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Journal articleMaia RA, Oki Y, Medina I, et al., 2026, , 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.
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Journal articleHui T-Y, Epopa PS, Millogo AA, et al., 2026, , 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
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Journal articleDe Lorm TA, Heon SP, Bernard H, et al., 2026, , 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.
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Journal articleDi Domenico F, Kucharczyk MW, Patel R, et al., 2026, , 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
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Journal articleOh J, Jim茅nez JI, Kim J, 2026, , 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.
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Journal articleBose A, Bopanna Y, Shetty P, et al., 2026, , 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.
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Journal articleMajumdar A, Bagchi D, Kotta-Loizou I, et al., 2026, , J Hazard Mater, Vol: 513
Antimicrobial resistance (AMR) and antibiotic resistance (ABR) represent one of the most pressing global health threats, driven by the complex interplay between human, animal, and environmental factors. The One Health resistome framework recognises that resistance genes circulate continuously across clinical, agricultural, and environmental compartments through horizontal gene transfer, co-selection mechanisms, and anthropogenic contamination. This comprehensive review synthesises current evidence on integrated AMR surveillance, examining how digital technologies are transforming our capacity to monitor, predict, and respond to resistance emergence. Key advances include whole-genome sequencing enabling high-resolution pathogen tracking, metagenomics revealing environmental resistome diversity, machine learning algorithms predicting resistance phenotypes with >鈥85% accuracy, and point-of-care diagnostics extending sophisticated testing to resource-limited settings. Geographic information systems facilitate spatial hotspot identification, while wastewater-based surveillance provides early warning capabilities, detecting resistance genes before clinical manifestation. Despite technological progress, substantial challenges persist: fragmented data streams across sectors, lack of standardised environmental monitoring methods, limited laboratory capacity in low- and middle-income countries, and chronic underfunding. Emerging technologies, portable nanopore sequencing, CRISPR-based diagnostics, artificial intelligence, and blockchain-enabled data governance promise to address these gaps. Realising comprehensive One Health resistome surveillance requires sustained investment in interoperable digital infrastructure, international standardisation, capacity building, and political commitment to cross-sectoral coordination, prioritising equitable global implementation.
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Journal articleLau R, Giblin S, Sugar A, et 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: 0027-8424Streptococcus 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鈥慳ttracting chemokines such as CXCL8. Here, we integrate cryo鈥慹lectron microscopy (cryo鈥慐M), 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鈥憁ediated 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鈥慹nriched 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鈥憊irulence therapies and vaccine strategies targeting SpyCEP.
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Journal articleEndres R, 2026,
The unreasonable likelihood of being: Origin of life, terraforming, and AI
, npj Systems Biology and Applications, ISSN: 2056-7189 -
Journal articleEneli AA, Siu PC, Perez MF, et al., 2026, , G3 (Bethesda), Vol: 16
Malaria in sub-Saharan Africa is transmitted by mosquitoes from the Anopheles genus. Efforts to control the spread of malaria have often focused on these vectors, but little is known about the demographic history of populations and species of Anopheles mosquitoes. Here, we adapt and apply an innovative generative deep learning algorithm to infer the joint evolutionary history of Anopheles gambiae populations sampled in Guinea and Burkina Faso. We further develop a model selection approach and discover that an evolutionary model with migration fits this pair of populations better than a model without post-split migration. For the migration model, we find that our method accurately captures population genetic differentiation. These findings demonstrate that machine learning and generative models are a valuable direction for future understanding of the evolution of malaria vectors, including the joint inference of demography and natural selection. Understanding changes in population size, migration patterns, and adaptation in hosts, vectors, and pathogens will assist malaria control interventions, with the ultimate goal of predicting nuanced outcomes from insecticide resistance to population collapse.
