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An Interdisciplinary Research Centre at the University of Cambridge
 

Microbial quorum sensing signals, symbiosis, secrets and sabotage

Recent Publications - Wed, 29/07/2026 - 11:00

Microbiology (Reading). 2026 Jul;172(7). doi: 10.1099/mic.0.001752.

ABSTRACT

Bacteria exhibit sophisticated forms of multicellularity by coordinating the activities of individual cells with respect to behaviours such as symbiosis, conjugation, competence, swarming, secondary metabolite production, biofilm formation, growth inhibition, niche adaptation and virulence. Apart from direct cell-cell contact, the synthesis, release and perception of small diffusible chemicals acting as inter-cellular signals offer the most obvious mechanism for bacterial cell populations to synchronize their behaviour. Such cell-cell communication (quorum sensing) offers a unique framework for understanding how bacteria convert chemical information into coordinated group behaviours. It is deeply influenced by ecology, host interactions, chemical diversity and spatial architecture. Despite much progress, many fundamental questions remain unresolved, especially in natural, polymicrobial and host-associated environments. Here, we summarize our current understanding of bacterial cell-cell communication and main knowledge gaps and highlight examples of translational opportunities.

PMID:42524873 | DOI:10.1099/mic.0.001752

How understanding the diversity of perspectives and systems in governments can increase the impact of scientific research

Recent Publications - Fri, 24/07/2026 - 11:00

Commun Health. 2026;1(1):13. doi: 10.1038/s44528-026-00009-2. Epub 2026 Jul 22.

ABSTRACT

The COVID-19 crisis required scientists worldwide to contribute to complex, hectic, and unfamiliar governmental decision-processes. In this Perspective, we reflect on this intense interaction between science and health policy for pandemic response, drawing from the experience of infectious disease modellers across the world. We highlight the diversity of actors and interests in government, aiming to demystify the elusive 'policy makers'. We present a general taxonomy to help research scientists more effectively support evidence-based policy. We stress the importance of building and maintaining relationships appropriate to the diverse pool of government actors. Not recognising this diversity may lead to miscommunication and reduce the positive impacts of scientific evidence for public policy in crisis and non-crisis situations.

PMID:42494828 | PMC:PMC13391366 | DOI:10.1038/s44528-026-00009-2

AllTheBacteria: a community resource empowers biology and discovers novel peptide antibiotics

Recent Publications - Fri, 17/07/2026 - 11:00

bioRxiv [Preprint]. 2026 Jul 7:2024.03.08.584059. doi: 10.1101/2024.03.08.584059.

ABSTRACT

Public microbial genomes encode an immense record of biological diversity, evolution and molecular function, but much of this information remains difficult to reuse because raw sequencing data are not uniformly assembled, quality controlled, annotated or searchable at scale. Here we present AllTheBacteria, an open, community-built resource that transforms public bacterial short-read whole-genome sequencing reads into a uniformly processed discovery platform. The current analysed release contains 2,440,377 high-quality bacterial and archaeal genomes from 11,273 species, together with standardized taxonomic assignments, genome annotations, antimicrobial resistance calls, antiphage-defence annotations, protein structure predictions and AI-ready sequence tables. We show that this infrastructure enables applications that would otherwise be impractical, from global sequence search and outbreak contextualization to pangenome method development, antimicrobial resistance reservoir mapping and antiphage-defence ecology. As a stringent experimental demonstration, we mined 3,919,096 encrypted peptide fragments from AllTheBacteria proteomes using our deep learning model APEX 1.1, identifying 1,867 candidates with predicted antimicrobial activity. We synthesized 24 representative peptides and tested them against 20 clinically relevant bacterial strains, including antibiotic-resistant pathogens. Multiple peptides showed low-micromolar activity, membrane-responsive conformational transitions and selective envelope perturbation. A lead molecule, ATB20, reduced Acinetobacter baumannii burden in a murine skin abscess model with efficacy comparable to polymyxin B and no overt toxicity. Together, these results establish AllTheBacteria as both a foundational community resource for microbiology and a renewable engine for AI-guided antimicrobial discovery.

