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Journal articleCasadio R, Lu ZJ, Mathews DH, et al., 2026,
Computational Resources for Molecular Biology 2026.
, J Mol Biol, Vol: 438 -
Journal articleZhao H, Pye R, Walker G, et 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: 0022-2836Only 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.
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Journal articleLlewellyn T, Vogler A, 2026,
A robust phylogenetic framework for ophiostomatoid fungi: orders Ophiostomatales and Microascales (Sordariomycetes, Ascomycota)
, MycoKeys, Vol: 140, Pages: 103-129, ISSN: 1314-4057Ophiostomatoids are an ecological group of microfungi that commonly associate with bark and ambrosia beetles. In addition to being insect symbionts, they play significant ecological roles as plant pathogens and include species responsible for major forest tree diseases. Despite their ecological similarities, ophiostomatoid fungi are distributed across two distantly related orders, Microascales and Ophiostomatales, which include many additional fungi with diverse ecological lifestyles. Previous studies have typically focused on localised taxonomic issues or specific fungal ecologies. As a result, public repositories suffer from fragmented locus coverage, sequence misidentifications, and uneven taxon sampling, leaving the community without a standardised, comprehensive dataset to study these fungi at scale. To address this, all available ophiostomatoid fungal sequence data across seven widely used marker loci were curated and analysed to reconstruct densely sampled alignments and trees covering 918 concatenated Microascales sequences and 859 Ophiostomatales sequences. Evaluation of locus performance showed that whilst individual loci exhibit extreme state frequency heterogeneity, composition bias, and topological discordance, concatenated datasets produce robust, well-supported topologies consistent with published genomic studies. Integrating phylogenies with broad ecological trait data reveals a clear contrast in data distribution between the two orders, with ecological lifestyles and beetle associations being broadly uniform and stable across the Ophiostomatales tree but highly heterogeneous in the Microascales, despite comparable species richness. These macroecological data distributions are also shaped by taxonomic philosophies, whereby the fragmentation of Microascales into small, restricted genera tends to visually amplify trait variation, whereas the large, heterogeneous genera of Ophiostomatales can obscure it. This unified, fully reproducible framework establ
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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 SystGene 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 articleJordan S, Biswas P, Alberdi ML, et al., 2026,
Design of a live-attenuated bacterial vaccine using effector network engineering
, Nature Communications, Vol: 17, ISSN: 2041-1723Enteropathogenic Escherichia coli (EPEC) and Citrobacter rodentium (CR) are extracellular enteric attaching and effacing (A/E) pathogens of humans and mice, respectively. Their virulence relies on intimate bacterial attachment and a network of type III secretion system effectors. Here, through systematic reduction and redesign of the effector network in CR, we develop an attenuated strain, CRV (CR Vaccine), encoding a subset of ten effectors. CRV colonises C57BL/6 mice ~100-fold lower than wild type CR (CRWT) without causing overt pathogenesis. Moreover, C3H/HeN mice, which succumb to CRWT infection, survive CRV challenge. Vaccination with CRV confers protection against subsequent CRWT infection in both mouse strains. Serological analysis reveals a repertoire of dominant CR antigens, including the O-antigen, the virulence factors intimin, EspA and Tir and the outer membrane proteins Lpp, OmpA, MetQ and CARC (an AIDA-like autotransporter). We show that CRWT and CRV immunisation elicits comparable B cell and antibody responses, which is contingent on intimate bacterial attachment. A corresponding EPEC strain (E. coli Vaccine, ECV) effectively colonises epithelial cells in a gut-on-chip model. These findings establish effector network minimisation as a generalisable strategy for rational bacterial attenuation and live-attenuated vaccine design.
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Journal articleGeorgiou C, Liu Q, Bruno F, et al., 2026,
Rare Hematopoietic Stem Cells resilient to infection-induced stress sense yet withstand inflammation.
