Proc Natl Acad Sci U S A. 2025 Jul 15;122(28):e2414331122. doi: 10.1073/pnas.2414331122. Epub 2025 Jul 10.

ABSTRACT

Excessive degradation of the colonic mucin layer by Bacteroides within the human gut microbiota drives inflammatory bowel disease (IBD) in mice. Bacterial carbohydrate sulfatases are key enzymes in gut colonization, and they are elevated in human IBD and correlate with disease severity. Selective inhibitors of carbohydrate sulfatases could function as sulfatase-selective drugs, allowing precise control of sulfatase activity while preserving these otherwise beneficial bacteria. Arylsulfamates are covalent inhibitors that target a catalytic formylglycine residue of steroid sulfatases, a residue that is also conserved in carbohydrate sulfatases. Here, we find that a library of aryl- and carbohydrate sulfamates is ineffective against carbohydrate sulfatases, yet can inhibit human gut microbiota (HGM) species grown on sulfated glycans. Leveraging thermal proteome profiling (TPP), we identify a lipid kinase as the target responsible for these effects. This work highlights the imperative for developing specific inhibitors targeting carbohydrate sulfatases and reveals the adverse effects that arylsulfamates have on Bacteroides species of the HGM.

PMID:40638084 | DOI:10.1073/pnas.2414331122

Methods Mol Biol. 2025;2953:167-187. doi: 10.1007/978-1-0716-4694-6_11.

ABSTRACT

A wide range of technologies have been developed to study protein-protein interactions and to map comprehensive protein interaction networks. In recent years, advances in proximity labeling methods, coupled to protein identification by mass spectrometry, have led to exponential growth in the popularity of these methods. In this chapter, we present a detailed protocol using TurboID in Arabidopsis thaliana seedlings, using membrane-bound transcription factors as a case study. Additionally, we outline the workflow for analyzing mass spectrometry data to identify putative protein interactors.

PMID:40638048 | DOI:10.1007/978-1-0716-4694-6_11

J Cardiovasc Transl Res. 2025 Jul 10. doi: 10.1007/s12265-025-10658-3. Online ahead of print.

ABSTRACT

Cachexia, often seen in chronic heart failure (CHF), worsens patient outcomes and survival. Early detection is crucial, and circulating miRNAs offer potential as biomarkers linking heart function, inflammation, and cachexia. This study aimed to identify plasma miRNAs associated with cachexia in CHF and assess their diagnostic and prognostic value. Plasma samples from 150 newly diagnosed CHF patients were analyzed using next-generation sequencing (NGS) and validated by qRT-PCR. A signature of elevated miRNA-628 and reduced miRNA-6803 (↑miRNA-628+↓miRNA-6803) was associated with poor nutritional status, abnormal lab results, and higher cachexia risk. Combining this signature with inflammatory markers perfectly distinguished cachectic from non-cachectic patients (AUC=1.0). This profile increased cachexia risk 19-fold and was linked to significantly shorter survival (median 14 vs. 41 months). Thus, the identified miRNA signature offers strong predictive and diagnostic potential and could complement clinical assessments of CHF patients' nutritional status.

PMID:40637997 | DOI:10.1007/s12265-025-10658-3

J Exp Bot. 2025 Jul 10:eraf216. doi: 10.1093/jxb/eraf216. Online ahead of print.

NO ABSTRACT

PMID:40637838 | DOI:10.1093/jxb/eraf216

Arch Virol. 2025 Jul 10;170(8):177. doi: 10.1007/s00705-025-06366-7.

ABSTRACT

Grapevine red blotch virus (GRBV; species Grablovirus vitis, genus Grablovirus, family Geminiviridae) poses a significant threat to viticulture worldwide, impacting grapevine health and wine quality. Here, we report the first detection and tracing of GRBV in Australia and provide a summary of a subsequent survey to determine the extent of GRBV distribution in Western Australia. Additionally, the study introduces a tiled amplicon sequencing method, which, when combined with long-read nanopore sequencing, enables rapid GRBV genome sequencing. Our analysis suggests a single introduction of GRBV from North America to Australia through the state of Victoria and subsequently to Western Australia. Finally, this study provides insight into the epidemiology of GRBV, based on strain variation and distribution, which is a crucial step in supporting an emergency biosecurity response and implementing effective control measures to safeguard the sustainability of the wine industry in Australia.