PMID:42465405 | PMC:PMC13370402 | DOI:10.1101/2024.03.08.584059

Patching up the nucleus: a novel role for PMLII in nuclear envelope stability

Recent Publications - Thu, 16/07/2026 - 11:00

Nucleic Acids Res. 2026 Jul 3;54(13):gkag665. doi: 10.1093/nar/gkag665.

ABSTRACT

The nuclear envelope (NE) is important for cellular health as it protects and organizes the genome. NE dynamics are important for various cellular processes, including cell growth, migration, and removal of defective NE components. In extreme cases, the NE can rupture, followed by rapid repair to minimize damage to the genome. While our understanding of the repair process is increasing, a lot is still unknown about events leading up to NE rupture. Here, we found that promyelocytic leukemia protein isoform II (PMLII), a protein involved in nuclear PML body formation, forms condensates at the NE. PML condensates specifically form at sites where the lamina is disrupted, and two predicted amphipathic α-helices in the unique C-terminus of PMLII are essential for this localization. Live-cell imaging showed that when NE rupture occurs at these sites, the PMLII patch remains present until rupture repair is initiated. Using stable cell lines expressing FLAG-PMLII in a PML knockdown background, we found that PMLII caused an increase in the size of lamin holes without increasing the number of NE ruptures. We therefore hypothesize that PML patches play a role in NE integrity maintenance and dynamics through the stabilization of large holes in the lamina.

PMID:42463283 | DOI:10.1093/nar/gkag665

Successful bioassay of blood from chronic wasting disease-affected cervids in cervid PrP transgenic Drosophila

Recent Publications - Thu, 16/07/2026 - 11:00

Acta Neuropathol Commun. 2026 Jul 15. doi: 10.1186/s40478-026-02372-1. Online ahead of print.

ABSTRACT

Chronic wasting disease is a fatal transmissible prion condition of free-ranging and farmed cervids including deer, elk, moose, muntjac and reindeer. Prionemia is a pathogenic feature of chronic wasting disease in cervids and underpins development of an ante-mortem blood test for effective disease management. To help achieve this goal, we show here that cervid PrP transgenic Drosophila can detect prion-infected blood from cervids with chronic wasting disease. We first established that cervid PrP Drosophila were highly sensitive to cervid prions since these flies were responsive to dilutions in the range of 10- 2 to ≥ 10- 10 of brain homogenate from terminal chronic wasting disease-affected cervids. We subsequently showed cervid PrP Drosophila developed a neurotoxic phenotype, evidenced by accelerated loss of locomotor activity and survival, after exposure to blood from cervids with experimental or natural chronic wasting disease. Cervid PrP Drosophila were sensitive to whole blood and blood fractions including plasma, buffy coat and different leukocyte subsets isolated from prion disease-affected cervids. Importantly, we showed that cervid PrP Drosophila were sensitive to blood samples isolated from chronic wasting disease-affected cervids during the pre-clinical phase of the condition. Significantly, we demonstrated that the neurotoxic fly phenotype which developed after exposure to prion-infected cervid blood was transmissible but was not associated with the accumulation of RT-QuIC-detectable prion seeding activity, which does occur after exposure to brain-derived cervid prions. Our data show that cervid PrP Drosophila can successfully detect blood from CWD-affected cervids and indicate that blood-borne prions have distinct propagation properties in PrP transgenic Drosophila compared to brain-derived prions.

PMID:42458630 | DOI:10.1186/s40478-026-02372-1

<em>Helicobacter pylori</em>, herpes simplex virus-1, varicella-zoster virus, and dementia risk

Recent Publications - Mon, 13/07/2026 - 11:00

Alzheimers Dement (Amst). 2026 Jul 6;18(3):e70414. doi: 10.1002/dad2.70414. eCollection 2026 Jul-Sep.