, BloodHematopoietic stem cells (HSCs) sustain lifelong hematopoiesis as their progeny differentiate into all blood cell lineages. Homeostatic HSCs are mostly quiescent and only rarely divide, however their proliferation and differentiation rates can be modulated by external factors. Acute and chronic infections from a wide range of pathogens are known to challenge HSCs at the population level, being forced to respond to inflammation-mediated organismal demand to replenish the myeloid cell pool. However, less is known about the degree of heterogeneity in the HSCs' response to inflammation at the single cell level. Here, using a natural murine malaria model and an NHS-ester biotin dilution assay we identify two subsets of HSCs, BiotinLo and BiotinHi, with distinct proliferation kinetics. Using combined functional, single-cell transcriptomics and phenotypic analyses, we uncover that BiotinHi HSCs remain highly functional despite expressing strong interferon response signatures. These resilient HSCs are more poised to enter cell cycle than control HSCs, but do not divide. They maintain less active mitochondria and express higher levels of CD74 and MHC-II. Additionally, they express higher levels of integrin β2/CD18, which suggest they may have specific interactions with the bone marrow microenvironment. Similar patterns of NHS-ester biotin dilution were elicited by LPS and poly (I:C) challenges. These findings highlight previously unmeasured heterogeneity in the response of HSCs to acute infection-induced inflammation and demonstrate that a likely reserve pool of HSCs remains highly functional during Plasmodium infection not because cells are shielded, but because they maintain a stemness associated metabolic profile despite effectively sensing inflammation.
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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, 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 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 articleZaffaroni-Caorsi V, Nou-Plana I, Secchi E, et al., 2026,
Experimental design for testing the impact of anthropogenic noise on marine deuterostome invertebrates in the laboratory
, Bioacoustics, Vol: 35, Pages: 591-616, ISSN: 0952-4622 -
Journal articleLiu Y, Ruecker N, Faulkner V, et al., 2026,
Rv3400 is a phosphoglucomutase required for trehalose metabolism in Mycobacterium tuberculosis
, Journal of Bacteriology, ISSN: 0021-9193Mycobacterium tuberculosis (Mtb) causes over 1 million deaths from tuberculosis (TB) every year and remains a major burden on human health. Reducing the deadly impact of TB requires a better understanding of the strategies used by M. tuberculosis to adapt its metabolism, survive, and persist in the human host. Previous enzymological studies reported that the Mtb rv3400 gene encodes a β-phosphoglucomutase; however, its role in M. tuberculosis metabolism had not been investigated. Here, we show that deletion of rv3400 causes a 30-fold increase in β-D-glucose-1-phosphate, confirming its primary function as a β-phosphoglucomutase. Deletion of rv3400 also causes a growth defect when trehalose is the sole carbon source. Targeted metabolomics revealed that metabolites associated with redox homeostasis, including ergothioneine, mycothiol, and mycothione, are decreased in the Mtb Δrv3400 strain compared with the wild type, indicating altered tolerance to redox stress. Consistent with this, the Δrv3400 strain showed increased susceptibility to oxidative stress induced by H2O2 and cumene hydroperoxide, conditions that Mtb encounters during infection. This work advances our understanding of trehalose metabolism in Mtb and suggests that Rv3400 may represent a target for the development of new antimicrobial therapies.
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Journal articleZhang X, Zhang X, Zhang F, et al., 2026,
Multi-frequency microwave remote sensing reveals stratified forest responses to diverse drought stresses
, International Journal of Applied Earth Observation and Geoinformation, Vol: 153, ISSN: 1569-8432Under climate change, increasing frequency and intensity of droughts pose severe threats to forest water dynamics and ecosystem stability. However, layer-specific responses to drought and their global spatial patterns remain insufficiently explored. This study utilized multi-frequency vegetation optical depth (VOD) datasets (X-, C-, and L-bands) that are sensitive to canopy, sub-canopy, and woody tissue moisture, to explore stratified forest responses at the global scale. A drought-induced relative anomaly index (ΔVOD%) was integrated with the standardized precipitation evapotranspiration index to characterize moisture dynamics under different drought types. Vertically, the canopy exhibited the strongest response intensity (mean ΔVOD% in the X-band = 44.5 % ± 20.9 %), whereas the woody tissue layer showed weaker but more delayed and persistent responses (mean lag = 2.56 and 2.44 months, respectively). A clear vertical gradient was identified: response intensity decreased from the canopy to the woody tissue layer, whereas lag and duration increased. Spatially, stronger canopy and sub-canopy responses were concentrated in evergreen broadleaf forests and tropical-temperate regions, while woody tissue responses were more pronounced in savannas and cold regions. Evergreen needleleaf, deciduous broadleaf, mixed forests, and arid zones exhibited clear inter-layer differences in response lag, whereas others showed relatively small variations. By leveraging the penetration capability of microwave remote sensing, we elucidated global patterns of layer-specific response intensity, lag, and duration and examines the effects of drought type, forest type, and climate zone on moisture dynamics. These findings provide new insights into global forest water responses under drought stress and improve remote sensing-based monitoring of forest drought impacts.
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Journal articleHodges PW, Arendt-Nielsen L, Bannister K, et al., 2026,
Central sensitization: when is this the right terminology?