PMID:40637789 | DOI:10.1007/s00705-025-06366-7

Am J Physiol Gastrointest Liver Physiol. 2025 Jul 10. doi: 10.1152/ajpgi.00130.2025. Online ahead of print.

ABSTRACT

Host-gut microbiota interactions may impact intestinal function during sustained periods of high energy demands. Whether energy status, reflecting the balance between energy intake and expenditure, impacts those interactions is unknown. This study determined the effects of energy status during sustained high energy demands on intestinal function and the gut microbiota. Ten healthy men completed a randomized, crossover study that included baseline (BL) testing, and two 72-hour periods of high physical activity-induced energy demands (HPA; ~2300kcal/d physical activity energy expenditure) followed by a 7-day recovery period (REC). During HPA, diets designed to elicit a ~45% energy deficit (DEF; -2047±920kcal/d) or maintain energy balance within ±10% total daily energy expenditure (BAL; 689±852kcal/d) were provided. Intestinal permeability and transit time, fecal microbiota composition and gene content, fecal short chain fatty acids (SCFA) and gastrointestinal symptoms were measured. Intestinal permeability was 17% higher during HPA-DEF versus HPA-BAL (P=0.02) and colonic transit time was slower during HPA-DEF versus HPA-BAL (mean difference [95%CI] =-764 min [- 1345, -183]) and BL (-643min [-1178, -108]) (P=0.02). Fecal microbiota species richness (-40 species [-66, -13], P=0.01) and relative abundances of multiple species (log2 fold difference< -5, P<0.02) were lower during HPA-BAL versus HPA-DEF but did not differ between conditions during REC. Small bowel transit time, gastrointestinal symptoms, fecal microbiota gene pathways, and fecal SCFA did not differ between conditions. Findings suggest that increasing dietary intake to prevent energy deficit may benefit intestinal health and function during short term periods of high energy demands without sustained impacts on the gut microbiota.

PMID:40637323 | DOI:10.1152/ajpgi.00130.2025

Nucleic Acids Res. 2025 Jul 8;53(13):gkaf530. doi: 10.1093/nar/gkaf530.

ABSTRACT

Disassembly of the replication machinery (replisome) from chromatin is an active process driven by two ubiquitin ligases Cul2LRR1 and TRAIP, which both target the Mcm7 subunit of the replicative helicase for ubiquitylation. Uncontrolled unloading of replisomes during S-phase would be disastrous for genome stability and cell viability. On the other hand, replisomes retained on under-replicated DNA in mitosis require removal to allow access and processing of the DNA before cell division. TRAIP ubiquitylates replisomes in mitosis but can also act in specific situations during S-phase. However, we do not know how TRAIP's activity is regulated to stop uncontrolled replisome unloading. Here we show that TRAIP activity towards replisomes is not regulated at the level of interaction with the substrate: it interacts with terminated replisomes in S-phase without ubiquitylation. However, in mitosis, TRAIP is phosphorylated by cyclin-dependent kinases (CDKs) and this phosphorylation is essential for mitotic replisome unloading. CDK phosphorylation of TRAIP stimulates its autoubiquitylation activity and ubiquitylation of replisomes isolated from mitotic chromatin. The phosphorylation of TRAIP is also important in human cells for TRAIP functions during MiDAS. Although essential during mitosis, the CDK-driven phosphorylation of TRAIP is not sufficient to activate uncontrolled unloading of replisomes in S-phase.

PMID:40637231 | DOI:10.1093/nar/gkaf530

Soft Matter. 2025 Jul 10. doi: 10.1039/d5sm00340g. Online ahead of print.