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Journal articleStegemann A, Liu S, Retana Romero OA, et al., 2026, , Nat Neurosci
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Journal articleGao C, Meng X, Chen X, et al., 2026, , Science, Vol: 393, Pages: 65-70
Plants activate pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) to combat pathogens. However, how these systems coordinate immune activation while preventing autoimmunity remains poorly understood. In this study, we uncovered a regulatory mechanism in which surface immune signaling unlocks nucleotide-binding leucine-rich repeat (NLR) immune receptor activation through mRNA splicing. We identified an N-terminal prodomain in the potato late blight resistance protein Rpi-vnt1.1 that inhibits resistosome formation, preventing potential autoactivation of this NLR. Upon pathogen perception, PTI signaling induced alternative splicing of Rpi-vnt1.1 mRNA, removing this inhibitory element. This primed Rpi-vnt1.1 for activation by the Phytophthora infestans effector AVRvnt1, enabling resistosome assembly and immune signaling. The widespread conservation of N-terminal extensions in coiled coil-type NLRs points to a common regulatory mechanism in preventing potential autoactivation while preserving pathogen sensitivity.
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Journal articleBanks AM, Abdulmutalib U, Wain B, et al., 2026, , Trends in Biotechnology, ISSN: 0167-7799
Poly(ethylene terephthalate) (PET) is one of the most widely used plastics in food and textile applications, yet post-consumer PET waste persists and accumulates in the environment as macro- and microplastics with adverse health and ecological impacts. Although PET-hydrolysing enzymes have been extensively studied in vitro, whole-cell microbial systems capable of using PET as a growth substrate remain limited, particularly for difficult-to-collect waste. Here, we engineer an environmental bacterium to directly assimilate PET. A strain of Pseudomonas umsongensis capable of metabolising the PET monomer terephthalic acid was isolated and engineered to secrete the high-activity PET hydrolase polyester hydrolase Leipzig 7 via a recombinant twin-arginine translocation motif signal peptide. PET bioavailability was further enhanced through solvent-based pretreatment to generate an amorphous, macroporous substrate. The engineered strain demonstrated direct PET utilisation and hydrolysis, supporting self-sustaining microbial growth. Additionally, in non-sterile wastewater the strain survived and hydrolysed PET microplastics, highlighting its potential for bioremediation and sustainable upcycling applications.
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Journal articleMajumdar A, Kotta-Loizou I, Buck M, et al., 2026, , J Hazard Mater, Vol: 512
Climate change-induced warming and arsenic soil contamination synergistically threaten agricultural sustainability by restructuring microbial communities and accelerating antimicrobial resistance dissemination. Here, through integrated greenhouse and field trials, we demonstrate that Bacillus subtilis 168-derived biofilm and sublancin, a glycosylated antimicrobial peptide, simultaneously immobilise rhizospheric arsenic and suppress horizontal transfer of antibiotic resistance genes (ARGs). Temperature-dependent biofilm formation (25-35°C) enhanced arsenic sequestration within the extracellular polymeric substance matrix, with SEM-EDX revealing a 74% increase in arsenic weight percentage at 35°C and ToF-SIMS confirming ∼14-fold and ∼9-fold increases in root-associated arsenic on biofilm-colonised surfaces in greenhouse and field trials, respectively. Sublancin production peaked at 30°C (129.72鈥痬g鈥疞鈦¹), selectively suppressing all 12 tested pathogenic Gram-positive species by 74-86% while preserving Gram-negative communities. Bio-amendment reduced horizontal gene transfer frequency by 74.7% (p鈥<鈥0.001) across all temperature regimes. Transcriptomic profiling revealed coordinated upregulation of exopolysaccharide biosynthesis (FDR ∼1.0鈥× 10鈦²鈦) and sublancin machinery (sunA: +3.5鈥痩og鈧), alongside downregulation of conventional ARGs (vanA, blaTEM: -2.5 to -4.0鈥痩og鈧). These findings establish sublancin as a dual-function, climate-adaptive soil bio-amendment simultaneously addressing arsenic bioaccumulation and antibiotic resistance gene dissemination under warming scenarios.
