loss and hyper-production, have independently and repeatedly emerged among clinical CC258 isolates, highlighting selective pressures acting on this locus.
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Journal articleNash DA, Barrow HG, Antrobus PR, et al., 2026,
Herpes simplex virus pUL56 abolishes neuronal activity by removing voltage-gated ion channels from the plasma membrane.
, Sci Adv, Vol: 12Herpes simplex virus 1 (HSV-1) infections of the central nervous system cause encephalitis and are associated with increased risk of neurodegeneration, yet the molecular consequences of lytic infection in human neurons remain incompletely defined. We map the transcriptomic, proteomic, and surface-proteome changes induced by HSV-1 across the lytic infection cycle in human induced pluripotent stem cell-derived cortical glutamatergic neurons. HSV-1 drives extensive plasma-membrane remodeling, including the removal of voltage-gated sodium, potassium, and calcium channels, resulting in a profound loss of synchronous calcium signaling. We identify the viral ubiquitin-ligase adaptor pUL56 as the principal effector of this process: pUL56-dependent degradation of ion channels abolishes coordinated calcium signaling, whereas mutation of its E3-ligase-binding motifs preserves synchrony. Furthermore, expression of pUL56 alone is sufficient to abolish neuronal electrical activity. These findings establish pUL56 as a potent viral suppressor of neuronal excitability.
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Journal articleLuo J, Liu L, Yang X, et al., 2026,
Jasmonate biosynthesis regulates key events in barley vegetative and reproductive development.
, New PhytolCereal grain is a global food staple. Filial tissues in grain, such as the embryo and endosperm, grow embedded in the maternal ovule and surrounding ovary wall. Maternal tissues provide nutrition and protection but are progressively reduced and degraded as filial tissues expand, driving grain expansion between floret hulls. While we know some enzymatic players, regulation of this process remains less understood. However, our previous work in barley, Hordeum vulgare spp. vulgare suggested a role for the phytohormone jasmonate (JA). We edited the barley ALLENE OXIDASE CYCLASE (HvAOC) gene encoding a JA biosynthetic enzyme. We examined hvaoc mutants for developmental phenotypes, genetic interactions and effects on the transcriptome. Defective HvAOC alleles reduced JA levels, and caused enhanced vegetative growth, faster flowering and lengthened grain, all phenotypes rescued by MeJA treatment. HvAOC control of grain length appears parentally-derived, consistent with enriched HvAOC expression in maternal compared to filial tissues. Grain dimension changes were uncoupled from hull size and correlated with larger endosperm cavities, more persistent maternal tissues and higher expression of genes linked to sucrose transport. This work provides the first genetic dissection of JA in barley and highlights roles in coordinating maternal tissues within grain.
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Journal articleMoffett ER, Gayford JH, Chen L, et al., 2026,
Biodiversity safeguards ecosystem services and functions worldwide.
, Nat Ecol EvolBiodiversity loss threatens ecosystem services on which humanity depends, yet the strength, form and context-dependency of biodiversity-ecosystem service and biodiversity-ecosystem function relationships remain poorly quantified. Here we synthesize 423 studies to determine how biodiversity affects ecosystem functioning and service delivery. We show that regulating services, including water quality and pollination, often exhibit linear relationships, suggesting an additive role for diversity. While biodiversity enhances most functions and services, our effect-size analysis shows that oceanic 'blue carbon' sequestration is exceptionally sensitive, revealing how critical marine biodiversity is for climate mitigation. Conversely, services such as hazard regulation appear relatively insensitive to biodiversity, instead depending on a few functionally unique foundational species whose persistence nonetheless is interdependent on the wider community. Our new synthesis enables the forecasting of impacts, for example, that biodiversity loss will reduce pest regulation in countries experiencing population growth and intensive development, and it also highlights how ecosystem services might be used to anticipate future problems.
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Journal articleWiddicombe B, Barritt JD, Pipatpadungsin N, et al., 2026,
Cryo-EM Analysis of Adenovirus Vector Reveals Purification Conditions Leading to Loss of Viral Fiber Proteins and Reduced Infectivity.