ABSTRACT

We study the first-passage-time (FPT) properties of an active Brownian particle under stochastic resetting to its initial configuration, comprising its position and orientation, to reach an absorbing wall in two dimensions. We employ a renewal framework for the stochastic resetting process and use a perturbative approach for small Péclet numbers, measuring the relative importance of self-propulsion with respect to diffusion. This allows us to derive analytical expressions for the survival probability, the FPT probability density, and the associated low-order moments. Depending on their initial orientation, the minimal mean FPT for active particles to reach the boundary can both decrease and increase relative to the passive counterpart. The associated optimal resetting rates depend non-trivially on the initial distance to the boundary due to the intricate interplay of resetting, rotational Brownian noise, and active motion.

PMID:40637124 | DOI:10.1039/d5sm00340g

Exp Biol Med (Maywood). 2025 Jun 25;250:10607. doi: 10.3389/ebm.2025.10607. eCollection 2025.

ABSTRACT

Fentanyl is a potent and short-acting opioid that is often given to pediatric patients during surgery to relieve pain and as an adjunct to anesthesia. Its effects on the developing brain are yet to be determined. In the present study, commercially available human neural stem cells (NSCs) were used to model the effects of fentanyl on the developing human brain. We determined the dose dependent effects and temporal relationships between fentanyl exposures and NSC health, viability, and differentiation. Markers of mitochondrial health [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide (MTT)] and cell death/damage [lactate dehydrogenase (LDH)] were monitored to determine the dose response effects of fentanyl on NSC viability. In addition, lipidomics analysis was conducted to investigate lipid profile changes in differentiated neural cells treated with fentanyl. Fentanyl did not cause a significant increase in LDH release, nor MTT reduction after 24-h exposure at concentrations of 0.5, 1.0, 3.0, 10, or 100 μM, for both NSCs and differentiated neural cells. Lipidomics data showed the top 15 most variable important in projection (VIP) lipid species (the higher the VIP scores, the bigger changes in treated groups vs. controls), including lysophosphatidylcholines (LPCs), lysophosphatidylethanolamines (LPEs), ceramides (CER), cholesterol esters (ChEs) and sphingosine (SPH). The lipidomic data indicate that LPC (16:0), LPC (16:1), LPC (18:1), CER (d18:0_22:0), CER (d18:2_18:0), CER(d18:2_24:1) were significantly increased, and only ChE (24:5) and SPH (d18:1) were significantly decreased in the highest dose group versus control. These data indicated that fentanyl exposure (24-h) did not induce detectable cell death. However, a lipidomic analysis indicated that fentanyl may affect immature neural cell functions through modifying lipid composition and lipid metabolism. These data indicated that despite the absence of clear neurodegeneration, fentanyl may still have a negative impact on the developing brain.

PMID:40636749 | PMC:PMC12237720 | DOI:10.3389/ebm.2025.10607

Front Microbiol. 2025 Jun 25;16:1603255. doi: 10.3389/fmicb.2025.1603255. eCollection 2025.

ABSTRACT

BACKGROUND: Precise detection of microbial genetic variation (MGV) at the strain level is essential for reliable disease diagnosis, pathogen surveillance, and reproducible research. Current methods, however, are constrained by limited sensitivity, specificity, and dependence on culturing. To address these challenges, we developed MGV-Seq, an innovative culture-independent approach that integrates multiplex PCR, high-throughput sequencing, and bioinformatics to analyze multiple dispersed nucleotide polymorphism (MNP) markers, enabling high-resolution strain differentiation.

METHODS: Using Xanthomonas oryzae as a model organism, we designed 213 MNP markers derived from 458 genome assemblies. Method validation encompassed reproducibility, accuracy, sensitivity (detection limit), and specificity using laboratory-adapted strains, artificial DNA mixtures, and uncultured rice leaf samples. Performance was benchmarked against whole-genome sequencing (WGS) and LoFreq variant calling.

RESULTS: MGV-Seq achieved 100% reproducibility and accuracy in major allele detection, with sensitivity down to 0.1% (n = 12 strains) for low-abundance variants and significantly higher specificity than LoFreq. Analysis to 40 X. oryzae strains revealed widespread heterogeneity (90% of strains) and misidentification (e.g., HN-P5 as Xoc). Homonymous strains exhibited significant genetic and phenotypic divergence, attributed to contamination rather than mutation. MGV-Seq successfully identified dominant strains and low-frequency variants in rice leaf samples and authenticated single-colony strains with 100% major allele similarity.