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Journal articleGottweis J, Weng W-H, Daryin A, et al., 2026, , Nature, ISSN: 0028-0836
Scientific discovery is driven by scientists generating hypotheses for complex problems that undergo rigorous experimental validation. To augment this process, we introduce Co-Scientist, a multi-agent artificial intelligence (AI) system built on Gemini for structured scientific thinking and hypothesis generation. Co-Scientist aims to help scientists discover new original knowledge. Conditioned on their research objectives and previous scientific evidence, it formulates demonstrably novel research hypotheses for experimental verification. The system’s design involves agents continuously generating, critiquing and refining hypotheses accelerated by scaling test-time compute. Key contributions include (1) a multi-agent architecture with an asynchronous task execution framework for flexible compute scaling, and (2) a tournament evolution process for self-improving hypotheses generation. Automated evaluations show continued benefits of test-time compute scaling, improving hypothesis quality over time. Although this is a general-purpose system, we focus the validation in three biomedical applications: drug repurposing; novel-target discovery1; and explaining mechanisms of antimicrobial resistance2. Specifically, Co-Scientist helped to identify new drug-repurposing candidates and synergistic combination therapies for acute myeloid leukaemia that were validated through in vitro experiments. These real-world validations demonstrate the potential of Co-Scientist to accelerate scientific discovery and usher in an era of AI-empowered scientists.
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Journal articleNozawa LCC, BanksLeite C, Lima MR, et al., 2026, , Journal of Biogeography, Vol: 53, ISSN: 0305-0270
<jats:title>ABSTRACT</jats:title> <jats:sec> <jats:title>Aim</jats:title> <jats:p>We investigated how bird functional diversity varies across forest habitat types with distinct successional trajectories, namely (1) natural succession forests, with naturally regenerating forests established on former grasslands; (2) secondary forest remnants resulting from deforestation; and (3) conserved forests.</jats:p> </jats:sec> <jats:sec> <jats:title>Location</jats:title> <jats:p>Araucaria forests in southern Brazil.</jats:p> </jats:sec> <jats:sec> <jats:title>Time Period</jats:title> <jats:p>1991 to 2015.</jats:p> </jats:sec> <jats:sec> <jats:title>Taxon</jats:title> <jats:p>Birds.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We compiled functional trait data for bird communities from 47 sites of Araucaria forests under three distinct successional trajectories. We calculated standardised effect sizes for functional richness (SESFRic) and functional dispersion (SESFDis), and generalised linear models were initially fitted. To account for spatial autocorrelation, we fitted spatial models (spaMM) to assess whether forest habitat type, forest cover, and patch size help explain functional variation in bird assemblages. In addition, we performed canonical correspondence analysis to evaluate differences in trait composition among forest habitat types.</jats:p> </jats:sec> <jats:sec>
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Journal articleGider Yaman G, Bozkurt O, Akgun E, et al., 2026, , Indian J Pediatr, Vol: 93
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Journal articleDas A, Majumdar A, Thakur BK, et al., 2026, , Water, Air, & Soil Pollution, Vol: 237, ISSN: 0049-6979
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Journal articleBrook T, Piponi K, Collins T, et al., 2026,
Genomic architecture and breeding trade-offs of coconut drought tolerance
, Plants, People, Planet, ISSN: 2572-2611Climate change threatens coconut palms (Cocos nucifera), a vital tropical crop supporting millions, with yields projected to drop nearly 50%. We assessed drought tolerance in over four thousand trees from the world’s largest coconut collection in Côte d'Ivoire, using 30 years of yield and climate data. Our reaction norm modelling approach revealed substantial variation in drought tolerance and a potential trade-off with yield. Using a quantitative genomic approach, we identified a substantial heritable component, highlighting the potential for genomic selection approaches in breeding climate-resilient coconuts.
