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Quantitative, Systems & Engineering Biology Publications

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Quantitative, Systems & Engineering Biology

Engineered bacteriophages for therapeutic and diagnostic applications

Kandas Traore, Damien Seyer, Agnes Mihajlovski, Antonia P Sagona

Antimicrobial resistance represents one of the most serious threats to both public health and economic sustainability. One of the promising approaches to address this problem is phage therapy – treatment of pathogenic bacterial infections using bacteriophages. Bacteriophages have a narrow host spectrum of activity, minimal side effects and self-replication at the infection site, which positions them as promising candidates to complement or replace conventional antibiotics. Moreover, they can be easily genetically modified to enhance their effectiveness and safety. In this At a Glance article, we highlight the timely relevance of engineered phages as an innovative solution in a rapidly evolving healthcare landscape. First, we introduce bacteriophages' life cycle, ecology and therapeutic history, emphasizing their role in One Health strategies. Then, we describe advanced engineering techniques that can be used to expand bacteriophages' functionalities. Finally, we discuss innovative applications of engineered bacteriophages in biotechnological applications and as a potential countermeasure for antimicrobial resistance, including serving as a shuttle for delivering genes and drugs to the targeted bacterial and eukaryotic cells, targeting intracellular bacteria, contributing to vaccine development, facilitating advancements in tissue engineering and improving bacteriophages' antibacterial properties.

Disease Models and Mechanisms, September 2025

Developmental fates and N2-fixing efficiency of terminally-differentiated versus undifferentiated bacteroids from legume nodules

Carmen Sánchez-Cañizares , Raphael Ledermann , Joseph McKenna, Thomas J Underwood , Marcela Mendoza-Suárez , Rob Green , Karunakaran Ramakrishnan , Alison K East , Isabel Webb , Charlotte Kirchhelle , Beatriz Jorrín , Gerhard Saalbach , Euan K James , Flavia Moreira-Leite , Jason Terpolilli , Philip S Poole

Within legume root nodules, rhizobia differentiate into bacteroids, which reduce N2 into NH3 for secretion to the plant. Bacteroids may be swollen and terminally differentiated or non-swollen and can regenerate outside nodules. It is unclear why these different endosymbiotic lifestyles exist and whether they differ in symbiotic efficiency. Here, we compared N2 fixing bacteroids of the near isogenic strains Rhizobium leguminosarum bv. phaseoli 4292 (Rlp4292) and R. leguminosarum bv. viciae A34 (RlvA34), nodulating Phaseolus vulgaris (common bean) and Pisum sativum (pea), respectively. The larger bean plants fixed more N2, but peas fixed 1.6-3-fold more per unit nodule mass. Values per unit volume were similar between bean and pea because bean nodules are 2.7-fold denser (i.e., mass per unit volume). Bean nodules have higher numbers of smaller (∼1/5 the volume) bacteroids than peas. Bean bacteroids are denser (i.e., 2.5-fold protein per unit volume) although less closely packed than pea bacteroids (i.e. more space between bean bacteroids). Critically, pea bacteroids, fix N2 at higher rates versus bean per unit bacteroid protein, as protein expression is skewed towards N2 fixation and TCA-cycle enzymes. Pea bacteroids infect 1.6 times the percentage of nodule volume of beans (i.e., 14.2% versus 9.1%). Overall, the increased packing density of pea bacteroids, as well as the bias of their proteome to nitrogenase, associated N2 fixation processes, and dicarboxylate metabolism, contributes to their greater symbiotic efficiency, which is likely driven by plant antimicrobial peptides.

Plant Physiology, December 2025

Unlocking plant health survey data: An approach to quantify the sensitivity and specificity of visual inspections

Matt Combes, Nathan Brown, Robin N. Thompson, Alexander Mastin, Peter Crow, Stephen Parnell

Invasive plant pests and pathogens cause substantial environmental and economic damage. Visual inspection remains a central tenet of plant health surveys, but its sensitivity (probability of correctly identifying the presence of a pest) and specificity (probability of correctly identifying the absence of a pest) are not routinely quantified. As knowing sensitivity and specificity of visual inspection is critical for effective contingency planning and outbreak management, we address this deficiency using empirical data and statistical analyses. Twenty-three citizen scientist surveyors assessed up to 175 labelled oak trees for three symptoms of acute oak decline. The same trees were also assessed by an expert who has monitored these individual trees annually for over a decade. The sensitivity and specificity of surveyors was calculated using the expert data as the ‘gold-standard’ (i.e., assuming perfect sensitivity and specificity). The utility of an approach using Bayesian modelling to estimate the sensitivity and specificity of visual inspection in the absence of a rarely available ‘gold-standard’ dataset was then examined with simulated plant health survey datasets. There was large variation in sensitivity and specificity between surveyors and between different symptoms, although the sensitivity of detecting a symptom was positively related to the frequency of the symptom on a tree. By leveraging surveyor observations of two symptoms from a minimum of 80 trees on two sites, with reliable prior knowledge of sites with a higher (~0.6) and lower (~0.3) true disease prevalence we show that sensitivity and specificity can be estimated without ‘gold-standard’ data using Bayesian modelling. We highlight that sensitivity and specificity will depend on the symptoms of a pest or disease, the individual surveyor, and the survey protocol. This has consequences for how surveys are designed to detect and monitor outbreaks, as well as the interpretation of survey data that is used to inform outbreak management.

PLOS - Computational Biology, November 2025

Updated Priorities for Cerebroprotection Trials

Sean Savitz, Edgar Samaniego, David Liebeskind, Johannes Boltze

A STAIR XIII workshop was held to discuss aspects of trials likely to have the greatest impact on detecting meaningful treatment effects of cerebroprotection in acute stroke. Intended goals for hyperacute protection should be focused on preserving penumbral tissue and delaying infarct core growth to augment the impact of reperfusion therapies. Infarct volume is a biologically and clinically meaningful surrogate imaging marker to assess the treatment effects of cerebroprotection. Lastly, clinical outcome measures for cerebroprotection should include domain-specific and patient-centered outcomes to detect clinically meaningful changes across multiple functional domains.

Stroke, November 2025

Perspectives from a Workshop: Intelligent Assessment in the age of Artificial Intelligence

Matt Bawn, Nigel Francis, Liz Alvey, Christopher Hassall, Andre Pires-daSilva, Pedro Barra, Denise Hough, Hannah Campbell, Matt Hardy, Juanvi Canet-Perez

The advent of Generative Artificial Intelligence (GenAI) is already impacting pedagogic strategies and assessment methodologies in higher education, particularly in the biological sciences which have traditionally relied heavily on written assessments. GenAI's rapid and plausible text generation capabilities challenge traditional written assessments and prompt a shift towards more authentic assessment types. This paper explores innovative applications of GenAI in biology education through case studies presented at a recent workshop. These case studies illustrate how GenAI has the potential to enhance academic activities, from developing learning resources to fostering student engagement through active learning strategies. The discussion highlights a shift from product-oriented assessments to process-oriented approaches that prioritize continuous interaction, iteration, and reflection among learners. Despite GenAI's reliance on pre-existing data raising concerns about originality and contextual accuracy, and its limitations in tasks requiring high creativity and deep understanding, it has the potential to enhance educational practices when applied with awareness of its constraints. The paper concludes with a balanced analysis of the transformative impact and inherent challenges of integrating GenAI into biology education, advocating for thoughtful implementation to ensure it augments rather than replaces traditional teaching methods.

Advances in Physiology Education- November 2025

PRC1-mediated H2A.Zub promotes gene expression by preventing H3.1K27me1 incorporation in Arabidopsis

Fernando Baile, Javier Antúnez-Sánchez, Jose Gutierrez-Marcos, Myriam Calonje

Background: PcG complexes are pivotal in orchestrating the transition from embryonic to vegetative development in plants. However, the mechanisms underlying the gene expression reprogramming that takes place during this developmental transition are still not fully understood. Several studies suggest that incorporating PcG modifications into distinct histone variants may play a key role in this process. However, while PRC2-mediated H3K27me3 is essential for gene repression, the timing of PRC2 action on canonical H3.1 or variant H3.3 remains unclear. Furthermore, the exact role of PRC1 in transcriptional regulation is still unresolved, partly owing to limited knowledge of the conditions under which this complex monoubiquitinates canonical H2A or H2A.Z variant.

Results: Here, we demonstrate that H2A.Z undergoes monoubiquitination during the seed-to-seedling transition. H2A.Zub facilitates the recruitment of PRC2 to mediate H3.3 trimethylation, repressing seed-specific genes; however, H2A.Zub also promotes the activation of vegetative-specific genes by preventing H3K27me1 incorporation into H3.1. Notably, the histone demethylase REF6 initiates this process by removing two methyl groups from stably repressed H3.1K27me3-marked genes, enabling the subsequent H2A.Zub incorporation. This result suggests that REF6 activity is a critical early step in PRC1-mediated transcriptional activation.