CONCLUSION: MGV-Seq establishes a robust, high-throughput solution for strain identification, microevolution monitoring, and authentication, overcoming limitations of culture-dependent and metagenomics-based methods. Its applicability extends to other microorganisms, offering potential for clinical, agricultural, and forensic diagnostics.

PMID:40636508 | PMC:PMC12237947 | DOI:10.3389/fmicb.2025.1603255

Front Microbiol. 2025 Jun 25;16:1617388. doi: 10.3389/fmicb.2025.1617388. eCollection 2025.

ABSTRACT

INTRODUCTION: Rumen microbiota and host metabolites play a key role in regulating ruminant production performance and physiological adaptation. However, the interplay between host physiological status and rumen microbial-metabolite dynamics across lactation stages in buffaloes remains unclear.

METHODS: This study employed a multi-omics approach, integrating metagenomic and serum metabolomic analyses, to investigate microbial remodeling and metabolic adaptations in buffaloes during lactation and dry periods.

RESULTS: Metagenomic analysis revealed increased abundances of Anaerovibrio, Succiniclasticum, and Methanobrevibacter_A during lactation, associated with lipid hydrolysis, propionate production, and methanogenesis, respectively. Glycoside hydrolase families GH2, GH3, GH5, and GH13 were enriched, indicating elevated carbohydrate degradation potential. In contrast, Butyrivibrio, Fibrobacter, and Eubacterium_Q were predominant during the dry period, contributing to fiber degradation and butyrate synthesis. Functional pathways related to niacin metabolism, bicarbonate reabsorption, and neuroactive ligand-receptor interaction were significantly upregulated during lactation. Metabolomic profiling identified lactation-enriched metabolites such as indole-3-methylacetate, D-maltose, and gluconic acid, correlating with immune and metabolic indicators (e.g., IgA, glucose, LDL). Conversely, dry period metabolites such as 1-methylhistidine and 5-hydroxyindoleacetic acid indicated physiological shifts toward tissue repair and stress mitigation.

DISCUSSION: The integrative analysis revealed that host physiological demands during lactation coordinate rumen microbial restructuring to enhance triglyceride degradation, fatty acid biosynthesis, and energy mobilization, thereby supporting milk production. These findings provide novel insights into the host-driven microbiome-metabolite axis underlying lactation in buffaloes.

PMID:40636496 | PMC:PMC12237897 | DOI:10.3389/fmicb.2025.1617388

Front Microbiol. 2025 Jun 25;16:1621463. doi: 10.3389/fmicb.2025.1621463. eCollection 2025.

ABSTRACT

A rapidly changing climate has resulted in increasing challenges for farmers. This has led to an increase in demand for beneficial microbes to help fight these challenges faced by farmers, improving crop production under harsh conditions. Increasing temperatures caused by the changing climate will also affect the dairy industry in temperate climates around the world. This has resulted in an increasing importance of warm-season pasture grasses to fill the feed gaps left by the affected temperate grasses. In this study, we assessed the microbial communities present in commercially available warm-season pasture grass seeds. We utilised amplicon metagenomics to profile and compare the bacterial and fungal communities of seeds from three different genera of warm-season pasture grasses. Microbial isolations have also been performed to assess the culturability of the seed microbiome. Significant differences in drivers of bacterial and fungal communities within warm-season pasture grass seeds were observed. In addition, most of the bacteria present in high abundance were found to be culturable, while a relatively lower percentage of abundant fungi were culturable. Analysis of the bacterial communities showed considerable variation between different distributors, possibly driven by differing seed processing methods. This variation indicates that the bacterial communities could be manipulated by providing different bacteria to the seed to promote plant growth under different conditions. In contrast, the fungal communities were more strongly driven by the genetics of the respective host genera. This suggests that differences in fungal strain levels could be exploited for modification of fungal microbiome effects.

PMID:40636492 | PMC:PMC12237998 | DOI:10.3389/fmicb.2025.1621463

Front Cell Infect Microbiol. 2025 Jun 25;15:1561443. doi: 10.3389/fcimb.2025.1561443. eCollection 2025.