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Journal articleSanchez-Garrido J, David S, Rattle J, et al., 2026, , J Infect Dis
BACKGROUND: Klebsiella pneumoniae (KP) is a critical-priority organism due to prevalent last-line antibiotic resistance. Alternative treatments, including vaccines and monoclonal antibodies (mAb), depend on antigen (Ag) expression at infection sites for immunotherapeutic activity. However, the relationship between genome-encoded Ag presence and Ag expression is often overlooked. Here, we use the KP type 3 fimbrial (T3F) subunit MrkA as a prototype to build a generalisable framework to assess Ag expression and its correlation with in vivo immunotherapeutic efficacy. METHODS: We perform genomic analysis of 1649 KP genomes for T3F genes, including structural and regulatory components. We generate isogenic mutants with absent, normal or overexpressed MrkA and profile MrkA expression at single-cell level from murine pneumonia and bacteraemia models. We compare anti-MrkA mAb efficacy in vivo against strains with normal and enhanced MrkA expression. RESULTS: T3F structural and regulatory genes are highly conserved, however, regulatory gene disruption (mrkH) is more common than structural gene disruption and, in both cases, MrkA Ag is not expressed. In vivo Ag profiling revealed site-specific differences in MrkA expression, with ∼20% of KP cells expressing MrkA in the lung versus ∼5% in the bloodstream. Anti-MrkA mAb activity was dependent on MrkA abundance, with significantly enhanced efficacy following infection with MrkA-overexpressing KP. CONCLUSIONS: Regulatory genes are as important to characterise as structural gene presence when evaluating antigen candidates in clinical isolates, and Ag expression can vary by anatomical context. For MrkA, Ag abundance determines anti-MrkA mAb activity, suggesting infections with high MrkA expression will respond better to therapy.
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Journal articleEttema TW, Inaba-Inoue S, Thangaratnarajah C, et al., 2026,
Shared structural mechanisms of alternating access between the secondary peptide transporter SbmA and ABC transporters
, Nature Communications, Vol: 17, ISSN: 2041-1723SbmA is a membrane transporter from Escherichia coli that imports antimicrobial peptides. SbmA belongs to the SbmA-like peptide transporter (SLiPT) family. Although the protein is a secondary active transporter that is energized by the proton gradient, it is structurally related to the transmembrane domain (TMD) of ATP-binding cassette (ABC) transporters. SbmA therefore bridges the structural divide between primary and 61 secondary transporters. However, it remains unclear, if SbmA also shares the mechanism of alternating access with ABC transporters, because only a single (outward-open) state is resolved. Here, we show by sequence analysis that SbmA is likely evolved from the TMD of an early ancestor of the ABC transporter YddA. We determine the cryogenic electron microscopy structures of SbmA in occluded and inward-facing states. These conformations closely resemble equivalent states found in ABC trans- porters, indicating a shared structural mechanism of transport. In contrast to ABC transporters, where nucleotide binding, hydrolysis and release steer conformational changes necessary for substrate translocation, electron paramagnetic resonance (EPR) spectroscopy and molecular dynamics (MD) simulations reveal how pH changes induce conformational transitions in SbmA, consistent with a mechanism of substrate internalization that utilizes the transmembrane proton gradient.
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Journal articleHobbs B, Limmer N, Clenshaw GL, et al., 2026, , Phys Chem Chem Phys
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.
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Journal articleLarrouy-Maumus G, 2026,
Metabolomics profiling reveals changes in peptidoglycan and redox metabolism between ancient and modern Mycobacterium tuberculosis
, Microbiology Spectrum, ISSN: 2165-0497Mycobacterium tuberculosis (Mtb), the cause of tuberculosis, kills over one million people worldwide each year. Mtb is classified into ten distinct lineages, each harboring unique genetic changes that influence its survival, virulence, and transmissibility. Although metabolism plays a critical role in Mtb infection and persistence, the metabolomic profiles of different Mtb lineages remain poorly characterized. Here, by using metabolomic and bioinformatic approaches, we have determined the metabolome of representative strains belonging to three main lineages, namely lineage 1, lineage 2 and lineage 4. We show that the ancient lineage 1 has considerable differences in its metabolome compared to lineages 2 and 4. Those differences are mainly related to amino acids, peptidoglycan synthesis intermediates and ergothioneine, a sulphur-containing histidine derivative with potent antioxidant and redox properties. Taken together, these data represent the first comprehensive analysis of the metabolome of three main Mtb lineages.
