Feed aggregator

J Biol Chem. 2026 Aug 13:113450. doi: 10.1016/j.jbc.2026.113450. Online ahead of print.

ABSTRACT

Mycobacterium tuberculosis is the world's leading bacterial infectious agent. The absence of an effective vaccine and the rise of multi-drug resistant M. tuberculosis strains emphasize the need to identify novel targets for prevention and intervention strategies. Previously, the M. marinum orthologue of the aspartic protease PecA (PE_PGRS35) was found on the bacterial cell surface, after secretion by the specialized Type VII secretion system. PecA was shown to be responsible for the processing of secreted PE_PGRS proteins, including itself. Both M. marinum and M. tuberculosis encode two additional predicted aspartic proteases with similar secretion domains (PE_PGRS16 and PE26). The roles of the M. marinum PecA, PecB and PecC were studied using frameshift mutants generated by CRISPR-Cas9 technology. Numerous PecA substrates were identified using analysis of semi-tryptic peptides detected by proteomics of secreted, surface-associated protein fractions. The most abundant substrates are members of the PE and PPE protein families. In addition, analysis of semi-tryptic peptides revealed consensus cleavage sites. Interestingly, these cleavage sites were also situated within the Type VII secretion motif (YxxxD/E), thereby effectively removing the entire PE domain, further strengthening the notion that these domains function as secretion peptides. PecB and PecC were also predicted to process PE and PPE proteins, although to a lesser extent than PecA. Follow-up experiments revealed that PecC is involved in processing of a small subset of the PPE protein family. Finally, our evidence indicates that PecA functions similarly in M. tuberculosis, as PecA is also responsible for cleavage of PE_PGRS proteins in this species.

PMID:42595108 | DOI:10.1016/j.jbc.2026.113450

J Med Chem. 2026 Aug 13;69(15):17584-17601. doi: 10.1021/acs.jmedchem.6c00643.

ABSTRACT

CK2 is a constitutively active serine/threonine kinase implicated in cancer, viral infection, and neurodegeneration, but its conserved ATP-binding site and complex holoenzyme assembly have long made selective inhibition challenging. This Perspective discusses three complementary strategies for selective CK2 inhibition: targeting the CK2α/β interface with small molecules, disrupting the same interface with conformationally constrained peptides, and exploiting the cryptic αD pocket for dual-site inhibitor design. CK2α/β-interface inhibitors, including CAM187, CAM7117 and P8C9, established structurally validated routes to modulate holoenzyme assembly and β-dependent substrate phosphorylation. Validation of the αD pocket as a ligandable cryptosteric site enabled dual-site ligands such as CAM4066 and αD-directed inhibitors such as CAM4712, followed by related advances including AB668, KDX1381 and Biv5. These efforts culminated in APL-5125, a highly selective, subnanomolar dual-site inhibitor now in Phase 1/2 clinical evaluation.

PMID:42593905 | DOI:10.1021/acs.jmedchem.6c00643

J R Soc Med. 2026 Aug 12:1410768261475034. doi: 10.1177/01410768261475034. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate recruitment equity for NHS specialty training posts between 2021-2024, characterising demographics, quantifying appointment disparities by protected characteristics and assessing temporal trends.

DESIGN: Longitudinal cohort study using national recruitment data via annual Freedom of Information requests.

SETTING: National Health Service, UK.

PARTICIPANTS: All medical and surgical specialty training applications to NHS England (2021-2024).

MAIN OUTCOME MEASURES: Application success by protected characteristics.