ABSTRACT

INTRODUCTION: Helicobacter pylori (H. pylori), herpes simplex-1 (HSV-1), and varicella-zoster virus (VZV) could increase dementia risk; however, evidence from large cohorts with long-term follow-up is scarce.

METHODS: Multivariable-adjusted Cox proportional-hazards models were used to investigate the association between H. pylori, HSV-1, and VZV seropositivity and dementia risk over 24 years in 8550 participants from the European Prospective Investigation into Cancer in Norfolk study in the United Kingdom.

RESULTS: H. pylori (hazard ratio [HR] = 1.24, 95% confidence interval [CI]: 1.09 to 1.41), but not HSV-1 (HR = 1.03, 95% CI: 0.91 to 1.18) or VZV (HR = 1.01, 95% CI: 0.86 to 1.19), was associated with dementia risk. The H. pylori-dementia association remained robust among incident cases >15 years after blood draw (HR = 1.26, 95% CI: 1.06 to 1.48). Seropositive tertiles of the H. pylori antibodies CagA (p = 0.007) and GroEL (p = 0.001) demonstrated significant trends with dementia risk.

DISCUSSION: H. pylori may represent a novel dementia prevention target, although early-life socioeconomic factors might confound the association.

PMID:42441168 | PMC:PMC13336066 | DOI:10.1002/dad2.70414

Periodic shifts in viral load increase risk of Hendra virus spillover from <em>Pteropus</em> bats

Recent Publications - Fri, 10/07/2026 - 11:00

Sci Adv. 2026 Jul 10;12(28):eaea6654. doi: 10.1126/sciadv.aea6654. Epub 2026 Jul 10.

ABSTRACT

Prediction and management of zoonotic spillover requires an understanding of infection dynamics within reservoir host populations. Spillover risk is commonly inferred from infection prevalence based on detection of viral genomic material, yet detection alone does not indicate the presence of infectious virus or a sufficient dose for transmission. We undertook a comprehensive investigation of Hendra virus shedding in its primary reservoir, Pteropus bats, analyzing quantitative PCR with reverse transcription (RT-qPCR) data from 6151 pooled urine samples collected across five sites over 3 years. We assessed longitudinal associations between viral prevalence (proportion of positive pooled urine samples), viral load proxies, and equine spillover, using generalized additive models and a permutation analysis. Peak prevalence periods associated with spillover events (N = 5) had a higher proportion of samples with high viral loads than periods without spillover. Prolonged periods of low viral load and low prevalence likely reflect noninfectious RNA or doses insufficient for cross-species transmission. Incorporating viral load metrics alongside prevalence can improve prediction of spillover risk.

PMID:42430468 | DOI:10.1126/sciadv.aea6654

ABC-RF-rejection: A two-stage machine-learning-enhanced framework for efficient likelihood-free inference

Recent Publications - Wed, 08/07/2026 - 11:00

Epidemics. 2026 Jul 1;56:100931. doi: 10.1016/j.epidem.2026.100931. Online ahead of print.

ABSTRACT

Accurate parameter estimation is fundamental to quantitative epidemiology as it provides the foundation for robust modelling and evidence-based decision-making. We present a novel two-stage framework, that is designed to enhance computational efficiency for parameter estimation of complex, stochastic, or spatially explicit models. Traditional Approximate Bayesian Computation (ABC) methods often face prohibitive costs when likelihoods are analytically intractable and acceptance rates are low. Our hybrid approach, ABC-RF-rejection, integrates ABC rejection sampling with Random Forest (RF) classification to selectively identify parameter sets likely to satisfy observed data constraints. In the first stage, a small-scale ABC rejection step generates a labelled training dataset of accepted and rejected particles. In the second stage, a trained RF model decouples posterior exploration from expensive forward simulations by predicting acceptance probabilities for a substantially larger candidate set. This allows the algorithm to focus computational resources on high-probability regions of the parameter space. We apply the ABC-RF-rejection approach to three distinct epidemiological contexts: stochastic simulations of onchocerciasis vector control, spatially explicit modelling of cassava brown streak virus spread in Uganda, and the 2014-2015 West Africa Ebola outbreak in heterogeneous populations. This framework provides an adaptable and robust solution for rapid, evidence-based decision-making in settings characterised by spatial heterogeneity, stochasticity, and limited surveillance data.