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Journal articleOvwemuvwose J, Prentice IC, Graven HD, 2026,
Uncertainty in land carbon fluxes simulated by CMIP6 models from treatments of crop distributions and photosynthetic pathways
, Biogeosciences, ISSN: 1726-4170A reliable representation of the diversity of vegetation in terrestrial ecosystems is needed for the accurate simulation of present and future biogeochemical cycling and global climate, particularly as climate change affects different vegetation types differently. We compare the distributions of crops and of C3 versus C4 photosynthetic pathways in both natural vegetation and crops across Earth System Models in the 6th Coupled Model Intercomparison Project (CMIP6). We find a large range in C3 and C4 crops, natural and total vegetation for area and gross primary production (GPP) across the models. Even though 10 of the11 models used Land Use Harmonisation (LUH2) crop areas as input data, modelled total crop area ranges from -28 to +10 % of a satellite-based estimate. The C3 and C4 crop areas were -56 to +15 % and -100 to +38 % of LUH2 for 2014, respectively. The C4 fraction of total vegetation area in the models is 9-25 %, compared to 20 ± 3 % in observation-based estimates for the year 2014. Total global GPP varies by a factor of two across the models, and the C4 fraction of GPP ranges from 12 to 27 %. Simulated trends in the fraction of GPP by C3 versus C4 vegetation type (-20 to +29 %) would have changed global stable carbon isotopic discrimination by -0.35 to +0.11 ‰ over 1975-2005, not including changes in discrimination over time within C3 and C4 vegetation, indicating that modeled changes in the fraction of GPP by C3 and C4 vegetation do not account for the +0.7 ‰ increase indicated by atmospheric data. Disparity in vegetation with these photosynthetic pathways in models contributes to uncertainty in land carbon flux simulations, and further constraints and improvements in models are needed.
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Journal articleZhao Z, Vercellino I, Whitelegge JP, et al., 2026, , Nature Communications, ISSN: 2041-1723
Robust oxygenic photosynthesis requires the efficient assembly and repair of the multi-subunit oxygen-evolving photosystem II (PSII) complex. Previous cryogenic electron microscopy (cryo-EM) structures of PSII assembly/disassembly intermediates have relied on the analysis of deletion mutants or removal of PSII subunits in vitro. Here we determine the cryo-EM structures of naturally occurring dimeric PSII intermediates from the cyanobacterium Thermosynechococcus vestitus at a resolution of about 2.2 Å. These intermediates contain inactive dimers lacking the oxygen-evolving complex (OEC) and semi-active dimers with the OEC present in one of the two monomers. Our structural data provide a mechanism for how assembly and disassembly of the Mn4CaO5 cluster is coordinated with the binding and release of the extrinsic proteins: restructuring of the C-terminal tail of D1 subunit during assembly or disassembly of the Mn cluster triggers conformational changes in D2, CP47 and CP43 to drive the binding/release of the extrinsic proteins. A combination of structural and mass spectrometry data also suggests that the inactive PSII complexes may include damaged complexes containing oxidized D1-His332, a monodentate ligand to one of the Mn ions of the OEC.
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Journal articleUrban MC, Zurell D, Bocedi G, et al., 2026, , Nat Ecol Evol
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Journal articleGroff A, Lu Y, Feeney M, et al., 2026,
Sustainable production of myoglobin meat protein in plant chloroplasts
, Frontiers in Plant Science, ISSN: 1664-462XAlternative routes for producing animal proteins are crucial for reducing the reliance on traditional livestock farming, which contributes significantly to greenhouse gas emissions, deforestation, and water consumption. Myoglobin (Mb) is an important oxygen-binding hemoprotein found in vertebrate muscle, that enhances the nutritional and sensorial properties of meat. Due to its unique functionality, Mb has been heterologously expressed in a variety of organisms, although only transient expression in Nicotiana benthamiana has been reported for higher plants. In this study, we used chloroplast transformation technology to express porcine Mb in higher plants (tobacco, a non-edible model plant, and lettuce, an edible host) and bovine Mb in the green alga Chlamydomonas reinhardtii. Mb accumulation was estimated by immunoblotting and found to be much higher in tobacco (2.7% total soluble protein (TSP)) and lettuce (1.5% TSP) than Chlamydomonas reinhardtii (<0.25% TSP). The expression in tobacco chloroplasts is also superior to tobacco nuclear expression (using either the cauliflower mosaic virus 35S promoter or Arabidopsis thaliana ubiquitin promoter). Total heme levels were elevated in myoglobin-producing mutants compared to control plants, although porcine Mb purified from tobacco leaves exhibited approximately 35% heme-binding (compared to 80% heme-binding in E. coli-expressed Mb), despite being correctly folded, suggesting that heme availability might be a bottleneck. Overall, our work describes the first report of stable Mb production in higher plants and its effect on photosynthesis and heme levels. This provides a foundation for future plant-made animal proteins for food applications.