ABSTRACT

A description of the construction of the bioengineered P4-EKORhE and a comprehensive method for producing very high yields (up to 1012 particles per millilitre) enable the use of virus-like particles to transduce genetically encoded antimicrobials through a combination of synthetic biology and optimised upstream and downstream processing. The final product, a gene-delivered antimicrobial in the form of the multi-lysin cassette, is fully functional before and after packaging within P4-EKORhE particles. The antimicrobial activity of the multi-lysin cassette, characterised by its lysis proteins, was tested in vivo in both pure bacterial Escherichia coli cultures and a model of phage infection in co-culture with A549 immortalised human epithelial tissue cells. This work exemplifies several bioproduction methods and demonstrates how the virology of the P4 and P2 phages can be harnessed to establish a bioprocess for producing transducing particles at very high yields, avoiding contamination by the natural virus while maintaining the antimicrobial effectiveness of the final product.

PMID:40636261 | PMC:PMC12239096 | DOI:10.3389/fcimb.2025.1561443

Clin Transl Sci. 2025 Jul;18(7):e70284. doi: 10.1111/cts.70284.

ABSTRACT

The growing availability of biomedical data offers vast potential to improve human health, but the complexity and lack of integration of these datasets often limit their utility. To address this, the Biomedical Data Translator Consortium has developed an open-source knowledge graph-based system-Translator-designed to integrate, harmonize, and make inferences over diverse biomedical data sources. We announce here Translator's initial public release and provide an overview of its architecture, standards, user interface, and core features. Translator employs a scalable, federated, knowledge graph framework for the integration of clinical, genomic, pharmacological, and other biomedical knowledge sources, enabling query retrieval, inference, and hypothesis generation. Translator's user interface is designed to support the exploration of knowledge relationships and the generation of insights, without requiring deep technical expertise and gradually revealing more detailed evidence, provenance, and confidence information, as needed by a given user. To demonstrate Translator's application and impact, we highlight features of the user interface in the context of three real-world use cases: suggesting potential therapeutics for patients with rare disease; explaining the mechanism of action of a pipeline drug; and screening and validating drug candidates in a model organism. We discuss strengths and limitations of reasoning within a largely federated system and the need for rich concept modeling and deep provenance tracking. Finally, we outline future directions for enhancing Translator's functionality and expanding its data sources. Translator represents a significant step forward in making complex biomedical knowledge more accessible and actionable, aiming to accelerate translational research and improve patient care.

PMID:40635371 | DOI:10.1111/cts.70284

Glia. 2025 Jul 9. doi: 10.1002/glia.70053. Online ahead of print.

ABSTRACT

Astrocytes provide physical and metabolic support for neurons, regulate the blood-brain barrier, and react to injury, infection, and disease. When astrocytes become reactive, maintenance of the inflammatory state and its functional implications throughout chronic neuroinflammation are all poorly understood. Several models of acute inflammation have revealed astrocyte subpopulations that go beyond a two-activation state model, instead encompassing distinct functional subsets. However, how reactive astrocyte (RA) subsets evolve over time during chronic inflammatory disease or infection has been difficult to address. Here we use a prolific human pathogen, Toxoplasma gondii, that causes lifelong infection in the brain alongside a Lcn2CreERT2 reporter mouse line to examine reactive astrocyte subsets during chronic neuroinflammation. Single-cell RNA sequencing revealed diverse astrocyte populations including transcriptionally unique Lcn2CreERT2+ RAs which change over the course of infection in a subset-dependent manner. In addition to an immune-regulating Lcn2CreERT2+ astrocyte population enriched with gene transcripts encoding chemokines CCL5, CXCL9, CXCL10, and receptors CCR7 and IL7R, a specific subset of Lcn2CreERT2+ astrocytes highly expressed transthyretin (Ttr), a secreted carrier protein involved in glycolytic enzyme activation and potential vasculature regulation and angiogenesis. These findings provide novel information about the evolution and diversity of reactive astrocyte subtypes and functional signatures at different stages of infection, revealing an undocumented role for transthyretin-expressing astrocytes in immune regulation at the central nervous system (CNS) vasculature.