PMID:42419005 | DOI:10.1016/j.epidem.2026.100931

A conserved VPS34-PIKfyve-TRPML1-myosin II axis regulates the speed of amoeboid cell migration

Recent Publications - Tue, 07/07/2026 - 11:00

EMBO Rep. 2026 Jul 7. doi: 10.1038/s44319-026-00861-x. Online ahead of print.

ABSTRACT

Amoeboid cell migration is key to efficient T cell immunity. Spatial polarization of organelles within cells, including endo-lysosomes, is a prerequisite of migration. However, how ultrastructural polarization is linked to the signaling requirements governing T cell migration remains unknown. Here we show that signaling molecules generated by endo-lysosome-localized kinases regulate velocity of amoeboid migration. Specifically, imaging of T cells identifies accumulation of endo-lysosomes decorated with the lipid kinases VPS34-PIKfyve at the uropod of polarized cells. Activity of VPS34 and PIKfyve regulates speed, but not directedness, of migrating T cells. Mechanistically, PI(3,5)P2 generated by the sequential action of VPS34 and PIKfyve, mediates Ca2+ efflux from lysosomes via the mucolipin TRP cation channel 1 (TRPML1), thus controlling activity of myosin IIA and hence the generation of propulsive force through retrograde actin flow. The VPS34-PIKfyve kinases also regulate velocity of myeloid cells, as well as of the amoeba Dictyostelium discoideum - establishing the axis as an evolutionarily conserved speed control system of amoeboid cell migration.

PMID:42414599 | DOI:10.1038/s44319-026-00861-x

The Vertebrate Genomes Project Phase I: A global reference genome resource

Recent Publications - Fri, 03/07/2026 - 11:00

bioRxiv [Preprint]. 2026 Jun 25:2026.06.24.732306. doi: 10.64898/2026.06.24.732306.

ABSTRACT

The Vertebrate Genomes Project (VGP) aims to produce complete and near-error-free reference genomes for all ~70,000 extant vertebrate species1. Organized in four phases, it progressively targets all vertebrate orders, families, genera, and eventually all species. Here we present the completion of VGP Phase I, delivering reference genomes for ~95% of vertebrate orders, along with additional lineages within those orders, totaling 816 species and 1.6 trillion base pairs of main haplotype sequence. These genomes were assembled and annotated over an 8-year period (2018-2026) of rapid advances in genome sequencing, assembly, and annotation methods2-4, alongside the growth of associated consortium initiatives and international collaborations5-9. They represent some of the highest-quality vertebrate genomes currently available, and most have become the primary reference for their respective species in public databases. Comparative analyses across a subset of 579 species when we reached a threshold of 85% of orders allowed us to reconstruct the genome of the last common ancestor of all vertebrates 500 million years ago, identify diverse modes of sex chromosome evolution, reveal clade-specific three-dimensional genome architecture, discover methylated epigenetic landscapes across vertebrates, and provide a framework for studying gene and pseudogene evolution, immune loci, cancer-associated genes, and other trait-associated loci. Approximately a quarter of this subset are listed as Vulnerable to Critically Endangered by the IUCN Red List of Threatened Species, and have enabled more advanced genomic investigations of extinction risk. VGP Phase I delivers a reference backbone for vertebrate genomics, enabling discoveries that would otherwise remain out of reach across evolution, conservation, and medicine.

PMID:42395566 | PMC:PMC13320880 | DOI:10.64898/2026.06.24.732306

Predicting the cross-continental spread of the cassava brown streak disease epidemic in sub-Saharan Africa

Recent Publications - Thu, 02/07/2026 - 11:00

Sci Rep. 2026 Jul 2. doi: 10.1038/s41598-026-59438-2. Online ahead of print.