, Pain, Vol: 167, Pages: 1986-1991 -
Journal articleYi L, Kulik N, Shao S, et al., 2026,
The transmembrane domain is a primary determinant of the location and substrate specificity in cyanobacterial FtsH heterocomplexes
, Algal Research, Vol: 98, ISSN: 2211-9264Membrane-embedded FtsH proteases play important and diverse physiological roles in prokaryotes, chloroplasts and mitochondria, but how substrates are distinguished remains unclear. The cyanobacterium Synechocystis sp. PCC 6803 contains four FtsH homologs organized into two distinct heterocomplexes and one homocomplex. The two heterocomplexes, derived from a recent gene duplication event, are the essential FtsH1/3 complex found in the cytoplasmic membrane, and the thylakoid-embedded FtsH2/3 complex, with a role in the repair of photodamaged photosystem II. Using a domain swapping approach, we demonstrate here that the transmembrane domains of FtsH1 and FtsH2 are primary determinants of the cellular location and functional differences between the FtsH1/3 and FtsH2/3 complexes, whereas the soluble AAA+ (ATPases associated with diverse cellular activities) and protease domains and the soluble linker were largely interchangeable under the conditions tested. Overall, our findings identify the transmembrane domain as an important determinant of both the location and substrate specificity of FtsH heterocomplexes and support a role for this domain in their functional evolution.
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Journal articleFerrando-Marco M, Lin S, Garcia Del Valle B, et al., 2026,
HDAC1/2-mediated repression of Wnt receptor expression orients asymmetric division polarity in Caenorhabditis elegans.
, Development, Vol: 153Asymmetric 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 Caenorhabditis 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 homologue) and cam-1 (Ror homologue) as key targets. Single-molecule fluorescence in situ hybridisation 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.
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Journal articleRowell J, Yanez DC, Ross S, et al., 2026,
The Thymic Microenvironment Shapes Age-Related Qualitative Changes in the TCR Repertoire.
, Aging Cell, Vol: 25Ageing impairs immune function, increasing susceptibility to infection, autoimmunity and inflammation. The thymus undergoes involution during childhood, and thymocyte and thymic epithelial cell (TEC) numbers decline. Given that adaptive immunity depends on T-cells recognising diverse antigens via their unique T-cell receptor (TCR), the precise age-related changes in TCR repertoire composition are key to understand immunity. To investigate the influence of age on the thymic TCR repertoire we sequenced TCRα and TCRβ transcripts from developmentally defined thymocyte populations from 4-week, 12-month and 18-month-old mice, and from thymocytes recovering from hydrocortisone-treatment, and athymic recipients of RAG1-deficient thymus transplants. The 18-month thymus selected TCR repertoires with distinctive patterns of VxJ and CDR3 k-mer usage compared to young thymus, indicating it had a qualitatively different repertoire with different specificity. It also selected a less diverse TCRβ repertoire with more expanded clones than young thymus. On recovery from hydrocortisone-treatment, both 4-week and 12-month thymus showed bias towards foetal-like 3'TRAVx5'TRAJ rearrangements, but 12-month thymus also produced less diverse and evenly distributed TCRβ repertoires, with increased expansion of TCRβ clones at the CD4-CD8-CD25+CD44-intracellularTCRβ+ stage, increased TRBJ-1-cluster usage and distinctive patterns of combinatorial VxJ usage. Transplantation of athymic nude recipients with old RAG1-deficient thymus generated less diverse, less evenly distributed TCR repertoires with different combinatorial VxJ usage than those generated by young transplants. Taken together our experiments show that the old thymus generates qualitatively different TCR repertoires than young thymus and the non-lymphoid compartment of the thymus contributes strongly to these changes and to age-associated decline in TCR repertoire diversity.
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Journal articleMishra V, Biswas P, Kozik Z, et al., 2026,
EspO-mediated neutrophil accumulation drives lethality during Citrobacter rodentium infection in interleukin-22-deficient mice.