RESULTS: Of 214,893 applications, 52,998 (24.7%) were appointed. Annual success rates fell from 12,419/37,971 (32.7%) in 2021 to 13,929/81,189 (17.2%) in 2024. Competitiveness increased but non-UK graduate applications did not reduce successful UK graduate numbers. Gender segregation persisted: surgical specialties had the highest proportion of male applicants, whereas for females this was observed in obstetrics and gynaecology. Female applicants had higher success rates than males (27.5% vs 22.2%; Δ5.3%, 95% CI 4.95-5.70, p < 0.001). Pregnant/maternity-leave candidates had lower success (21.3% vs 25.8%, Δ4.5%, 95% CI 3.15-5.82, p < 0.001), most markedly in paediatrics (Δ14.8%, 95% CI 8.95-20.58, p < 0.001) and surgery (Δ13.7%, 95% CI 7.60-19.82, p = 0.008). UK graduates outperformed non-UK graduates (40.7% vs 15.5%; Δ25.2%, 95% CI 24.8-25.6, p < 0.001). Adjusted for country of graduation, 15/15 minority ethnic groups had lower odds of success versus White-British, with steepest declines among Black Caribbean and Bangladeshi graduates.

CONCLUSIONS: Inequities persist in NHS specialty recruitment. Gender segregation remains and disparities disadvantage pregnant/maternity-leave applicants. Disparities impacting minority ethnic UK graduates have widened. While data constraints preclude adjusting for confounders, these consistent trends require continuous monitoring and targeted interventions to ensure equitable access.

PMID:42584039 | DOI:10.1177/01410768261475034

Methods Mol Biol. 2026;3069:187-201. doi: 10.1007/978-1-0716-5508-5_13.

ABSTRACT

The ability to specifically degrade one protein in a cell provides an immediate insight into any resulting phenotype and thus function that may be occluded by secondary effects using other techniques. The auxin-inducible degron is a method developed to achieve this end and is effective in mammalian and yeast cells. The approach is dependent on the recognition of a tagged target protein by an endogenous E3 ubiquitin ligase modified by the expression of a plant F-box protein. This approach was initially unsuccessful in trypanosomes, probably due to a lack of interaction between the endogenous E3 ubiquitin ligase and the plant F-box protein. This was overcome by expressing the entire rice E3 ubiquitin ligase in trypanosomes, and here we describe the production of the auxin-inducible degron competent cell lines and tagging of target genes.

PMID:42573698 | DOI:10.1007/978-1-0716-5508-5_13

ISME Commun. 2026 Jun 1;6(1):ycag130. doi: 10.1093/ismeco/ycag130. eCollection 2026 Jan.

ABSTRACT

Bacterial genomes represent dynamic ecological systems in which highly dynamic accessory genome element compositions drive evolution. Emerging evidence suggests that bacterial defence systems, which protect against phages and other genetic elements, can interact cooperatively, competitively, and antagonistically to influence horizontal gene transfer, shape phage susceptibility, and diversify genomes across environments. Recent ecological studies reveal non-random co-occurrence and avoidance patterns among defence systems, suggesting that these patterns may emerge from ecological and evolutionary interactions rather than chance. Hence, these patterns need exploring in the context of ecological niche and co-localization to identify putative functional compatibilities and elucidate how defence systems shape the accessory genome. To characterize these patterns, we analysed the distributions of defence systems and other accessory genome elements in a curated global dataset of 2940 Pseudomonas aeruginosa. Defence system content varied by ecological niche, with higher numbers in non-cystic fibrosis-derived isolates (average n = 7.9) compared to cystic fibrosis-derived isolates (average n = 6.5). There were also multiple associations (n = 426) and dissociations (n = 50) among defence systems, and among other accessory genome elements, many with a plausible biological explanation. We also found that defence and anti-defence systems engage in more interactions than other accessory genome element types (e.g. antimicrobial resistance genes, plasmids), suggesting that they are a major driving force in the ecological dynamics of bacterial genomes. These patterns provide new insights into the evolutionary forces shaping bacteria and provide a valuable resource of robustly quantitated interactions, establishing a baseline for future mechanistic and ecological investigations of defence system interactions.

PMID:42571538 | PMC:PMC13452453 | DOI:10.1093/ismeco/ycag130

Brief Bioinform. 2026 Jul 3;27(4):bbag425. doi: 10.1093/bib/bbag425.