ABSTRACT

Cassava brown streak disease (CBSD) is a major threat to smallholder farmers in sub-Saharan Africa (SSA), where cassava is a staple crop. Caused by cassava brown streak ipomoviruses (CBSIs), CBSD has spread extensively since its detection in Uganda in 2004, raising concerns about ongoing spread through Southern and Central Africa and potential expansion to West Africa, home to the world's largest cassava producer, Nigeria. Building on a stochastic epidemiological model that predicts CBSD spread at the scale of Uganda, we incorporate extensive field surveillance records to extend the model to all thirty-two major cassava-producing countries in SSA. We then deploy the model to address key strategic questions such as estimating the present day CBSD distribution and predicting rates of ongoing spread towards West Africa. We also evaluate the risk of direct introductions resulting from extreme cases of long-range movement of infected planting material by air, sea or land, which could trigger outbreaks far beyond normal dispersal limits. Our model predicts the likely arrival of CBSD in Nigeria via cross-continental spread within 25 years, and if directly introduced anywhere in West Africa, spreading to most West African nations within 10 years of introduction. The risks of ongoing and future CBSD spread highlighted in this study underscore the need for proactive phytosanitation measures, including clean seed programs, vector control, and quarantine policies to curb CBSD spread. Moreover, the model described in this study not only provides estimates for arrival times across SSA, but also lays the foundations for a continental-scale quantitative framework wherein both surveillance and management options can be explored and optimised.

PMID:42393109 | DOI:10.1038/s41598-026-59438-2

Mapping SARS-CoV-2 immunity after an XBB.1.5 booster by antigenic cartography of merged human and hamster sera

Recent Publications - Wed, 01/07/2026 - 11:00

NPJ Vaccines. 2026 Jul 2. doi: 10.1038/s41541-026-01516-7. Online ahead of print.

ABSTRACT

The ongoing evolution of SARS-CoV-2, particularly the emergence and rapid spread of new immune-evasive variants, continues to challenge the durability of vaccine-induced protection. Understanding how repeated variant exposures shape neutralizing antibody breadth is therefore essential for optimizing booster design. Here, we investigated polyclonal neutralizing antibody responses in individuals who received a bivalent (ancestral + BA.4/5) boost followed by an additional monovalent XBB.1.5 boost, with and without breakthrough infection, against a diverse panel of SARS-CoV-2 variants. To visualize human multi-exposure immunity in antigenic space via antibody landscapes, we extended our existing human sera-based antigenic map with hamster sera infected with more recent variants. The hamster sera allowed us to map BA.2.86 and JN.1 variants, which largely escape human single exposure sera. Our analysis of human multi-exposure sera revealed that the number and type of exposures significantly shaped antibody landscapes. The XBB.1.5 booster immunization notably increased neutralizing antibody titers across variants, elevating the height of the antibody landscape. However, titers against more recent Omicron variants, such as JN.1, were low despite booster administration. These findings highlight the dynamic nature of SARS-CoV-2 immunity and emphasize the need for continuous monitoring and adaptation of vaccine strategies to maintain effective protection against emerging variants.

PMID:42386782 | DOI:10.1038/s41541-026-01516-7

COVID-19 vaccination induces cross-neutralisation of sarbecoviruses related to SARS-CoV-2

Recent Publications - Wed, 01/07/2026 - 11:00

NPJ Vaccines. 2026 Jul 1;11(1):125. doi: 10.1038/s41541-026-01469-x.