, PLoS Pathog, Vol: 22Citrobacter rodentium (CR) is a murine-specific enteric pathogen widely used to model infections of the attaching and effacing pathogens enteropathogenic and enterohaemorrhagic Escherichia coli. Infection induces colonic epithelial damage and inflammation that are resolved in resistant mice but result in severe disease and mortality in mice lacking interleukin-22 (IL-22). While IL-22-deficient (Il22-/-) mice succumb to CR infection due to dehydration, in part mediated by disruption of the barrier integrity by the type III secretion system (T3SS) effector EspF, the contribution of immunopathology to infection outcomes is not known. Here, using CR we tested whether dysregulated neutrophil responses drive disease progression in Il22-/- mice. We show that IL-22 deficiency is associated with progressive colonic pathology and increased neutrophil accumulation and activity in the colonic mucosa. Infection of mice with CR lacking the T3SS effector EspO, which is implicated in neutrophil recruitment, resulted in markedly reduced neutrophil accumulation and activity in Il22-/- mice without altering bacterial burden. Notably, CRΔespO infection led to reduced colonic inflammation and complete survival of Il22-/- mice. Consistent with these findings, CXCR2 antagonist treated Il22-/- mice displayed attenuated disease severity and delayed mortality. Together, we identified EspO as the second effector, alongside EspF, whose deletion results in survival of CR-infected Il22-/- mice. Moreover, these findings suggest that excessive neutrophil accumulation and activity are key drivers of lethality during CR infection in Il22-/- mice and that EspO amplifies neutrophil-dependent pathology within a vulnerable epithelial environment.
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Journal articleGodson A, Eddie L, Schuster M, et al., 2026,
NbRD21 protease controls receptor kinase homeostasis in Nicotiana benthamiana.
, New Phytol, Vol: 251, Pages: 2741-2752RD21-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.
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OtherEwe CK, 2026,
Who chooses open peer review and is it an indicator of article quality? An observational study of PLOS journals
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Journal articleBi Y, Glymenaki M, Valdivia-Garcia MA, et al., 2026,
Trimethylamine N-oxide, a bariatric surgery-associated host-microbial co-metabolite, reduces colonic tumorigenesis in a sex-dependent manner
, Cellular and Molecular Gastroenterology and Hepatology, ISSN: 2352-345XBackground & AimsTrimethylamine N-oxide (TMAO) is a host-microbial co-metabolite that significantly increases following Roux-en-Y gastric bypass (RYGB). While TMAO is associated with cardiovascular diseases, its role in colorectal cancer (CRC) remains unclear.MethodsFabplCre;Apc15lox/+ mice, a genetically altered CRC model, together with murine macrophages and human colonic cancer cells (HCT-116) were used to investigate TMAO impact on colonic tumorigenesis.ResultsTMAO supplementation significantly reduced the colonic tumor load in male, but not female mice. Consistently, dietary TMAO resulted in higher retention of circulating TMAO in males, which was significantly and inversely correlated with tumor loads. Furthermore, TNF-α-expressing cell frequencies in the colonic intraepithelial lymphocytes (IEL) were significantly lower in TMAO-supplemented male mice compared to controls, suggesting that circulating TMAO could play a protective effect against colonic tumor growth via down-regulation of TNF-α-expressing cells. This was supported by in vitro observations that TMAO reduced lipopolysaccharides (LPS)-stimulated TNF-α production from macrophages. TMAO exerted no effects on cell proliferation (Ki67) and DNA damage (γH2AX) of HCT-116 cells.ConclusionOur study leads us to conclude that higher retention of circulating TMAO has a protective effect against CRC in a sex-dependent manner, highlighting the importance of understanding the complex relationship amongst the concentrations of host-microbial cometabolite TMAO, its systemic circulation, and its biological function in modulating CRC risk.
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Journal articleGranville NR, Williams JJ, Groner VP, et al., 2026,
Temperature mediates variation in avian sensitivity to forest cover.
, Nat Ecol EvolEmerging evidence shows that responses to deforestation can differ both across species and among populations of the same species. The reasons underlying these complex patterns are unclear, and this lack of clarity is a barrier to accurate monitoring and prediction of biodiversity change. Using data from 2,262 bird species across 7,326 sites from all forested continents, we show that between-species and within-species variations in responses to forest cover are mediated by temperature. Populations in warmer macroclimates tend to decline in incidence in deforested landscapes because hotter microclimates push them closer to their species' realized upper thermal tolerance limits. By contrast, populations in cooler macroclimates tend to be less affected by or even benefit from deforestation, as microclimatic temperatures are pushed closer to more optimal temperatures. Our findings offer an empirically grounded framework for biodiversity models that move beyond fixed species responses and incorporate interactions between temperature and land-use change.