Conclusions: Our findings reveal the long-sought mechanism by which PRC1 participates in transcriptional activation. We demonstrate that PRC1-mediated H2A.Zub, acting as a “switcher”, plays a pivotal role in reprogramming active and repressed genes during the transition from embryonic to vegetative development. Moreover, our results provide new insights into the intricate relationship between histone modifications and histone variants in reprogramming and maintaining gene expression patterns.

Genome Biology, November 2025

Bee-mediated delivery of bacteriophage for biocontrol of the cherry canker pathogen Pseudomonas syringae pv. syringae

Shannon F. Greer, Sneha Chakravorty, Kieran Cooney-Nutley, Dave Chandler*, Gregory Firth, Rajesh Odedra, Mojgan Rabiey

Bacteriophages, phages or viruses that specifically infect bacteria, have shown promise for the biocontrol of bacterial plant diseases. However, one of the main challenges of using phages in agricultural systems is their precision application, being able to deliver an effective dose to the site of bacterial infection. In this study, a series of artificial and real cherry flower experiments was conducted to test whether commercially managed bumblebees (Bombus terrestris audax) could deliver phage effective against the cherry canker pathogen Pseudomonas syringae pv. syringae (Pss). Freeze-dried phage powder was formulated with powdered-skimmed milk and when tested, was found to retain viability for seven days in artificial bee feed after storage at 4 °C, room temperature or under glasshouse conditions. In both artificial and cherry flower experiments, bees successfully transferred the formulated phage from their hive to up to 88 % of flowers, resulting in significant reduction in Pss populations. Bees were also able to transfer phage between cherry flowers. The application of phages disrupted the cycle of Pss transmission by bees. These results highlight the potential of bee-mediated phage delivery as an effective biocontrol strategy against floral pathogens like Pss.

Biological Control, December 2025

Genomic insights into the ecological versatility of Tetracladium spp.

Anna Lazar, Fabrizio Alberti, George Muscatt, Ryan M. Mushinski, Christopher Quince, Gary D. Bending

Background: Tetracladium spp. represent a group of fungi that inhabit various ecological niches, including soil and aquatic environments, where they are considered to have a saprotrophic lifestyle and within plant roots as endophytes. To date, a lack of sequenced Tetracladium spp. genomes has inhibited our understanding of their metabolic potential and ecological interactions. In this study, we aimed to elucidate the genetic differences between aquatic saprotrophic and endophytic strains of Tetracladium spp. by sequencing and analysing the genomes of T. maxilliforme (isolated from Brassica napus roots) and T. marchalianum (isolated from freshwater), alongside 41 publicly available saprotrophic and endophytic Ascomycetes.

Results: Genomic sequencing revealed that T. maxilliforme possesses a genome size of 35.5 Mbp with 9657 predicted genes, while T. marchalianum has a genome size of 33.2 Mbp with 15,230 predicted genes. Our analyses primarily focused on carbohydrate-active enzymes (CAZymes). Both genomes possessed the full range of enzymatic machinery for cellulose degradation, as well as the complete repertoire of genes necessary to degrade plant cell walls. Notably, the genomes lacked essential enzymes for lignin degradation or modification. Furthermore, we observed a complete repertoire of known fungal chitin-degrading enzymes in both genomes, which might be related to potential interactions with other fungi. Enzyme composition profiles revealed distinct groupings, with T. maxilliforme primarily clustering with endophytic or ecologically versatile species, while T. marchalianum was predominantly associated with saprotrophic species. We also identified secondary metabolite biosynthetic gene clusters in both genomes, including several that showed high homology to those of known bioactive compounds.

Conclusions: In summary, our findings offer valuable insights into the genomic adaptations of Tetracladium spp. to various ecological niches, highlighting their enzymatic capabilities for carbohydrate degradation and potential interactions within fungal communities.

BMC Genomics, November 2025

The Use of Ecoacoustics to Monitor Soil Ecology: A Critical Review With Reference to Earthworms

Jacqueline L. Stroud, Michał K. Kalkowski, Kirsty L. Hassall, Miriam Treadway, Jessica Fannon, Aidan Keith, Siul Ruiz, Keith Attenborough

The use of ecoacoustics to monitor soil ecology was identified as a priority in the 2024 horizon scan of global biological conservation issues. Proponents suggest it will have societal impacts by improving soil health assessments, enhance soil biodiversity monitoring and facilitate the conservation, remediation and management of soil ecosystems. Here we review soil ecoacoustics in terms of its definition, theoretical basis, acoustic indices and statistical inferences. To do this we explain mechanical wave behaviour, mechanoreception by fauna, and tactical signal design with reference to earthworms as ecosystem engineers. Ecoacoustics emerged from research on animal long‐distance communication systems, and its direct application to soils has been identified as a problem area. A new field within ecoacoustics has been created for soils, sonoscape investigations, to capture spatio‐temporal complexity of ecological features (rather than soil ecology). There is a good case for reclassifying soil ecoacoustic ‘soundscape’ studies as sonoscapes. We identify that further refinement of ecoacoustics is required for applications to soil habitats. The performance of sonoscape investigations is dependent on acoustic indices and statistical inferences, and we question why stationary signal processing is used as the base transform for soils data, and highlight the issue of unbalanced data sets, particularly pertinent to soils as there is limited understanding of what exactly is being detected. We list the key research needs and highlight that integrating soil science and mechanistic modelling of soil processes and wave propagation as an essential component of developing reliable monitoring solutions. Embracing these interdisciplinary avenues will help develop sensing capabilities for soils in robust scientific principles and mitigate the risks of speculative overreach.

European Journal of Soil Science, November 2025

Maximizing the Biocontrol Potential of Bacteriophages: A Call for Critically-Needed Field Research

George W Sundin, Sara M Villani, Quan Zeng, Michelle Hulin, Mojgan Rabiey, Kerik Cox

Bacteriophages are viruses capable of infecting bacterial cells. Lytic phages, which infect and kill bacterial cells, are of interest in disease management in human, animal, and plant systems. In plant pathology, the biocontrol of bacterial diseases is of heightened interest because of the lack of efficacious options in many pathosystems. Numerous papers have been published in the past few decades on phage that target plant pathogenic bacteria, and a large majority of these have been focused on phage isolation and characteristics that highlight the promise and potential of phage as biocontrol agents. In contrast, relatively few of these papers have reported results from studies conducted in the field. Of the recent papers (2022 to 2025) reporting field studies, disease efficacy results are inconsistent. We argue that field studies should be an essential component of phage biocontrol research to understand how to best utilize and deploy phages to generate consistently effective disease management.

Plant Disease, November 2025.

Comparative genomic analysis of a metagenome-assembled genome reveals distinctive symbiotic traits in a Mucoromycotina fine root endophyte arbuscular mycorrhizal fungus

Joshua Cole, Sébastien Raguideau, Payman Abbaszadeh-Dahaji, Sally Hilton, George Muscatt, Ryan M. Mushinski, R. Henrik Nilsson, Megan H. Ryan, Christopher Quince, Gary D. Bending

Background: Recent evidence shows that arbuscular mycorrhizal (AM) symbiosis, as defined by the presence of arbuscules, is established by two distinct fungal groups, with the distinctive ‘fine root endophyte’ morphotype formed by fungi from the subphylum Mucoromycotina rather than the sub-phylum Glomeromycotina. While FRE forming fungi are globally distributed, there is currently no understanding of the genomic basis for their symbiosis or how this symbiosis compares to that of other mycorrhizal symbionts.

Results: We used culture-independent metagenome sequencing to assemble and characterise the metagenome-assembled genome (MAG) of a putative arbuscule forming fine root endophyte, which we show belonged to the family Planticonsortiaceae within the order Densosporales. The MAG shares key traits with Glomeromycotina fungi, which indicate obligate biotrophy, including the absence of fatty acid and thiamine biosynthesis pathways, limited enzymatic abilities to degrade plant cell walls, and a high abundance of calcium transporters. In contrast to Glomeromycotina fungi, it exhibits a higher capacity for degradation of microbial cell walls, a complete cellulose degradation pathway, low abundances of copper, nitrate and ammonium transporters, and a complete pathway for vitamin B6 biosynthesis.

Conclusion: These differences, particularly those typically associated with saprotrophic functions, highlight the potential for contrasting interactions between Mucoromycotina and Glomeromycotina fungi with their host plant and the environment. In turn, this could support niche differentiation in resource acquisition and complementary ecological functions.