ABSTRACT

Biologically informed neural networks are increasingly adopted in bioinformatics under the premise that embedding biological knowledge into model architectures yields more accurate and interpretable predictions. This approach has driven a growing literature of pathway-informed models aiming to move beyond black-box learning by explicitly encoding biological structure. However, it remains unclear whether these models exploit biological knowledge or instead benefit from a different inductive bias. Here, we systematically investigate this question across 29 state-of-the-art pathway-informed neural networks by explicitly decoupling biological annotations from network architecture. For each evaluable model, we implement a structure-matched randomization protocol, in which pathway annotations are replaced with random associations while preserving sparsity and architectural constraints, allowing for a direct comparison under controlled conditions. Across multiple prediction tasks, datasets, and evaluation metrics, the randomized models consistently match or outperform their biologically informed counterparts. Moreover, pathway-informed models show no systematic advantage in interpretability: randomized models recover disease-associated biomarkers with comparable accuracy and yield highly correlated feature rankings. Our results reveal that the performance gains commonly attributed to biological pathway integration arise predominantly from sparsity-induced regularization rather than from biological knowledge itself. We provide a general evaluation workflow to test whether biological priors contribute predictive information beyond sparsity, offering practical guidance for the development of biology-aware neural networks. The code implementing the proposed methodology is available on GitHub at https://github.com/compbiomed-unito/Pathway_Randomization.

PMID:42561153 | DOI:10.1093/bib/bbag425

Curr Opin Virol. 2026 Aug 5;77:101571. doi: 10.1016/j.coviro.2026.101571. Online ahead of print.

ABSTRACT

Potyviruses and cucumoviruses (exemplified by cucumber mosaic virus (CMV)) are highly divergent taxa of plant-infecting positive-sense RNA viruses. However, they face similar challenges. They must overcome host antiviral resistance mechanisms, for example, RNA silencing or resistance mediated by the phytohormone salicylic acid, and they must do this across a very diverse range of host species. Although in some hosts potyviruses and CMV are seedborne, they are predominantly transmitted by aphid vectors. Both have acquired mechanisms for subverting host defences, particularly those controlled by jasmonic acid, to manipulate vector behaviour and increase transmission. This article compares how CMV and potyviruses took distinct evolutionary paths to overcome these common challenges. Potyviruses diverged into numerous distinct viral species to exploit different hosts and co-opted many gene products, including P1, HC-Pro, NIa, VPg, 6K2 and NIb, to effector roles. In contrast, CMV strains show less divergence but still exploit wide host ranges, and predominantly use the 2b counter-defence protein for subverting and manipulating host responses.

PMID:42556132 | DOI:10.1016/j.coviro.2026.101571

Emerg Microbes Infect. 2026 Aug 3:2713851. doi: 10.1080/22221751.2026.2713851. Online ahead of print.

ABSTRACT

Human noroviruses (HuNoV) are the most common cause of viral gastroenteritis worldwide, causing sporadic cases and outbreaks. Noroviruses that infect wild and domestic animals, including pigs and dogs, are genetically related to human noroviruses, increasing the potential for cross-species transmission. To investigate the potential of noroviruses to cross the species barrier, we used porcine, canine, and avian precision-cut intestinal slices. We show that human norovirus virus-like particles (VLPs) bind to pig and dog intestinal tissue and are taken up with a similar efficiency as the porcine and canine noroviruses, respectively. In contrast, no binding or internalization of human, porcine, or canine noroviruses was detected in chicken tissue. We further showed that human norovirus replicates in pig intestinal tissue. In contrast, while animal noroviruses attached to human intestinal cells, intracellular uptake was limited. This suggests that human-to-animal transmission is more likely than animal-to-human transmission and that viral uptake likely presents a species barrier.

PMID:42546135 | DOI:10.1080/22221751.2026.2713851

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

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

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

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

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

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

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

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

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

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

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

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