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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 articleBergum M, Suthakaran S, Martin B, et al., 2026,
A liquid handling platform for standardised quantification of cell-free enzymatic activity encoded by antimicrobial resistance genes
, Synthetic Biology, Vol: 11, ISSN: 1939-7267Antimicrobial resistance (AMR) is a growing global threat to human health, and rapid methods for characterising emerging antimicrobial resistance genes (ARGs) are needed. Here, we develop a semi-automated workflow using cell-free gene expression (CFE) systems to measure the activity of two ARGs encoded on plasmid DNA that produce rifampicin-inactivating and gentamicin-inactivating enzymes. We validated the use of a small benchtop Myra liquid handling system compared to manual pipetting, with no statistical differences observed. After optimising the pre-incubation time of ARGs and dispensing protocol, expression of aac(3)-IIa increased the half-maximal inhibition concentration (IC50) of gentamicin by over 150-fold, while arr-3 increased the IC50 of rifampicin by approximately 20-fold compared to controls. This methodology for rapid, semi-automated ARG characterisation offers a strategy to combat AMR by assessing novel ARGs identified through genomic surveillance or profiling activity of new or derivative antibiotics.
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Journal articleMurray JW, 2026,
Random repeats open a route into folded protein space
, Proceedings of the National Academy of Sciences, Vol: 123, ISSN: 0027-8424 -
Journal articleLiu H, Prentice IC, Morfopoulos C, 2026,
Tracing Vegetation Stress from Space: Isoprene Emissions Capture the Spatiotemporal Footprint of El Niño
, npj Climate and Atmospheric Science, ISSN: 2397-3722El Niño events exert a profound influence on the global carbon cycle by imposing widespread heat and water stress on terrestrial ecosystems. Plant isoprene emissions respond rapidly to such stress, yet it remains unclear whether this response can track the spatiotemporal evolution of El Niño’s impacts over land. Here, we used satellite-derived global isoprene emissions for the first time to assess the west-east progression of the 2015–2016 El Niño. We observed that isoprene emissions increased by up to approximately 30% across tropical ecosystems relative to the climatological mean, with pronounced anomalies emerging during the event. The spatiotemporal evolution of these anomalies closely aligns with the El Niño progression inferred from sea surface temperature (SST) anomalies in the equatorial Pacific. In contrast, commonly used satellite vegetation products, including leaf area index (LAI) and solar-induced chlorophyll fluorescence (SIF), show weaker and spatially incoherent responses. These results demonstrate that satellite-derived isoprene provides a sensitive and mechanistically grounded tracer of ecosystem stress, offering a complementary perspective for monitoring the intensity and propagation of extreme climate events across terrestrial ecosystems.
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Journal articleBaizurah SN, Groner VP, 2026,
Conservation: When extremes meet rarity.
, Curr Biol, Vol: 36, Pages: R919-R921A catastrophic five-day rain triggered over 50,000 landslides across the core habitat of the critically endangered Tapanuli orangutan in Sumatra, potentially killing a significant proportion of the population and raising urgent questions about rare species' viability in a changing climate.
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Journal articleZhao Z, Vercellino I, Whitelegge JP, et al., 2026,
Cryo-EM structures of naturally occurring dimeric photosystem II complexes lacking the Mn₄CaO₅ cluster
, Nature Communications, Vol: 17, ISSN: 2041-1723Robust 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 report 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 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, Vol: 23, Pages: 5593-5605, 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 articleDi Domenico F, Kucharczyk MW, Patel R, et 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
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Journal articleKütahya C, Pániker CC, Ly F, et al., 2026,
Masterbatch-enabled acceleration of polyolefin biodegradation under open air terrestrial environmental conditions
, npj Materials Degradation, Vol: 10, ISSN: 2397-2106Polyolefins, commonly used in packaging and single-use products, are notoriously persistent in the environment, contributing significantly to environmental pollution. In scientific literature to date, polyolefins have not been reported to fully biodegrade. This study examines the biodegradation potential of polyolefin materials, specifically polyethylene (PE) and polypropylene (PP), enhanced through the incorporation of Biotransformation Masterbatch technology. The inclusion of the Biotransformation Masterbatch accelerated and enabled the full biodegradation of PE and PP, as demonstrated by laboratory weathering, and biodegradation studies in soil at mesophilic temperatures. Ecotoxicity tests revealed no adverse effects on test organisms in both soil and water environments, while metagenomics analysis demonstrated that biodegradation of these polyolefins did not significantly change the soil microbiota composition, which showed higher metabolic activity compared to virgin plastic controls. These findings demonstrate that Biotransformation technology provides an effective solution for delivering polyolefin-based materials with reduced environmental impact. It offers a sustainable alternative to conventional plastics, preserving the performance characteristics of traditional polyolefins while addressing the problem with fugitive plastic waste in the environment.
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Journal articleGhosh M, Goodman D, 2026,
Partial recurrence can enable robust and efficient computation
, Communications AI and computing, Vol: 1, ISSN: 3091-292XNeural 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 fully recurrent. 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.
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