ABSTRACT

The combined threats of future sarbecovirus zoonosis and continually emerging SARS-CoV-2 VOCs highlight the need to assess the breadth of existing SARS-CoV-2 vaccine-mediated protection. Here, we investigate a cohort of older individuals who received four COVID-19 vaccine doses, for potential cross-neutralisation against lentiviral particles bearing spikes from either Omicron VOCs or other sarbecoviruses. Despite recent fourth bivalent mRNA vaccine doses (encoding SARS-CoV-2 Wu-1 and Omicron spikes), neutralisation of Omicron lineage VOCs was reduced compared to Wu-1, consistent with an imprinted immune response. Similarly, particles bearing either SARS-CoV-1 or a SARS-CoV-1-related bat sarbecovirus spike were neutralised less efficiently than Wu-1. Unexpectedly, however, we observed that particles with spikes from two animal SARS-CoV-2-related viruses, BANAL-20-52 from bats and a pangolin CoV, were significantly more sensitive to serum neutralising antibodies than SARS-CoV-2 Wu-1 itself. These surprising findings suggest that vaccine-mediated adaptive immunity may provide efficient cross-neutralisation and potential protection against certain animal sarbecoviruses.

PMID:42386763 | DOI:10.1038/s41541-026-01469-x

A computational method to design broad-spectrum T cell-inducing vaccines applied to Betacoronaviruses

Recent Publications - Mon, 29/06/2026 - 11:00

Cell Rep Methods. 2026 Jun 29:101508. doi: 10.1016/j.crmeth.2026.101508. Online ahead of print.

ABSTRACT

Antigenically diverse pathogens such as coronaviruses pose substantial global health threats, highlighting the need for broad-spectrum vaccines. Here, we introduce Spectravax, a computational method that designs broad-spectrum vaccines accounting for genetic diversity in both host and pathogen populations. Using Spectravax, we designed a nucleocapsid (N) antigen to elicit cross-reactive immune responses to viruses from the Sarbecovirus and Merbecovirus subgenera of Betacoronaviruses. In silico analyses demonstrated superior predicted host and pathogen coverage for Spectravax compared to wild-type sequences and existing computational designs. Experimental validation in mice supported these predictions: Spectravax N elicited robust immune responses to SARS-CoV, SARS-CoV-2, and MERS-CoV-the three coronaviruses responsible for major outbreaks in humans since 2002-while wild-type and existing computational designs elicited limited responses. Furthermore, we identified the MERS-CoV N epitopes responsible for Spectravax's cross-reactivity, advancing the rational design of broad-spectrum vaccines for pandemic preparedness.

PMID:42372721 | DOI:10.1016/j.crmeth.2026.101508

Ensemble Machine Learning Approaches Predict Survival in Lower-Grade Glioma Based on Glycosphingolipid Gene Expression and Metabolic Modeling

Recent Publications - Mon, 29/06/2026 - 11:00

Comput Struct Biotechnol J. 2026 Jun 26;35(1):0143. doi: 10.34133/csbj.0143. eCollection 2026.

ABSTRACT

Glycosphingolipids (GSLs) are essential components of biological membranes with important roles in cell signaling. Disrupted GSL metabolism is associated with malignancy across a range of cancers, with different GSLs implicated in distinct tumors. GSLs have potential mechanistic roles in cancer; however, their functions in lower-grade gliomas (LGGs) remain poorly understood. We present ensemble machine learning approaches using transcriptomic data from LGG, combined with GSL-specific metabolic simulations, to predict survival outcomes. The ensemble approach demonstrates effective risk stratification for LGG patients based on GSL synthetic enzyme expression. Pathway analysis of model-derived risk groups identified correlations with GSL-modulated pathways including cell motility, division, and Wnt signaling in LGG pathology. Given the strong performance of machine learning approaches to predict survival outcomes and that GSLs are shed into the tumor microenvironment, GSL-based diagnostics and prognostics may prove to be clinically beneficial upon future experimental validation. A Python package enabling GSL-specific metabolic modeling and risk prediction from RNA sequencing data is provided.

PMID:42368494 | PMC:PMC13305194 | DOI:10.34133/csbj.0143

Multiomic analysis identifies glutaminolysis-dependent metabolic enhancement of immune memory utilised for vaccine development

Recent Publications - Fri, 26/06/2026 - 11:00

Nat Commun. 2026 Jun 26. doi: 10.1038/s41467-026-74866-4. Online ahead of print.