BMC Genormics, October 2025

The 2025 report of the Lancet Countdown on health and climate change

Marina Romanello, Maria Walawender, Shih-Che Hsu, Annalyse Moskeland, Yasna Palmeiro-Silva, Daniel Scamman, James W Smallcombe, Sabah Abdullah, Melanie Ades, Abdullah Al-Maruf, Nadia Ameli, Denitsa Angelova, Sonja Ayeb-Karlsson, Joan Ballester, Xavier Basagaña, Hannah Bechara, Paul J Beggs, Wenjia Cai, Diarmid Campbell-Lendrum, Gina E C Charnley, Orin Courtenay, Troy J Cross, Carole Dalin, Niheer Dasandi, Shouro Dasgupta, Michael Davies, Matthew Eckelman, Chris Freyberg, Paulina Garcia Corral, Olga Gasparyan, Joseph Giguere, Georgiana Gordon-Strachan, Sophie Gumy, Samuel H Gunther, Ian Hamilton, Yun Hang, Risto Hänninen, Stella Hartinger, Kehan He, Julian Heidecke, Jeremy J Hess, Slava Jankin, Ollie Jay, Dafni Kalatzi Pantera, Ilan Kelman, Harry Kennard, Gregor Kiesewetter, Patrick Kinney, Dominic Kniveton, Vally Koubi, Rostislav Kouznetsov, Pete Lampard, Jason K W Lee, Bruno Lemke, Bo Li, Andrew Linke, Yang Liu, Zhao Liu, Rachel Lowe , Siqi Ma, Tafadzwanashe Mabhaudhi, Carla Maia, Anil Markandya, Greta Martin, Jaime Martinez-Urtaza, Mark Maslin, Lucy McAllister, Celia McMichael, Zhifu Mi, James Milner, Kelton Minor, Jan Minx, Nahid Mohajeri, Natalie C Momen, Maziar Moradi-Lakeh, Karyn Morrisey, Simon Munzert, Kris A Murray, Nick Obradovich, Papa Orgen, Matthias Otto, Fereidoon Owfi, Olivia L Pearman, Frank Pega, Andrew J Pershing, Ana-Catarina Pinho-Gomes, Jamie Ponmattam, Mahnaz Rabbaniha, Tim Repke, Jorge Roa, Elizabeth Robinson, Joacim Rocklöv, David Rojas-Rueda, Jorge Ruiz-Cabrejos, Matilde Rusticucci, Renee N Salas, Adrià San José Plana, Jan C Semenza, Jodi D Sherman, Joy Shumake-Guillemot, Pratik Singh, Henrik Sjödin, Matthew R Smith, Mikhail Sofiev, Cecilia Sorensen, Marco Springmann, Jennifer D Stowell, Meisam Tabatabaei, Federico Tartarini, Jonathon Taylor, Cathryn Tonne, Marina Treskova, Joaquin A Trinanes, Andreas Uppstu, Nicolas Valdes-Ortega, Fabian Wagner, Nick Watts, Hannah Whitcombe, Richard Wood, Pu Yang, Ying Zhang, Shaohui Zhang, Chi Zhang, Shihui Zhang, Qiao Zhu, Peng Gong, Hugh Montgomery, Anthony Costello

Driven by human-caused greenhouse gas emissions, climate change is increasingly claiming lives and harming people's health worldwide. Mean annual temperatures exceeded 1·5°C above those of pre-industrial times for the first time in 2024. Despite ever more urgent calls to tackle climate change, greenhouse gas emissions rose to record levels that same year. Climate change is increasingly destabilising the planetary systems and environmental conditions on which human life depends.

The Lancet, October 2025

iNOME-seq: in vivo simultaneous genome-wide mapping of chromatin accessibility, nucleosome positioning, DNA-binding protein sites, and DNA methylation in Arabidopsis

Nosheen Hussain, Ryan Merrit, Julia Engelhorn, Javier Antunez-Sanchez, Anjar Wibowo, David Latrasse, Travis Wrightsman, Maximillian Collenberg, Ilja Bezrukov, Hidayah Alotaibi, Elsa Carrasco, Moussa Benhamed, Detlef Weigel, Nicolae Radu Zabet, Jose Gutierrez-Marcos

We present iNOMe-seq, a novel method for in vivo simultaneous profiling of chromatin accessibility, nucleosome occupancy, DNA-binding protein sites, and DNA methylation in living tissues. iNOMe-seq utilizes an m5C methyltransferase to mark accessible cytosines in a GpC context, bypassing nucleosome-restricted regions. Using Arabidopsis thaliana, we demonstrate that iNOMe-seq improves chromatin accessibility quantification compared to existing methods. Furthermore, it allows for the spatial and temporal analysis of chromatin dynamics, transcription factor binding, and DNA methylation, offering insight into the role of epigenetic components in transcriptional regulation across tissues and genetic variations in natural populations.

Genome Biology, October 2025

Structural characterization of the YbbAP-TesA ABC transporter identifies it as a lipid hydrolase complex that extracts hydrophobic compounds from the bacterial inner membrane

McAndrew, Martin B. L., Cook, Jonathan P., Gill, Amy, Sahoo, Kavya, Thomas, Clare, Stansfeld, Phillip J. and Crow, Allister

Type VII ABC transporters are ATP-powered membrane protein complexes that drive key biological processes in the bacterial cell envelope. In Escherichia coli, three of the four Type VII ABC systems have been extensively characterized, including: the FtsEX-EnvC cell division complex, the LolCDE-LolA lipoprotein trafficking machinery, and the MacAB-TolC efflux pump. Here we describe a fourth E. coli Type VII ABC system, YbbAP-TesA, which combines a Type VII ABC transporter with a multifunctional hydrolytic enzyme. Structures of the complete YbbAP-TesA complex, and of YbbAP with and without bound ATP analogues, capture implied long-range transmembrane conformational changes that are the hallmark of this ABC superfamily’s mechanotransmission mechanism. We further show that YbbAP-TesA can hydrolyze a variety of ester and thioester substrates and experimentally confirm a constellation of active site residues in TesA. Our data suggests YbbAP has a role in extracting hydrophobic molecules from the inner membrane and presenting these to TesA for hydrolysis. The work extends collective knowledge of the remarkable diversity of the ABC superfamily and establishes a new function for Type VII ABC transporters in bacterial cells.

PLOS Biology, November 2025

Identification of Race-Specific, Clade-Specific and Broad-Spectrum Resistance to Xanthomonas campestris pv. campestris in Brassica Diversity Fixed Foundation Sets

Shannon F. Greer, Jamie Harrison, Daisy Bown, Maria Serrano, Rana Muhammed Fraz Hussain, Srayan Ghosh, Graham R. Teakle, Vardis Ntoukakis, David J. Studholme, Joana G. Vicente, Murray Grant

Black rot, caused by Xanthomonas campestris pv. campestris (Xcc), is the most damaging bacterial disease of vegetable brassicas (Brassica oleracea) worldwide. The prevalence of several genetically diverse Xcc races makes breeding for varietal resistance challenging. In this study, we have screened diversity fixed foundation sets (DFFSs) of B. oleracea and Brassica napus for resistance against isolates belonging to prevalent Xcc races 1, 4, 5 and 6. The DFFSs are designed to capture the genetic diversity available within the respective Brassica species gene-pools in smaller subsets of lines. Our findings revealed that resistances to race 1 and 4 were largely absent in B. oleracea but more prevalent in B. napus. Notably, resistance to race 4 was particularly common in B. napus (63% of lines showed resistance, 13% of lines showed partial resistance). Conversely, resistance to races 5 and 6 was more common in B. oleracea than in B. napus. In B. oleracea, there was no significant association between disease index and morphotype but, among the B. napus morphotypes, swede was the most susceptible to races 1, 5 and 6 but not to race 4. Ten B. oleracea and 67 B. napus lines showed resistance to more than one isolate. Further testing of a subset of these lines demonstrated that resistances were effective against additional diverse Xcc isolates in a race-specific, clade-specific or broad-spectrum manner. The resistant lines identified in this study offer a valuable resource for breeding programmes aimed to achieve durable and sustainable control of Xcc.