PMID:40635167 | DOI:10.1002/glia.70053

BMC Complement Med Ther. 2025 Jul 9;25(1):247. doi: 10.1186/s12906-025-04998-5.

ABSTRACT

BACKGROUND: The use of natural health products (NHP) is constantly increasing worldwide. Among the most NHP consumed in the Arabian Peninsula are the resins of Commiphora myrrha (C. myrrha) tree. Consumption of C. myrrha may result in herb-drug interactions mediated by drug-metabolizing cytochrome P-450 (CYP) enzymes in the liver, which could lead to serious health consequences for patients. This study aims to determine the herb-drug interactions based on the induction of predominant CYP 2C9 by a non-toxic boiled aqueous extract of C. myrrha and to unveil the potential involvement of xenobiotic-sensing nuclear receptors such as transcription factor Pregnane X Receptor (PXR) in CYP 2C9 induction, and to predict the molecular interactions of PXR with C. myrrha-derived metabolite(s).

METHODS: Cytotoxic effect of boiled aqueous extract of C. myrrha resins in cultured liver carcinoma Hep G2 cells was assessed using MTT assay. CYP 2C9 gene and protein expression levels were evaluated using reverse transcription-quantitative polymerase chain reaction and Western blot. Nuclear receptor binding assays, chemical analysis and molecular docking prediction were performed using specific kits, liquid chromatography-mass spectrometry time-of-flight, and in silico software, respectively.

RESULTS: Tested at low concentrations (0.01-10 µg/mL) devoid of anti-proliferative effects, boiled C. myrrha resin aqueous extract upregulated CYP 2C9 gene and protein expressions in a dose-dependent manner, reaching a mean expression level exceeding 3.0-fold change in Hep G2 cells, compared with the basal level expressed in untreated cells. Furthermore, the use of the nuclear receptor binding assays confirmed the binding between C. myrrha metabolite(s) and PXR, while no binding to the other xenobiotic-sensing nuclear receptor, the constitutive androstane receptor (CAR), was observed. Chemical analysis and computational molecular docking using in silico studies revealed that a few C. myrrha resin-derived metabolites are strongly bound to PXR. In particular, the identified metabolite named commic acid E exhibited a predicted molecular docking score close to that of a native PXR ligand, suggesting C. myrrha metabolite(s) as potential PXR agonists.

CONCLUSIONS: Although in vivo studies are needed, this study cautions patients, healthcare providers, and governmental regulators against the consumption of C. myrrha preparations with a high potential for herb-drug interactions through drug-metabolizing CYP 2C9 enzyme induction, which could affect drug efficacy.

PMID:40634953 | DOI:10.1186/s12906-025-04998-5

Nature. 2025 Jul 9. doi: 10.1038/s41586-025-09231-4. Online ahead of print.

ABSTRACT

In the past decade, ancient protein sequences have emerged as a valuable source of data for deep-time phylogenetic inference1-4. Still, even though ancient proteins have been reported from the Middle-Late Miocene5,6, the recovery of protein sequences providing subordinal-level phylogenetic insights does not exceed 3.7 million years ago (Pliocene)1. Here, we push this boundary back to 21-24 million years ago (Early Miocene) by retrieving enamel protein sequences of a rhinocerotid (Epiaceratherium sp.; CMNFV59632) from Canada's High Arctic. We recover partial sequences of seven enamel proteins and more than 1,000 peptide-spectrum matches, spanning at least 251 amino acids. Endogeneity is in line with thermal age estimates and is supported by indicators of protein damage, including several spontaneous and irreversible chemical modifications accumulated during prolonged diagenesis. Bayesian tip-dating places the divergence time of CMNFV59632 in the Middle Eocene-Oligocene, coinciding with a phase of high rhinocerotid diversification7. This analysis identifies a later Oligocene divergence for Elasmotheriinae, weakening alternative models suggesting a deep basal split between Elasmotheriinae and Rhinocerotinae8,9. The findings are consistent with hypotheses on the origin of the enigmatic fauna of the Haughton Crater, which, in spite of considerable endemism, has similarity to distant Eurasian faunas10,11. Our findings demonstrate the potential of palaeoproteomics in obtaining phylogenetic information from a specimen that is approximately ten times older than any sample from which endogenous DNA has been obtained so far.