ABSTRACT

Vaccines work by inducing an immunological memory response to protect against infection or disease. More effective vaccines are required to improve protection of high-risk groups such as the elderly. Here we screen transcriptional signatures of T cell memory against repurposable drug signatures, identifying a subclass of lysine deacetylase inhibitors (KDACi) capable of promoting a memory precursor phenotype in primary T cells. Leveraging combined acetylomic, metabolomic, transcriptomic and epigenomic analyses, we identify enhanced glutaminolysis as the mechanism responsible for the KDACi effect, with selective inhibition reversing the changes induced by KDACi treatment. We validate the ability of a repurposable KDACi (sodium valproate) to promote immune memory in four murine models of infection and immunisation, with the effect reversed by concurrently inhibiting glutaminolysis. Finally, we undertake a human challenge study, which demonstrates a 10-fold increase in correlates of protection following seasonal influenza vaccination. These results reveal immune-metabolic adjuvant properties of repurposable lysine deacetylase inhibitors and demonstrate that systematic screening can identify both efficacy and mechanism of repurposable drugs.

PMID:42362565 | DOI:10.1038/s41467-026-74866-4

Care-pathway decision support improves non-specialist vet clinical decision making in dogs with myelopathy

Recent Publications - Thu, 25/06/2026 - 11:00

J Vet Intern Med. 2026 May 4;40(3):aalag118. doi: 10.1093/jvimsj/aalag118.

ABSTRACT

BACKGROUND: Non-specialist vets are often required to make decisions in the absence of specialist knowledge and support. Care pathways (CPs) use knowledge engineering to convert expert knowledge into a computer-interpretable format, delivered to clinicians at the point-of-care via patient-specific clinical decision recommendations.

HYPOTHESIS/OBJECTIVES: Non-specialist vets make diagnostic and management decisions that are more consistent with specialists when they have access to CP decision support.

ANIMALS: Clinical information from 8 historical cases of dogs with myelopathy presenting to a university referral hospital with para/tetra-paresis/plegia were used for the study.

METHODS: A CP was developed to prioritize differential diagnoses and provide management recommendations for cases of dogs with myelopathy resulting in para/tetra-paresis/plegia. A crossover study was then performed comparing answers 45 non-specialist vets and 17 final-year vet students gave to case-based questions for 8 clinical cases, with and without the use of the CP. Each participant answered half the questions without any decision support (CP-) and half the questions with CP decision support (CP+), with the question order randomized each time. Participant answers were then scored against a pre-agreed expert consensus, represented by the full score of 100 points.

RESULTS: Mean scores were improved by 40.4 points (95% CI [36.4, 44.4]), P < .05) for differential diagnosis listing and prioritization and 7.1 points (95% CI [2.3, 11.6]), P < .05) for management decisions when using the CP.

CONCLUSIONS AND CLINICAL IMPORTANCE: CP clinical decision support could be a useful adjunctive tool for non-specialist vets, particularly in supporting their ability to produce prioritized differential diagnoses.

PMID:42348907 | DOI:10.1093/jvimsj/aalag118

Scotty: lattice coincidences in the Protein Data Bank

Recent Publications - Wed, 24/06/2026 - 11:00

Acta Crystallogr D Struct Biol. 2026 Jul 1. doi: 10.1107/S2059798326005723. Online ahead of print.