Plant Pathology, October 2025

Enset Bacterial Wilt (Xanthomonas vasicola pv. musacearum): Farmer Perspectives, Physicochemical Characterization, and Phenotypic Variation Among Strains

Tafesse Kibatu, Sebsebe Demissew, Diriba Muleta, Getahun Haile, Seman Abrar, Denberu Kebede, Murray Grant, Sadik Muzemil, Tileye Feyissa

Enset is a staple food for approximately 25% of Ethiopia’s population. It is threatened by a range of biotic and abiotic stress, of which bacterial wilt is the most significant. This study investigated the enset bacterial wilt (EBW) status on farms in Gedeo, Kembata Tembaro, Gurage, Hadiya zones, and the Basketo special woreda of Southern Ethiopia. In addition, infected enset plant samples were collected from Hadiya, Kembata Tembaro, and Gedeo zones to assess bacterial strain diversity using physicochemical and morphological approaches. Representative Kebeles were selected using purposive sampling based on their agroecological conditions. Data was collected through in-depth interviews, questionnaires, group discussions, and field observation. The morphology of bacterial wilt isolates was characterized by color, texture, form, elevation, margin, and motility. In addition, a combination of oxidase, aesculin hydrolysis, catalase, gram reaction, hydrogen sulfide (H2S), gelatin liquefaction, and fructose, lactose, mannitol, and sorbitol utilization tests were conducted to capture physiochemical differences. Tolerance to salt and high temperatures was also evaluated. The bacterial wilt impact varies significantly across enset growing regions, with highlands experiencing the highest. This research emphasizes the importance of assessing both spatial and temporal variation, as well as integrating local knowledge and robust scientific approaches for effective bacterial wilt management and enset landrace conservation efforts. The research also provides valuable insights into the characteristics of bacterial wilt isolates in Southern Ethiopia. Analyses of morphology, potassium hydroxide solubility, catalase activity, and carbohydrate utilization were consistent, however, variations in bacterial isolates response to tests of easculin, oxidase, gelatin liquid, H2S tests and response to osmotic and temperature exposures. This study reveals a strong association between the bacterial wilt effect and the enset growing regions. EBW exhibits seasonal fluctuations. Bacterial wilt isolates displayed consistent morphological characteristics. All isolates similarly utilized sorbitol, mannitol, lactose, and fructose carbohydrates. All isolates exhibited positive potassium hydroxide solubility and catalase activity. However, the isolates displayed variations in responses to easculin, oxidase, gelatin liquefaction, and H2S production. The isolates also displayed variations in tolerance to salt and high temperatures. These variations can be valuable for understanding disease epidemiology and management.

Advances in Agriculture, January 2025

Between‐country differences in the psychosocial profiles of British cattle farmers

Naomi S. Prosser, Eamonn Ferguson, Jasmeet Kaler, Edward M. Hill, Michael J. Tildesley, Matt J. Keeling, Martin J. Green

BACKGROUND: Psychosocial factors are important for the uptake of livestock disease control measures by farmers and can differ by region, which would have implications for disease control nationally.

METHODS: We investigated altruism, trust, psychological proximity and the COM-B behaviour change framework in a survey of 475 British cattle farmers in 2020. Using regression models, we studied associations between the country farmers lived in and psychosocial and behaviour change factors. RESULTS: There were many between-country differences in farmers' psychosocial and COM-B profiles. Accounting for multiple tests, Scottish cattle farmers reported higher trust in governmental judgements for disease control and greater social opportunity to control disease than English cattle farmers.

LIMITATIONS: There were relatively low numbers of respondents from Scotland and Wales. As such, the results should be interpreted with caution. Northern Irish farmers could not be included in the analyses as there were too few responses.

CONCLUSION: Cattle farmers differed in their psychosocial profiles by country. Our sample of Scottish farmers reported higher trust in, and felt better supported by, government in the context of disease control than the English farmers, which could be due to different disease control approaches between devolved governments. Understanding between-country differences in farmer psychosocial attributes has implications for animal health governance and approaches to disease control.

Veterinary Record, October 2025

Mechanisms of permselectivity of connexin hemichannels to small molecules

Alexandra Lovatt, Jack Butler, Nicholas Dale

Connexins can act either as hemichannels to facilitate ion and small-molecule movement from the cytosol to the extracellular space or as gap junction channels to provide a pathway for solute exchange between cells. Connexins are ubiquitously expressed throughout the body and are implicated in a wide range of processes. The permselectivity of connexin hemichannels for small neurochemicals remains poorly understood. By coexpressing genetically encoded fluorescent sensors for ATP, glutamate, and lactate with a range of connexins, we examined the ability of different hemichannels to permit the release of these compounds under physiological conditions and in response to physiological stimuli (small changes in partial pressure of CO2 and transmembrane depolarization). We found that some connexin hemichannels were relatively nonselective (Cx26, Cx32, Cx43, and Cx31.1) allowing passage of ATP, glutamate, and lactate. By contrast, other connexin hemichannels (Cx36, Cx46, and Cx50) were highly selective. Cx36 and Cx46 hemichannels allowed the release of ATP but not glutamate or lactate. The size of the permeating molecule cannot be the sole determinant of permselectivity. By contrast, Cx50 hemichannels permitted the release of lactate and glutamate but not ATP. We also found that the nature of the opening stimulus could alter the permselectivity of the hemichannel—for some of the relatively nonselective connexins, hemichannel opening via depolarization was ineffective at allowing the release of lactate. By performing a mutational analysis, informed by the differential selectivity of the closely related Cx46 and Cx50 hemichannels, we found that the charge on the N terminus and N terminus–transmembrane 2 interactions are key contributors to permselectivity for ATP.

Journal of Biological Chemistry, December 2025

Discovery of Late Intermediates in Methylenomycin Biosynthesis Active against Drug-Resistant Gram-Positive Bacterial Pathogens

Christophe Corre, Gideon A. Idowu, Lijiang Song, Melanie E. Whitehead, Lona M. Alkhalaf, Gregory L. Challis

The methylenomycins are highly functionalized cyclopentanone antibiotics produced by Streptomyces coelicolor A3(2). A biosynthetic pathway to the methylenomycins has been proposed based on sequence analysis of the proteins encoded by the methylenomycin biosynthetic gene cluster and the incorporation of labeled precursors. However, the roles played by putative biosynthetic enzymes remain experimentally uninvestigated. Here, the biosynthetic functions of enzymes encoded by mmyD, mmyO, mmyF, and mmyE were investigated by creating in-frame deletions in each gene and investigating the effect on methylenomycin production. No methylenomycin-related metabolites were produced by the mmyD mutant, consistent with the proposed role of MmyD in an early biosynthetic step. The production of methylenomycin A, but not methylenomycin C, was abolished in the mmyF and mmyO mutants, consistent with the corresponding enzymes catalyzing the epoxidation of methylenomycin C, as previously proposed. Expression of mmyF and mmyO in a S. coelicolor M145 derivative engineered to express mmr, which confers methylenomycin resistance, enabled the resulting strain to convert methylenomycin C to methylenomycin A, confirming this hypothesis. A novel metabolite (premethylenomycin C), which readily cyclizes to form the corresponding butanolide (premethylenomycin C lactone), accumulated in the mmyE mutant, indicating the corresponding enzyme is involved in introducing the exomethylene group into methylenomycin C. Remarkably, both premethylenomycin C and its lactone precursor were one to two orders of magnitude more active against various Gram-positive bacteria, including antibiotic-resistant Staphylococcus aureus and Enterococcus faecium isolates, than methylenomycins A and C, providing a promising starting point for the development of novel antibiotics to combat antimicrobial resistance.

Journal of the American Chemical Society, October 2025

Protein Target Highlights in CASP16: Insights From the Structure Providers

Leila T. Alexander, Océane M. Follonier, Andriy Kryshtafovych,| Kim Abesamis, Sabrina Bibi-Triki, Henry G. Box, Cécile Breyton, Françoise Bringel, Loic Carrique, Alessio d'Acapito, Gang Dong, Rebecca DuBois, Deborah Fass, JulianaMartinez Fiesco, Daniel R. Fox, Jonathan M. Grimes, Rhys Grinter, Matthew Jenkins, Roman Kamyshinsky, Jeremy R. Keown, Gerald Lackner, Michael Lammers, Shiheng Liu, Andrew L. Lovering,Tomas Malinauskas, Benoît Masquida, Gottfried J. Palm, Christian Siebold,Tiantian Su, Ping Zhang, Z. Hong Zhou, Krzysztof Fidelis, Maya Topf, John Moult, Torsten Schwed

This article presents an in-depth analysis of selected CASP16 targets, with a focus on their biological and functional significance. The authors highlight the most relevant features of the target proteins and discuss how well these were reproduced in the submitted predictions. While the overall performance of structure prediction methods remains impressive, challenges persist, particularly in modeling rare structural motifs, flexible regions, small molecule interactions, posttranslational modifications, and biologically important interfaces. Addressing these limitations can strengthen the role of structure prediction in complementing experimental efforts and advancing both basic research and biomedical applications.