PMID:40634620 | DOI:10.1038/s41586-025-09231-4

Nature. 2025 Jul 9. doi: 10.1038/s41586-025-09270-x. Online ahead of print.

ABSTRACT

Wild plants can contribute valuable genes to their domesticated relatives1. Fertility barriers and a lack of genomic resources have hindered the effective use of crop-wild introgressions. Decades of research into barley's closest wild relative, Hordeum bulbosum, a grass native to the Mediterranean basin and Western Asia, have yet to manifest themselves in the release of a cultivar bearing alien genes2. Here we construct a pangenome of bulbous barley comprising 10 phased genome sequence assemblies amounting to 32 distinct haplotypes. Autotetraploid cytotypes, among which the donors of resistance-conferring introgressions are found, arose at least twice, and are connected among each other and to diploid forms through gene flow. The differential amplification of transposable elements after barley and H. bulbosum diverged from each other is responsible for genome size differences between them. We illustrate the translational value of our resource by mapping non-host resistance to a viral pathogen to a structurally diverse multigene cluster that has been implicated in diverse immune responses in wheat and barley.

PMID:40634612 | DOI:10.1038/s41586-025-09270-x

Leukemia. 2025 Jul 9. doi: 10.1038/s41375-025-02683-7. Online ahead of print.

ABSTRACT

ETV6::RUNX1 leukemia is the second most common subtype of childhood B cell acute lymphoblastic leukemia (B-ALL). Although it generally has a low relapse risk, a significant proportion of B-ALL relapses occur within this subtype due to its relatively high incidence. Measurable residual disease at the end of induction therapy is a well-established biomarker predicting treatment outcomes, while no genomic biomarkers are routinely applied in clinics. In this study, we used multiomic data from ETV6::RUNX1 leukemias to identify genomic features predictive of therapy response at disease presentation. In the deeply characterized sub-cohort we discovered that fast-responding cases frequently exhibited the APOBEC mutational signature and the gene expression signature of high cell cycle activity. In contrast, rearrangements of IGK genes were more frequent in slow responders. Additionally, response-related mutations were identified in transcriptional regulators and tumor suppressor genes (INTS1, NF1, TP53). Copy number analysis revealed that fast responders harbored more frequent deletions of chr12 p-arm, leading to transcriptomic changes affecting genes associated with induction therapy response (KRAS, FKBP4), while a shorter gain in chr12 was more common in slow responders. The identified genetic and transcriptomic markers of treatment sensitivity pave the way for improved disease classification at presentation, potentially improving clinical outcomes.

PMID:40634509 | DOI:10.1038/s41375-025-02683-7

Nat Commun. 2025 Jul 9;16(1):6335. doi: 10.1038/s41467-025-61676-3.

ABSTRACT

Extensive gene loss is a hallmark of rediploidization following polyploidization, but its molecular basis remains unclear: whether it occurs primarily through pseudogenization or DNA deletion. Here, we examine pseudogenization in collinear segments from ancient whole-genome multiplications (WGMs) across 12 angiosperms. Although total pseudogenes are abundant, we find far fewer WGM-derived pseudogenes than expected if pseudogenization and DNA deletion contribute equally to gene loss. Simulations of neutrally evolving pseudogenes indicate that, if DNA deletion is absent, pseudogenes should be detectable for far longer than observed in the paleo-polyploid genomes, suggesting gene loss driven by DNA deletion. Analyses of three neo-autopolyploid genomes confirm this pattern: among substantial gene loss, DNA deletions occur on average 1.5 times more frequently than pseudogenization. Our findings imply that gene loss post-polyploidization primarily takes place via DNA deletion, enabled by a genomic environment with an elevated recombination rate created by WGMs. In contrast, small-scale duplications yield scattered duplicated genes, which appear less exposed to deletion and hence result in a high number of pseudogenes. This model is further reinforced by an enrichment of WGM-derived pseudogenes in high recombination regions. Moreover, some pseudogenes may govern a function, as indicated by non-neutral Ka/Ks ratios and overlap with lncRNAs.

PMID:40634370 | DOI:10.1038/s41467-025-61676-3