, Biotechnol BioengVaccines and gene therapies require efficient delivery of genetic material to host cells. Viral vectors leverage viruses' ability to enter host cells to achieve this. Following the SARS-CoV-2 vaccine and novel gene therapies that utilize adenovirus vectors, there has been an increase in the demand for large-scale production of vectors. A benefit of adenovirus vectors is that they can act as a "plug and play" tool for any future emerging diseases for the development of vaccines. A key obstacle was the heterogeneity that is found in the final product. This can reduce the functionality of the vector and affect immune responses. A possible origin of heterogeneity is the downstream processing, specifically the bind and elute steps of anion exchange chromatography (AEX), which is widely used at scale. To better understand the heterogeneity that AEX could elicit on the adenovirus capsid, cryogenic-electron tomography was used to assess the capsid integrity after a variety of chromatography conditions in comparison to a cesium chloride (CsCl) gradient ultracentrifugation purified control. To investigate the effect of absorption time during chromatography, AEX conditions with a 5, 10, and 20 min on-resin absorption periods were evaluated. Following AEX binding at pH 6.5, samples showed a reduction from 17% in the CsCl purified control to 10% infectious particles. When examined using electron microscopy, the virions exhibited aggregation and a decrease from 70% to 54% in fiber occupancy. After a 20 min AEX hold at pH 6.5 there was almost complete loss of infectivity and fiber occupancy decreased from ~70% to below 30%. Samples run at pH 8 did not show the same loss in infectivity when held bound for 20 min. This suggests that purification conditions can cause removal of the fiber protein, which was likely causing the decrease in infectivity, due to the fiber's role in cell entry. We hypothesize that fiber removal was caused by a combination of h
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Journal articleLiu Y, Fernandes N, Faulkner V, et al., 2026,
The lysine acetyltransferase Rv0998 coordinates transcriptional and metabolic adaptation of Mycobacterium tuberculosis to acidic pH
, Journal of Bacteriology, ISSN: 0021-9193Mycobacterium tuberculosis (Mtb) survives host defences by adapting to host conditions, including acid stress, during infection. A critical survival strategy involves pH homeostasis, mediated by complex signalling systems that regulate metabolic reprogramming and stress responses. While the lysine acetyltransferase Rv0998 is known to support Mtb hypoxia adaptation and metabolic flexibility, its role in acid stress remains unexplored. Here, we investigated the consequences of rv0998 deletion in 7H9 with glucose as the major carbon source. RNA-seq analysis showed that loss of Rv0998 altered the transcriptional response to acidic pH, including changes in the DosR regulon and pfkB/Rv2029c. Stable isotope tracing with [U-13C6]-glucose also showed reduced fractional 13C labelling across central carbon metabolites in the rv0998 mutant, with the largest decrease at acidic pH observed in upper glycolytic and connected hexose-phosphate intermediates. Growth and glucose-labelling phenotypes of dosR and pfkB mutants provided focused examples of stress-responsive and carbon-metabolic processes associated with the broader Rv0998 response. These findings indicate that Rv0998 contributes to coordinated transcriptional and metabolic adaptation of Mtb to acidic pH and support further investigation of how stress-responsive regulatory programmes are coupled to carbon metabolism during acid adaptation.
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Journal articleGan W, Garen J, Michaletz S, et al., 2026,
Thermal acclimation as an emergent property ofeconomically optimal photosynthesis
, New Phytologist, ISSN: 0028-646XLeaf-level photosynthesis acclimates to growth conditions over days to weeks, resulting in the instantaneous optimal temperature for photosynthesis (Topt) increasing with growth temperature (Tgrowth). This widely observed behaviour is reproduced as an emergent property of the P model, a generic model of primary production based on eco-evolutionary optimality hypotheses. We show, through comparisons with an experimental data set on the photosynthetic characteristics of three herbaceous plant species grown at different temperatures, that the P model yields a realistic linear increase in Topt with Tgrowth and a realistic peaked relationship between the photosynthetic rate at Topt (Aopt) and Tgrowth. These responses emerge primarily from thermal acclimation of a stomatal sensitivity parameter ;@= that determines the ratio of internal to ambient CO2 (ci:ca) and its sensitivity to vapour pressure deficit, without requiring any change in enzyme kinetics. Furthermore, the decline in Aopt at high growth temperatures, often attributed to heat stress, can be explained by the narrowing gap between Topt and Tgrowth as Tgrowth increases, a direct consequence of the @> ) Topt shift having a slope < 1. The P model as implemented here provides a mechanistic explanation for observed trends in Topt and Aopt with growth temperature, and additionally provides a scalable approach for improving representation of biochemical and stomatal acclimation in land surface models.Keywords: Eco-evolutionary optimality; P model; temperature acclimation; photosynthetic parameters; electron transport; carboxylation; vapour pressure deficit
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Journal articlePerren L, Livernois W, Woloszyn K, et al., 2026,
Topology-enforced synthesis of atomically precise silver nanoclusters in 3D DNA lattices.
, Sci Adv, Vol: 12DNA nanotechnology leverages the molecular design resolution of the DNA double helix to fold and tile matter into designer architectures. Recent advances in bioinorganic chemistry have exploited DNA/Ag+ affinity to carry out the templated reduction of silver nanoclusters. Here, we develop a unified method that leverages the topology of DNA triangles with embedded silver base pairs to nucleate controlled cluster growth in a mesoporous 3D lattice. Use of confocal fluorescence microscopy allows for the direct observation of reaction kinetics and reconstruction of the optical bandgap. These crystals yield molecular structures of Ag4 and Ag6 by x-ray diffraction in varying pyrimidine:pyrimidine pairs. Intercluster distances of less than 2 nanometers show observable electronic coupling, with red shifting observed relative to literature standards. A thorough computational investigation establishes a theoretical basis for our observed behavior and establishes the interplay between cluster size, charge, geometry, and resonance. We anticipate that these results will yield advances in materials synthesis, DNA-based plasmonic crystals, and optically active nanoelectronics.
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Journal articleCavan EL, Martin AH, Reid DG, et al., 2026,
A biological carbon pump code of practice for high seas fisheries
, Nature Reviews Earth and Environment, Vol: 7, Pages: 649-650Fishing has long been a concern to ocean ecosystems, but it can also impact the carbon cycle by disturbing the biological carbon pump (BCP). This Comment discusses whether a ‘BCP fisheries code of practice’ could and should be developed to incentivize natural resource management mechanisms that protect the BCP.
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