Proteins (Structure, Function, Bioinformatics), October 2025

StayRose: A photostable StayGold derivative redshifted by genetic code expansion

Will Scott, Esther Ivorra-Molla, Dipayan Akhuli, Teresa Massam-Wu, Pawel K. Lysyganicz, Rylie Walsh, Matthew Parent, Jonathan Cook, Lijiang Song, Abhishek Kumar, Falk Schneider, Masanori Mishima, Allister Crow, Mohan K. Balasubramanian

Photobleaching of fluorescent proteins often limits the acquisition of high-quality images in microscopy. StayGold, a novel dimeric GFP recently monomerized through sequence engineering, addresses this challenge with its high photostability. There is now a focus on producing different colored StayGold derivatives to facilitate concurrent tagging of multiple targets. The unnatural amino acid 3-aminotyrosine has previously been shown to redshift superfolder GFP upon incorporation into its chromophore via genetic code expansion. Here, we apply the same strategy to redshift StayGold through substitution of tyrosine-58 with 3-aminotyrosine. The resultant red fluorescent protein, StayRose, shows an excitation wavelength maximum of 530 nm and an emission wavelength maximum of 588 nm. Importantly, the monomeric mStayRose retains the favorable photostability in vivo in Escherichia coli and zebrafish embryos. A high-resolution crystal structure of StayRose confirms the modified structure of the amino chromophore within an unperturbed 3D fold. Although reliant on genetic code expansion, StayRose provides an important step toward developing redshifted StayGold derivatives.

Journal of Biological Chemistry, December 2025

Better understanding complex pathomechanisms in central nervous system disorders as a prerequisite for improved diagnostic and therapeutic approaches

Piotr Walczak, Shen Li, Xumming Ji, Johannes Boltze

Central nervous system (CNS) disorders are usually characterized by a complex pathophysiology. The last issue of Neuroprotection featured reviews and research articles looking at peripheral factors such as the gut microbiome or a history of pre-eclampsia and their impact on CNS conditions. Articles presented in the current issue of Neuroprotection will shift the focus back to the CNS but will continue to provide insights from recent research that help to better understand the pathophysiological complexity of CNS conditions.

Neuroinflammation is known to be a hallmark and major contributor to many CNS diseases. It comprises both peripheral and central immune cells and can be modulated by frequent comorbidities such as hypertension. Moreover, neuroinflammatory processes can involve cell populations not primarily characterized as immune cells. Psychiatric conditions, including major depressive disorders (MDD), are increasingly recognized to be linked to neuroinflammation but also to systemic comorbidities, stress and aging. A better understanding of neuroinflammatory processes in the context of psychiatric conditions may help to identify novel therapeutic targets for better and potentially causal treatment strategies.

Neuroprotection, September 2025

Development of biological soil crusts at the soil surface influences the persistence and movement of crop protection products

Laurence Hand, Mark C.J. Day, Carol Nichols, Hendrik Schäfer, Samantha Marshall, Gary D. Bending

Laboratory soil biodegradation studies required for approval of crop protection products (CPPs) are performed under continuous darkness, nullifying any potential contributions of algal and moss dominated biological soil crusts (BSC). There is growing evidence for metabolism of CPPs by phototrophic microorganisms under laboratory conditions, but limited data is available under field conditions. In this study we investigated the impact of the BSC on the fate of two 14C-fungicides under semi-field conditions using different light filters to alter formation of the BSC by exclusion/transmission of UV and photosynthetically active (PAR) wavelengths. Attenuation of PAR light significantly reduced formation of a BSC, which resulted in a significant slowing of the dissipation of benzovindiflupyr, which is known to be susceptible to phototrophic metabolism in aquatic systems, with 12–14 % more parent compound remaining at the end of the study when BSC development was impeded. For paclobutrazol, however, no significant difference in dissipation rate was observed. For both compounds there was significantly less non-extractable residue (NER) formation when BSC development was impeded (4–9 % reduction). Additionally, for both fungicides, the presence of a viable BSC resulted in 10–20 % more movement through the surface 5 mm of the soil, although this effect was limited to the period immediately after application and was likely due to increased porosity of the surface layer. This study confirms that the presence of phototrophs can significantly impact the environmental fate of CPPs on the surface of agricultural fields, either directly through metabolism or indirectly by altering the properties of the surface layer.

Science of The Total Environment November 2025

Population genetics show that aphids (Hemiptera: Aphididae) are limited by summer host-plant distribution at the regional scale

Dion Garrett, Graham Teakle, Rosemary Collier, James R Bell, Ramiro Morales-Hojas

Nasonovia ribisnigri (Mosley) is a severe aphid pest of outdoor lettuce, and the combination of sporadic and unpredictable colonization on outdoor lettuce, along with the breakdown of cultivar resistance, has left few effective control methods. The population structure (spatially and temporally) of N. ribisnigri is currently unknown in England, and therefore microsatellite markers were designed to estimate the impacts of host plant selection pressure (including host plant resistance) and environmental change. Biological samples collected between 2003 and 2020 from 10 sites across England were typed with microsatellite markers. The analysis of 8 microsatellites indicated a clear east-west divide between N. ribisnigri populations, which corresponds with current outdoor lettuce cultivation distribution in England, one of the aphid's summer hosts. Analysis of gene flow indicated that aphids did not leave the eastern region; instead, there was strong evidence for aphids migrating from the West into the secondary host eastern region, possibly from the winter host (Ribes spp.) in Spring. This result suggests that although N. ribisnigri has the potential for long-distance migration, strong ties to the summer host (lettuce) determine migratory behavior at the population level. N. ribisnigri are mostly holocyclic and show a high level of inbreeding. Long-term trends revealed relatively stable populations, despite a recent breakdown of host plant resistance and other environmental changes, including favorable temperatures. The geographic and temporal structure of the N. ribisnigri population is discussed in relation to future pest management strategies.

Journal of Insect Science October 2025

Foliimonas ilicis gen. nov., sp. nov., a carbon monoxide-oxidizing bacterium belonging to a novel genus of the family Phyllobacteriaceae isolated from leaves of Ilex aquifolium

Sinchan Banerjee, Andras Tancsics, Zegin Wu, Tudor Stafioiu, Jiacheng Gao, Erika Toth, Erzsebet Baka, Garry Bending, Hendrik Schaefer

A novel carbon monoxide (CO)-oxidizing bacterial strain designated as SB112T was enriched and isolated from leaves from Tocil Wood Nature Reserve in Coventry, UK. The strain was Gram reaction-negative, aerobic, rod-shaped, motile with a polar flagellum and non-spore-forming. Growth of strain SB112T was observed at 10–45 °C, pH 6.0–12.0 and NaCl concentrations of 1–3%. The genomic DNA G+C content was 58.3 mol%, and the major fatty acids (>10%) of strain SB112T were C ω7c, C ω7c 11-methyl and C cyclo ω7c. Major polar lipids were phosphatidylcholine, diphosphatidylglycerol, phosphatidylglycerol and a phospholipid. Strain SB112ᵀ contains ubiquinone-10 as the major respiratory quinone. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain SB112T formed a separate lineage within the family , showing sequence identities of 97.7%, 97.6% and 97.5%, with its closest relatives , and , respectively. Phylogenomic analyses using whole-genome sequences consistently placed this strain within the family . However, its phylogenetic position did not correspond to any known genus within this family. The genome of strain SB112T was found to possess the form II gene, which encodes the large subunit of the CO dehydrogenase and potentially enables CO oxidation. The average nucleotide identity and digital DNA–DNA hybridization with members of closely related genera yielded values below the thresholds for prokaryotic species delineation (95–96 and 70%, respectively). Based on the phenotypic, chemotaxonomic, phylogenetic, genomic and physiological properties, strain SB112T is considered to represent a novel species of a new genus within the family for which the name gen. nov., sp. nov. is proposed. The type of strain is SB112T (=LMG 33802T, =NCAIM B.02691T

Microbiology Society

Mitochondrial ROS trigger interorganellular signaling and prime ER processes to establish enhanced plant immunity

Yang Yang, Yan Zhao, Wei Zhao, Yingqi Zhang, Hongmei Wang, Murray Grant, Patrick Schäfer, Yuling Meng, Weixing Shan

Reactive oxygen species (ROS) are key signaling molecules in plant development and immunity, but current understanding is primarily focused on apoplastic and chloroplastic ROS. Mitochondria are also a key source of intracellular ROS, yet their contribution to plant immunity is poorly characterized. Here, we studied mitochondrial ROS (mROS) function in plant-pathogen interactions, deploying genetically encoded sensors, assorted fluorescent markers, and genetic approaches to track mROS, specifically H2O2, dynamics and identify interorganelle contact sites. We unexpectedly found a mitochondria–endoplasmic reticulum (ER) ROS signal cascade functioning independently of apoplastic and chloroplastic ROS in plant immunity. mROS initiate immune responses induced by the oomycete pathogen Phytophthora parasitica and promote mitochondria-ER association. These enhanced mitochondria-ER membrane associations are required for transfer of mROS signals and initiation of extensive unfolded protein responses. We conclude that mROS transfer via mitochondria-ER membranes to the ER lumen is an underappreciated yet essential component in plant defense.