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Journal articleNollet M, Ba W, Anuncibay Soto B, et al., 2026,
Modeling the prodromal phase of Alzheimer’s disease: selective amyloid-driven failure of cholinergic medial septal neurons perturbs REM sleep, cognition, emotion, and broadcasts pathology in aging mice
, eLife, ISSN: 2050-084XIn humans, decreases in rapid eye movement sleep (REMS) strongly predict Alzheimer's disease (AD), alongside early degeneration of basal forebrain cholinergic neurons. We examined how β- amyloid pathology gradually erodes mouse cholinergic neurons. The familial AppNL-G-F allele was selectively expressed in medial septal (MS) cholinergic neurons of both sexes and compared with mice with global AppNL-G-F expression and selective genetic lesions of MS cholinergic cells. By 14 months, targeted AppNL-G-F allele expression had caused loss of 25% of MS cholinergic neurons and produced amyloid deposition in their terminal fields, particularly the hippocampus. REMS was reduced, together with cognitive and emotional alterations mirroring phenotypes in global mutants, which also showed selective MS cholinergic cell loss. Genetic lesioning of MS cholinergic cells recapitulated most phenotypes, identifying cholinergic loss, not amyloid deposition, as a probable cause of these phenotypes. Nevertheless, broadcasted amyloid from MS cholinergic neurons likely induced hippocampal astrocyte activation and epileptiform spikes.
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Journal articleFrankel G, 2026, , Nature Communications, ISSN: 2041-1723
Bacterial conjugation, the process of horizontal gene transfer between bacteria, is initiated by mating pair formation (MPF) via a conjugative pilus. Conjugation of the IncP RP4 plasmid is mediated by short mating pili. Here, we report the cryo-EM structure of the RP4 pilus at 2.74 Å resolution. Uniquely, both the structural and quantitative mass spectral analyses revealed that the cyclic TrbC pilin subunit is not lipidated. Consistently, an E. coli pgsA mutant lacking phosphatidylglycerol (PG) can serve as a donor of RP4 but not of F- (pKpQIL), H- (R27) or W- (R388) pili, whose biogenesis and DNA transfer is PG-dependent. RP4 is the first example of a lipid-independent functional mating pilus. This discovery suggests that an amphipathic lipid moiety is not universally essential for the biogenesis of conjugative pili and MPF, providing an alternative model for their assembly and function. These data expand our understanding of the diverse bacterial mechanisms employ to transfer genetic material.
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Journal articleTarantola L, Tyler EJ, Liu Y, et al., 2026, , Nat Commun, Vol: 17
The tumor extracellular matrix (ECM) is increasingly recognized as a key driver of immune suppression and therapy resistance in cancer. However, the specific ECM components and mechanisms that create this immunosuppressive environment remain poorly understood, hindering the development of new therapies. Here, we use comprehensive multi omics profiling of triple-negative breast cancer (TNBC), an aggressive and treatment-resistant subtype, to investigate this issue. We report that ECM immunomodulation in TNBC is mediated by post-translational glycan modifications on ECM proteins. Using decellularized human TNBC samples, we show that targeted enzymatic removal of these ECM glycans modifies the tumor immune microenvironment. This modification reprograms tumor-associated myeloid cells toward an immunomodulatory phenotype and improves infiltration of T cells. Notably, ECM desialylation alters selectin and selectin-ligand programs on T cells, consistent with improved trafficking and intratumoral access. In parallel, macrophage-T cell interactions are reshaped, leading to reduced T cell exhaustion. Our findings identify ECM glycan modifications as critical regulators of the innate and adaptive TNBC immune microenvironment. They suggest that targeting ECM glycosylation could offer potential strategies to boost anti-tumor immunity in this aggressive breast cancer subtype.
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