ABSTRACT

The application Scotty, implemented within the Phasertng codebase, was used to perform a PDB-wide analysis of lattice coincidences. Using a broad definition of lattice coincidence, the number of distinct lattice clusters is approximately half the total number of crystallographic PDB entries. In over one thousand lattice clusters entries are reported in different space groups, consistent with pseudo-symmetric variation within a common lattice framework. Space-group frequencies computed at the lattice-coincidence level update those obtained by entry-based counting, and more accurately reflect priors for novel crystal forms. Combining lattice clustering with sequence identity and deposited oligomeric annotations reveals multiple cases of inconsistent biological assembly assignments among structures sharing near-identical lattices, suggesting an opportunity to improve annotations. The survey also identifies a range of protein systems forming extended in cellulo paracrystalline arrays, including storage, sequestration, toxin and membrane-associated proteins, an understudied area of structural biology. Overall, the results demonstrate that lattice-level analysis provides a valuable perspective on macromolecular self-association.

PMID:42339564 | DOI:10.1107/S2059798326005723

Scotty: lattice coincidences for macromolecular crystallographic phasing

Recent Publications - Wed, 24/06/2026 - 11:00

Acta Crystallogr D Struct Biol. 2026 Jul 1. doi: 10.1107/S2059798326005711. Online ahead of print.

ABSTRACT

When a macromolecular crystal lattice targeted for study is closely related to a previously studied crystal lattice, phasing the target crystal by difference (fast-)Fourier transform (DFFT) methods is preferable to performing molecular replacement. The application Scotty, within the Phasertng codebase, is software for the identification of coincident lattices and downstream processing. All crystallographic PDB entries are organized into a scikit-learn `BallTree' index under the Niggli cell distance metric `NCDist'. Nearest neighbours under the metric are progressed to test structure-factor intensity correlation. The structure from the lattice with the highest correlation with the target is used to phase the target lattice, and the coordinates are taken forward to coordinate refinement using a wide convergence radius protocol. The method can identify lattice coincidences accounting for very significant non-isomorphism. The nearest-neighbour search is space-group agnostic, so that coincident lattices are identified even when the nominal space groups are different, the symmetry of one lattice being described as a subgroup of the other or a higher metric symmetry.

PMID:42339563 | DOI:10.1107/S2059798326005711

Genomic epidemiology and evolutionary analysis of Lassa virus from small mammals suggest bidirectional viral movement across humans and animals

Recent Publications - Wed, 24/06/2026 - 11:00

Virus Evol. 2026 Jun 1;12(1):veag032. doi: 10.1093/ve/veag032. eCollection 2026.

ABSTRACT

Lassa fever is a viral haemorrhagic fever that poses a persistent public health threat in several West African countries, particularly Nigeria. The scarcity of Lassa virus (LASV) sequences isolated from small mammal reservoirs limits our knowledge and understanding of LASV genomic diversity and transmission dynamics. To address this knowledge gap, we sampled 1189 small mammals, including mice, rats, and shrews, from two LASV-endemic states in southern Nigeria (Ondo and Ebonyi States) and tested them for the presence of LASV RNA using reverse transcription-quantitative polymerase chain reaction. Selected quantitative polymerase chain reaction-positive samples were subjected to whole genome sequencing and small mammal speciation through next-generation sequencing outputs. We recorded an overall polymerase chain reaction positivity rate of 61.6%, with rat species demonstrating the highest LASV prevalence. We also conducted a serosurvey of 269 small rodents using indirect Enzyme-Linked Immunosorbent Assay (ELISA) and obtained an overall anti-LASV seroprevalence of 45%. Using the Nextera XT metagenomic sequencing protocol, we produced 55 LASV partial (n = 28) and full-length genomes (n = 27) from small mammals sampled, all of which clustered within sublineage 2g. LASV sequences generated from this study suggest that LASV variation is mostly driven by location, as isolates from this study tend to cluster more closely with other isolates collected from within the same region, rather than by collection date or host. However, samples collected from Ebonyi State were more closely related to isolates collected in Ondo State than to isolates from Edo, despite a larger physical distance. Overall, the data from this study suggest free movement of the virus across states in Nigeria, among humans and various non-human taxa. The finding of LASV in additional small mammal hosts suggests that the virus reservoir is vast and may include many small mammals not well-characterized.

PMID:42339070 | PMC:PMC13285998 | DOI:10.1093/ve/veag032