Science Advances 2025

Probing the mechanism of peptidoglycan amidase activation by FtsEX-EnvC

Cook Jonathan, Crow Allister

The FtsEX-EnvC-AmiA/B system is a key component of the E. coli cell division machinery that directs breakage of the peptidoglycan layer during separation of daughter cells. Structural and mechanistic studies have shown that ATP binding by FtsEX in the cytoplasm drives periplasmic conformational changes in EnvC, which lead to the binding and activation of peptidoglycan amidases such as AmiA and AmiB. The FtsEX-EnvC amidase system is highly regulated to prevent cell lysis with at least two separate layers of autoinhibition that must be relieved to initiate peptidoglycan hydrolysis during division. Here, we test the FtsEX-EnvC amidase activation mechanism through site-directed mutagenesis. We identify mutations that disrupt the autoinhibition mechanism of FtsEX-EnvC and an N-terminal deletion variant that prevents activation. Finally, we develop a cysteine locking residue pair that stabilizes the complex in its amidase activating conformation. The reported EnvC variants greatly enhance our understanding of the FtsEX-EnvC autoinhibition mechanism and the conformational changes underpinning amidase activation. Our observations are consistent with the proposed mechanism of amidase activation by large-scale conformational changes in FtsEX-EnvC, allowing recruitment and activation of peptidoglycan amidases.

MBIO-ASM Journals

Impact of seasonal climate variability on constructed wetland treatment efficiency

Dykes, Charlotte, Pearson, Jonathan M., Bending, Gary D. and Abolfathi, Soroush

Free-water surface constructed wetlands (CWs) are sustainable, low emission, nature-based solutions for water and wastewater treatment. However, the discharge of nutrient-rich effluents from CWs treating wastewater can adversely impact freshwater ecosystems and exacerbate eutrophication. Despite their ecological benefits, limited research exists on the treatment efficiency and pollutant dynamics of CWs under varying seasonal and environmental pressures. This study investigates the treatment efficiency of an integrated CW (ICW) serving as a nature-based solution for treating partially treated wastewater before release into the environment. Our findings highlight the dynamic and sensitive mechanisms influencing nutrient removal in CWs, driven by seasonal hydraulic conditions, vegetation phenology, and climatic factors. The study provides critical insights for optimizing CW design and management under fluctuating environmental conditions to enhance their resilience, ensure regulatory compliance, and maintain long-term treatment efficiency. This understanding is essential for guiding future regulatory policies and ensuring that CWs meet water quality standards in response to climate pressures.

Journal of Water Process Engineering. March 2025

Rootrainertrons: a novel root phenotyping method used to identify genotypic variation in lettuce rooting

Cara Wharton, Andrew Beacham, Miriam L. Gifford and James Monaghan

There is much interest in how roots can be manipulated to improve crop performance in a changing climate, yet root research is made difficult by the challenges of visualising the root system accurately, particularly when grown in natural environments such as soil. This study reports a novel, low cost, Rootrainer-based system for root phenotyping. This novel Rootrainertron method has many advantages over existing methods of phenotyping seedling roots. Rootrainers are cheap, and readily available from garden centres, unlike rhizotrons which are expensive and only available from specialist suppliers. Rootrainers allow the roots to grow in substrate medium, providing a significant advantage over agar and paper assays.This approach offers an affordable and relevant root phenotyping option and makes root phenotyping more accessible and applicable for researchers.

Plant Methods. March 2025

Cost-effectiveness of routine COVID-19 adult vaccination programmes in England

Matt J. Keeling, Edward M. Hill, Stavros Petrou, Phuong Bich Tran, May Ee Png, Sophie Staniszewska, Corinna Clark, Katie Hassel, Julia Stowe, Nick Andrews

In England, and many other countries, immunity to SARS-CoV-2 infection and COVID-19 disease is highly heterogeneous.. During the height of the pandemic in England, the main aim was to rapidly protect the population and large supplies of vaccine were pre-purchased, eliminating the need for cost-effective calculations. As we move to an era where for the majority of the population SARS-CoV-2 infections cause relatively mild disease, and vaccine stocks need to be re-purchased, it is important we consider the cost-effectiveness and economic value of COVID-19 vaccination programmes. Here using data from 2023 and 2024 in England on COVID-19 hospital admissions, ICU admissions and deaths, coupled with bespoke health economic costs, we consider the willingness to pay threshold for COVID-19 vaccines in different age and risk groups.

Vaccine. March 2025

One-two punch : phage-antibiotic synergy observed against staphylococcus aureus by combining pleurotin and phage K

Michaël Dagne Tadesse, Nala Ali, Martha White, Lijiang Song, Fabrizio Alberti, Antonia P. Sagona 

There is an urgent need for novel antimicrobial therapies, chemical and nonantibiotic. The basidiomycota-derived, secondary metabolite pleurotin has been shown to be effective against Gram-positive bacteria, while bacteriophages could be the ultimate nonantibiotic alternative. In this study, the combination of pleurotin and phage K targeting S. aureus was examined. Pleurotin was isolated from the basidiomycota fungus Hohenbuehelia grisea. The cytotoxicity of pleurotin was assessed in two human cell lines in comparison to pleuromutilin, vancomycin, and phage K. The antibiotics were then tested independently or in combination with phage K against two S. aureus strains. Cytotoxicity of pleurotin in human cells was comparable to vancomycin and pleuromutilin. Results suggest that adding phage K has a synergistic effect and can lower the MIC for pleurotin, pleuromutilin, and vancomycin. This demonstrates that pleurotin could be a viable antistaphylococcal drug.

ACS Omega. March 2025

Impact of Phage Therapy on Pseudomonas syringae pv. syringae and Plant Microbiome Dynamics Through Coevolution and Field Experiments

Matevz Papp-Rupar, Emily R. Grace, Naina Korotania, Maria-Laura Ciusa, Robert W. Jackson, Mojgan Rabiey

Isolation of phages targeting the cherry pathogen Pseudomonas syringae pv. syringae (Pss) led to five distinct phage genotypes. Building on previous in vitro coevolution experiments, the coevolution of the five phages (individually and as a cocktail) with Pss on cherry leaves was conducted in glasshouse and field experiments. Phages effectively reduced Pss numbers on detached leaves, with no evidence of phage resistance emerging in the bacterial population. Field application of phages in a cherry orchard in Southeast England evaluated phage survival, viability and impact on bacterial populations and the microbial community. The bacterial population and phages persisted in the leaf and shoot environment as long as the bacterial host was present. In contrast to in vitro studies, the plant environment constrained the emergence of phage resistant Pss populations.

Environmental Microbiology. March 2025

Single-calibration cell size measurement with flow cytometry

Philip Davies, Massimo Cavallaro, Daniel Hebenstreit

Measuring the size of individual cells in high-throughput experiments is often important in biomedical research and applications.  In this paper, we demonstrate that it is possible to calibrate flowcytometry laser scatter signals with accurate measures of cell diameter from separate devices and that the calibration can be conserved upon changes in the laser settings A straightforward procedure is presented that relates the flow cytometric scatter parameters to the absolute size measurements using linear models, along with a linear transformation that converts between different instrument settings on the flow cytometer. Our method makes it possible to record on a flow cytometer a cell's size in absolute units and correlate it with other features that are recorded in parallel in the fluorescence detection channels.

Cytometry Part A March 2025

Leishmaniasis in deployed military populations : a systematic review and meta-analysis

Niba Rawlings, Ngwa, Bailey, Mark and Courtenay, Orin

This systematic review and meta-analysis of data specific to military populations aims to identify knowledge gaps to mitigate sand fly exposure and Leishmania transmission during deployments. Regular use of long-lasting insecticidal nets to mitigate sand fly exposure demonstrated high potential effectiveness than other reported personal protective measures (PPMs) which yielded mixed or inconclusive results. In summary, the systematic review revealed the substantial variability between study designs and statistical integrity. There is need for more consistent and robustly designed studies including well-define controls and replication. Future studies would be advised to explore the long-term effectiveness and practicality of PPMs, both individually and in combination, across diverse deployment settings.

PLoS Neglected Tropical Diseases. March 2025

Historic manioc genomes illuminate traditional maintenance of diversity under long-lived clonal cultivation

Logan Kistler, Fabio de Oliveira Freitas, Rafal M. Gutaker, S. Yoshi Maezumi, Jazmín Ramos-Madrigal, Marcelo F. Simon, J. Moises Mendoza Flores, Sergei V. Drovetski, ¬Hope Loiselle, Eder Jorge de Oliveira, Eduardo Alano Vieira, Luiz Joaquim Castelo Branco Carvalho, Marina Ellis Perez, Audrey T. Lin, Hsiao-Lei Liu, Rachel Miller, Natalia A. S. Przelomska, Aakrosh Ratan, Nathan Wales, Kevin Wann, Shuya Zhang, Magdalena García, Daniela Valenzuela, Francisco Rothhammer, Calogero M. Santoro, Alejandra I. Domic, José M. Capriles, Robin Allaby

Manioc—also called cassava and yuca—is among the world’s most important crops, originating in South America in the early Holocene. Domestication for its starchy roots involved a near-total shift from sexual to clonal propagation, and almost all manioc worldwide is now grown from stem cuttings. In this work, we analyze 573 new and published genomes, focusing on traditional varieties from the Americas and wild relatives from herbaria, to reveal the effects of this shift to clonality. We observe kinship over large distances, maintenance of high genetic diversity, intergenerational heterozygosity enrichment, and genomic mosaics of identity-by-descent haploblocks that connect all manioc worldwide. Interviews with Indigenous traditional farmers in the Brazilian Cerrado illuminate how traditional management strategies for sustaining, diversifying, and sharing the gene pool have shaped manioc diversity.

Science. March 2025

Press release

Genetic and Pharmacological Inhibition of Metabotropic Glutamate Receptor Signalling Extends Lifespan in Drosophila

Cui Guan, Abigail Otchere, Mihails Laskovs, Irene Papatheodorou, Cathy Slack

Invertebrate models have been instrumental in advancing our understanding of the molecular mechanisms of ageing. The isolation of single gene mutations that both extend lifespan and improve age-related health have identified potential targets for therapeutic intervention to alleviate age-related morbidity. Here, we find that genetic loss of function of the G protein-coupled metabotropic glutamate receptor (DmGluRA) in Drosophila extends the lifespan of female flies. This longevity phenotype was accompanied by lower basal levels of oxidative stress and improved stress tolerance, and differences in early-life behavioural markers. Gene expression changes in DmGluRA mutants identified reduced ribosome biogenesis, a hallmark of longevity, as a key process altered in these animals. We further show that the pro-longevity effects of reduced DmGluRA signalling are dependent on the fly homologue of Fragile X Mental Retardation Protein (FMRP), an important regulator of ribosomal protein translation. Importantly, we can recapitulate lifespan extension using a specific pharmacological inhibitor of mGluR activity. Hence, our study identifies metabotropic glutamate receptors as potential targets for age-related therapeutics.

Aging Cell. February 2025

Quantifying integrated pest management adoption in food horticulture

Jennifer Byrne, Robert Lillywhite, Henry Creissen, Fiona Thorne, Lael Walsh

Integrated Pest Management (IPM) is a crop health paradigm offering a framework for sustainable pest management. To optimise adoption it is necessary to understand how growers use IPM, to identify measures lagging in uptake or suitability for uptake and to explore limitations to both. This study has quantified IPM adoption using Irish food horticulture as a case study, through the development and application of an IPM metric based on field, protected and top fruit production systems. While our results demonstrated that IPM has been adopted, it also suggested that there is room for improvement. This presentation of an IPM measurement instrument for temperate horticulture systems provides the means to benchmark IPM performance and chart cumulative progress. This is useful to policy makers and IPM stakeholders to compare performance on a national and cross-national basis with a view to refining best practice, while defining specific components of IPM for improvement.

Crop Protection. February 2025

Stephen Parnell Publications

Assessing delimiting strategies to identify the infested zones of quarantine plant pests and diseases

Koh, Joshua, Cunnifee, Nik and Parnell, Stephen

Following the discovery of a quarantine plant pest or disease, delimitation is urgently conducted to define the boundaries of the infested area, typically through surveys that detect the presence or absence of the pest. Swift and accurate delimitation is crucial after a pest or pathogen enters a new region for containment or eradication. In this study, we used an individual-based model to simulate the spread of Huanglongbing (citrus greening), a priority EU pest, and evaluated three delimiting strategies across various host distribution landscapes. We found that an adaptive strategy was most effective, especially when tailored to the polycyclic nature of the pest. This underscored the need for specific delimiting approaches based on the epidemiological characteristics of the target pest.

Scientific Reports. February 2025


Developing epidemiological preparedness for a plant disease invasion: Modelling citrus huánglóngbìng in the European Union

John Ellis, Elena Lázaro, Beatriz Duarte, Tomás Magalhães, Amílcar Duarte, Jacinto Benhadi-Marín, José Alberto Pereira, Antonio Vicent, Stephen Parnell, Nik J. Cunniffe

Huánglóngbìng (HLB) is a bacterial disease of citrus that has significantly impacted Brazil and the United States, although citrus production in the Mediterranean Basin remains unaffected. By developing a mathematical model of spread in Spain, we tested surveillance and control strategies before any future HLB entry in the EU. We found while some citrus production might be maintained by roguing, this requires extensive surveillance and significant chemical control, perhaps also including testing of psyllids (which spread the pathogen) for bacterial DNA. Our work highlights the key importance of early detection (including asymptomatic infection) and vector control for HLB management.

Plants, People, Planet. February 2025

Controlling endemic foot-and-mouth disease: Vaccination is more important than movement bans. A simulation study in the Republic of Turkey

Glen Guyver-Fletcher, Erin E. Gorsich, Chris Jewell, Michael J. Tildesley

In this article we present a spatially-explicit stochastic metapopulation model to simulate the spread and control of foot-and-mouth disease (FMD) in an endemic setting. We parameterise and validate the model using detailed outbreak data from the Republic of Turkey, 2001–2012. Subsequently, we assess the efficacy of ring vaccination, mass vaccination, and livestock movement restrictions with regards to incidence-reduction and likelihood of eradication. Our results suggest countries wishing to control the disease within their borders should focus on comprehensive surveillance and vaccination campaigns as their main policy goals. In summary, vaccination-based policies are more effective than movement restrictions in the endemic context.

Infectious Disease Modelling.; February 2025

Knockout of fatty acid elongase1 homeoalleles in amphidiploid Brassica juncea leads to undetectable erucic acid in seed oil

Nelesh Patra , Guy C. Barker , Mrinal K. Maiti

Indian mustard (Brassica juncea L.) seed oil offers valuable dietary benefits due to a balanced ratio of human essential fatty acids, the traditional high oil-yielding varieties contain an elevated level of erucic acid (EA, C22:1) associated with adverse health effects. Therefore, developing low erucic acid (LEA) mustard cultivars is crucial for broader utilization and consumer safety. In this study, CRISPR/Cas9 genome editing tool was employed to disrupt the fatty acid elongase1 (FAE1) gene that encodes a key enzyme in EA biosynthesis in two high erucic acid (HEA) B. juncea cultivars, PCR7 (∼39% EA) and JD6 (∼45% EA). Our findings underscore the effectiveness of CRISPR/Cas9 technology for editing B. juncea genome, developing plant lines producing LEA seed oil with improved nutritional quality and broadening the utility of this important oilseed crop for food and non-food applications.

Plant Physiology & Biochemistry. February 2025

Phylodynamic analysis of a prolonged meningococcal epidemic reveals multiple introductions and pre-epidemic expansion

Zuyu Yang, Heather Davies, Jane Clapham, Liza Lopez, Holly B Bratcher, Audrey Tong, Xavier Didelot, Martin C.J. Maiden, Philip E. Carter, Xiaoyun Ren

Neisseria meningitidis is the causative agent of invasive meningococcal disease (IMD), a form of bacterial meningitis and septicaemia, leading to isolated cases, outbreaks, and epidemics worldwide. Between 1991 and 2008, Aotearoa/New Zealand (NZ) experienced a prolonged hyperendemic group B IMD outbreak caused by the NZMenB epidemic strain. To understand NZMenB origin and initiation we used phylodynamic tools to analyse approximately 97 % of all NZMenB isolates submitted to the NZ Meningococcal Reference Laboratory from 1990 to 2019.. Our evidence from molecular dating and clonal expansion analysis suggests that NZMenB was circulating and had expanded before the epidemic. Comparison with international data showed multiple importations and re-introductions of NZMenB into NZ, while not suggesting close relationships with international variants. We propose the NZMenB epidemic may have been triggered by increasing societal inequality and household crowding resulting from government policies at the time.

Infection, Genetics and Evolution. February 2025

Piperideine-6-carboxylic acid regulates vitamin B6 homeostasis and modulates systemic immunity in plants

Huazhen Liu, Lakshminarayan M. Iyer, Paul Norris, Ruiying Liu, Keshun Yu, Murray Grant, L. Aravind, Aardra Kachroo & Pradeep Kachroo

Dietary consumption of lysine in humans leads to the biosynthesis of Δ1-piperideine-6-carboxylic acid (P6C), with elevated levels linked to the neurological disorder epilepsy. Here we demonstrate that P6C biosynthesis is also a critical component of lysine catabolism in Arabidopsis thaliana. P6C regulates vitamin B6 homeostasis, and increased P6C levels deplete B6 vitamers, resulting in compromised plant immunity. We further establish a key role for pyridoxal and pyridoxal-5-phosphate biosynthesis in plant immunity. Our analysis indicates that P6C metabolism probably evolved through combining select lysine and proline metabolic enzymes horizontally acquired from diverse bacterial sources at different points during evolution. More generally, certain enzymes from the lysine and proline metabolic pathways were probably recruited in evolution as potential guardians of B6 vitamers and for semialdehyde detoxification.

Nature Plants. February 2025

International Consortium to Classify Ageing related Pathologies (ICCARP) senescence defnitions: achieving international consensus

Emma Short, Robert T.R. Huckstepp et al

It is paramount that the language used in the scienitifc and medical literature is clear and unambiguous to ensure shared understanding amongst researchers, clinicians, and policymakers. The aim of the ICCARP is to develop a systematic and comprehensive classifcation system for ageingrelated changes including pathologies, diseases, and syndromes. Currently, the ICCARP is in the process of identifying all phenomena that meet the criteria for ageing-related pathologies, to develop proposals for grouping and naming them within a comprehensive classification system. We expect that these defnitions, and subsequent classifcations, will contribute to improving discourse, research methodologies, clinical diagnostics, and public health planning.

Geroscience. February 2025

Quantifying infectious disease epidemic risks: A practical approach for seasonal pathogens

Alexander R Kaye, Giorgio Guzzetta, Michael J Tildesley

For many infectious diseases, the risk of outbreaks varies seasonally. If a pathogen is usually absent from a host population, a key public health policy question is whether the pathogen’s arrival will initiate local transmission, which depends on the season in which arrival occurs. This question can be addressed by estimating the “probability of a major outbreak” (the probability that introduced cases will initiate sustained local transmission). We have devised an approach for inferring outbreak risks for seasonal pathogens (involving calculating the Threshold Epidemic Risk; TER). Estimation of the TER involves calculating the probability that introduced cases will initiate a local outbreak in which a threshold number of cumulative infections is exceeded before outbreak extinction. For simple seasonal epidemic models, such as the stochastic Susceptible-Infectious-Removed model, the TER can be calculated numerically (without model simulations). For more complex models, such as stochastic host-vector models, the TER can be estimated using model simulations.

PLoS Computational Biology. February 2024

Phospho-tau serine-262 and serine-356 as biomarkers of pre-tangle soluble tau assemblies in Alzheimer’s disease

Tohidul Islam et al, including Emily Hill & Mark J Wall

Patients with Alzheimer’s disease (AD) with little or no quantifiable insoluble brain tau neurofibrillary tangle (NFT) pathology demonstrate stronger clinical benefits of therapies than those with advanced NFTs. The formation of NFTs can be prevented by targeting the intermediate soluble tau assemblies (STAs). However, biochemical understanding and biomarkers of STAs are lacking. Our findings inform about the status of early-stage tau aggregation, reveal aggregation-relevant phosphorylation epitopes in tau and offer a diagnostic biomarker and targeted therapeutic opportunities for AD.

Nature Medicine. February 2025 

Press Release

Multiple carbamylation events are required for differential modulation of Cx26 hemichannels and gap junctions by CO2

Sarbjit Nijjar, Deborah Brotherton, Jack Butler, Valentin-Mihai Dospinescu, Harry G Gannon, Victoria Linthwaite, Martin Cann, Alexander Cameron, Nicholas Dale 

CO2 directly modifies the gating of connexin26 (Cx26) gap junction channels and hemichannels. This gating depends upon Lys125, and the proposed mechanism involves carbamylation of Lys125 to allow formation of a salt bridge with Arg104 on the neighbouring subunit. We demonstrate via carbamate trapping and tandem mass spectrometry that five Lys residues within the cytoplasmic loop, including Lys125, are indeed carbamylated by CO2 . Our findings directly demonstrate carbamylation in connexins, provide further insight into the differential action of CO2 on Cx26 hemichannels and gap junction channels, and increase support for the role of the N-terminus in gating the Cx26 channel. KEY POINTS: Direct evidence of carbamylation of multiple lysine residues in the cytoplasmic loop of Cx26. Concentration-dependent carbamylation at lysines 108, 122 and 125. Only carbamylation of lysine 125 is essential for hemichannel opening to CO2. Carbamylation of lysine 108 along with lysine 125 is essential for CO2-dependent gap junction channel closure.

Journal of Physiology. February 2025

Antimicrobial triazinedione inhibitors of the translocase MraY–protein E interaction site: synergistic effects with bacitracin imply a new mechanism of action

Julia A. Fairbairn, Rachel V. Kerr, Nika-Kare A. Pierre-White, Anthony Jacovides, Becca W. A. Baileeves, Phillip J. Stansfeld, Gerhard Bringmann, Andrew T. Merritt and Timothy D. H. Bugg

Escherichia coli translocase MraY is the target for bacteriolytic protein E from bacteriophage fX174, interacting at a site close to Phe-288 on helix 9, on the extracellular face of the protein. A peptide motif Arg-Trp-x-x-Trp from protein E was used to design a set of triazinedione peptidomimetics, which inhibit particulate MraY (6d IC50 48 µM), and show antimicrobial activity against Gram-negative and Gram-positive antibiotic-resistant clinical strains (7j MIC Acinetobacter baumannii 16 µg/mL, Staphyloccoccus aureus MRSA 2-4 µg/mL). Docking against a predicted structure for E. coli MraY revealed two possible binding sites close to helix 9, the binding site for protein E. Antimicrobial activity of analogue 6j was found to be synergistic with bacitracin in Micrococcus flavus, consistent with a link between this inhibition site and undecaprenyl phosphate uptake. Alkaloid michellamine B, also predicted to bind in the cleft adjacent to helix 9, was also found to be synergistic with bacitracin. These data provide experimental evidence that the unusual hydrophobic cleft adjacent to helix 9 in MraY is involved in uptake of undecaprenyl phosphate, in addition to recently identified transporters UptA and PopT, and that this process can be targetted by small molecules as a novel antibacterial mechanism.

RSC Medicinal Chemistry. January 2025

A comparative study of ionic pesticide sorption and degradation in contrasting Brazilian soils and the development of a novel 3-Phase Assay to assess sorption reversibility

Baudin, Nastasia, Garrod, Mark, Bramke, Irene, Mckillican, Carol, Schafer, Hendrik, Hand, Laurence, Cione, Ana, Bending, Gary D, Marshall, Samantha

Brazilian soils have distinctive characteristics to European and North American soils which are typically used to investigate pesticide fate. This study aimed to compare soil–water partition coefficient (Kd), reversibility of adsorption and degradation half-life (DT50) of 5 pesticides covering a wide range of physico-chemical properties in contrasting Brazilian soils and a temperate (UK) alfisol soil, and to study their relationship with soil OM, clay and expandable clay content, CEC and pH. The results showed that pesticide behaviour in Brazilian soils was not systematically different from those in European and North American soils. The 3PA was shown to be a reliable and simple method for assessing pesticide desorption in soil and could be adapted to assess pesticide bioavailability. The use of the 3PA allowed a more thorough explanation of the observed differences in degradation behaviour between the compounds.

Environmental Monitoring and Assessment. January 2025

MCC950 Mitigates SIRT3-NLRP3-driven Inflammation and Rescues Post-Stroke Neurogenesis

Prakash R., Waseem A., Siddiqui A.J., Naim M., Khan M.A., Robertson A.A.B., Boltze J., Raza S.S.

after ischemic stroke. The objective of this study was to examine the potential mechanism by which the SIRT3-NLRP3 inflammasome affects neural stem and progenitor cells (NSPCs) after transient middle cerebral artery occlusion (tMCAO) in rats. Overall, our results suggest that protecting NSPCs and neurogenesis in the ischemically damaged brain by mitigating the impact of the SIRT3-NLRP3 inflammasome may be a feasible treatment strategy for ischemic stroke.

Biomedicine and Pharmacotherapy. January 2025

Inference of multiple mergers while dating a pathogen phylogeny

Helekal, David, Koskela, Jere and Didelot, Xavier

Here we consider the problem of detecting the presence of multiple mergers in the context of dating a phylogeny, that is determining the date of each of the nodes. We use the Lambda-coalescent theory as a modelling framework and show how Bayesian inference can be efficiently performed using a Billera-Holmes- Vogtmann space embedding and a customised Markov Chain Monte Carlo sampling scheme. We applied this new analysis methodology to a large number of simulated datasets to show that it is possible to infer if and when multiple merger events occurred, and that the phylogenetic dating is improved as a result of taking this information into account. We also analysed real datasets of Vibrio cholerae and Mycobacterium tuberculosis to demonstrate the relevance of our approach to real pathogen evolutionary epidemiology. We have implemented our new methodology in a R package which is freely available at https://github.com/dhelekal/MMCTime.

Systematic Biology. January 2025

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