Mol Ther. 2025 Jul 28:S1525-0016(25)00577-5. doi: 10.1016/j.ymthe.2025.07.041. Online ahead of print.

ABSTRACT

Spinal cord injury (SCI) disrupts communication between the brain and the spinal circuits, resulting in severe motor, sensory, and autonomic dysfunctions. Transplantation of neural progenitor cells (NPC) has been demonstrated to provide multiple benefits; however, limited graft survival and neuronal differentiation must be overcome to achieve improved results. Here, we explore the optogenetic modulation of rat spinal cord-derived NPC expressing channelrhodopsin-2 (ChR2), through AAV9-mediated transduction, transplanted into the sub-acute stage after SCI. Daily blue-light stimulation and ChR2-dependent activation control of the modified NPC significantly enhanced locomotor skills, run speed, sustained walking coordination, and body stability in a rat SCI model. Engrafted rat NPC-ChR2 reduces astrocytic reactivity and the injured area volume; preserves a higher number of descending propriospinal neurons above the injury; and a higher innervation of 5-HT fibers to ChAT-positive motoneurons below the injury, and the increased VGlut2 expression suggests an enhanced excitatory synaptic activity. Overall, sustained activation of rat NPC post-transplantation offers a promising strategy for improved locomotor recovery following SCI.

PMID:40734274 | DOI:10.1016/j.ymthe.2025.07.041

Carbohydr Polym. 2025 Oct 15;366:123840. doi: 10.1016/j.carbpol.2025.123840. Epub 2025 Jun 6.

ABSTRACT

Polymer-based nanoparticle systems are gaining increasing attention in drug delivery due to their stability, biocompatibility, and controlled release capabilities. Understanding the self-assembly behavior of polysaccharides is crucial for designing effective nanocarriers, yet the conditions governing their organization remain poorly explored. In this study, we employed a combined in silico and in vitro approach to investigate the self-assembly mechanisms of levan and leverage this knowledge to develop a surfactant-free, bioinspired drug delivery system. Molecular simulations revealed that self-assembly is strongly influenced by pH, with alkaline conditions promoting compact, organized structures and acidic conditions leading to disordered arrangements. Guided by these findings, levan nanoparticles were synthesized both with and without the addition of the commonly used non-ionic surfactants Pluronic F-127 and Tween-80 and under optimal conditions, surfactant-free formulations demonstrated high encapsulation efficiency (∼80-92 %), enhanced stability, and controlled release of oleuropein (OLE), a bioactive polyphenol with poor gastrointestinal bioavailability. In vitro release studies demonstrated sustained OLE delivery over 24 h, with diffusion-controlled kinetics in intestinal conditions. Antioxidant activity assays confirmed that OLE retained its radical-scavenging properties post-encapsulation. Furthermore, cytocompatibility tests using fibroblast and colon cancer cell lines demonstrated that levan nanoparticles were non-toxic and supported cell viability.

PMID:40733757 | DOI:10.1016/j.carbpol.2025.123840

Vaccines (Basel). 2025 Jul 13;13(7):750. doi: 10.3390/vaccines13070750.

ABSTRACT

Background: Hemodialysis patients, due to impaired kidney function and compromised immune responses, face increased risks from SARS-CoV-2. Anti-nucleocapsid IgG (anti-IgG N) antibodies are a commonly used marker to assess prior infection in the general population; however, their efficacy for hemodialysis patients remains unclear. Methods: A retrospective study of 361 hemodialysis patients evaluated anti-IgG N antibodies for detecting prior SARS-CoV-2 infection. Antibody levels were measured using a chemiluminescence immunoassay (CLIA) over the four time points. Boxplots illustrated antibody distribution across sampling stages and infection status. Logistic regression and receiver operating characteristic (ROC) curve analysis determined diagnostic accuracy, sensitivity, specificity, and optimal cutoff values. Results: Among the 361 hemodialysis patients, 36 (10.0%) had SARS-CoV-2 infection. Sex distribution showed a trend toward significance (p = 0.05). Boxplot analysis showed that anti-IgG N levels remained low in non-infected patients but increased in infected patients, peaking at the third sampling. Anti-IgG N demonstrated high diagnostic accuracy (AUC: 0.973-0.865) but declined over time (p = 0.00525). The optimal cutoff at C1 was 0.01 AU/mL (sensitivity 1.00, specificity 0.94). Adjusted models had lower predictive value. Conclusions: Anti-IgG N antibodies showed high diagnostic accuracy for detecting prior SARS-CoV-2 infection in hemodialysis patients, though performance declined over time. These findings highlight the need for tailored diagnostic strategies in this vulnerable population.

PMID:40733727 | DOI:10.3390/vaccines13070750

Plants (Basel). 2025 Jul 14;14(14):2176. doi: 10.3390/plants14142176.

ABSTRACT

Bulgarian botanical gardens harbor more than 3600 plant species from across the world. Some of them are well-known plants widely used by humans, others are underutilized crops or little-known exotic species. The latter group constitutes a rich reservoir of plant resources whose potential to bring benefits to society is still untapped. The aim of this review is to describe the diversity of species and their potentially valuable secondary metabolites in three of the largest Bulgarian botanical gardens, with a focus on underutilized crops and medicinal plants that are typical of Bulgaria. With this, we aim to pave the way for future research on the most promising of these plants. The report includes currently available ethnobotanical data on the properties and composition of their bioactive components, known culinary or therapeutic uses, and nutritional profiles. We also outline the vast potential of these plants in providing healthy diets, as well as for performing future groundbreaking biomedical research. Finally, we present the approach that will be used to screen extracts from these plants for biological activity.

PMID:40733413 | DOI:10.3390/plants14142176

Molecules. 2025 Jul 11;30(14):2941. doi: 10.3390/molecules30142941.

ABSTRACT

We present a detailed examination of the absorption coefficients in the THz region for different water models using different types of potentials: the non-polarizable SPC/E, the Drude-polarizable SWM4-NDP and OPC3-pol, IPOL-0.13 and the multipole AMOEBA14 water. The primary focus is on understanding the interplay between permanent and induced dipole moments and their influence on the THz spectrum. Although the induced dipoles strongly contribute to the peak at 200 cm-1, merely increasing the induced dipole moments does not improve the agreement with experiments. We aim to investigate the behavior of the intensity at 200 cm-1 depending on the water model. Furthermore, we dissect the THz spectra of the water models into distinct contributions to gain more insight into the inter- and intramolecular interactions. Intermolecular interactions significantly contribute to the low-frequency peak, while the peak observed at 600 cm-1 can be adequately attributed to intramolecular dipole-dipole interactions.

PMID:40733210 | DOI:10.3390/molecules30142941

Nutrients. 2025 Jul 17;17(14):2348. doi: 10.3390/nu17142348.

ABSTRACT

Background/Objectives: Childhood stunting remains a critical public health issue in low- and middle-income countries. Despite Malaysia's economic growth, there is limited large-scale evidence on the determinants of stunting among children from infancy to primary school age. This cross-sectional study, part of South East Asian Nutrition Surveys II (SEANUTS II), aimed to determine sociodemographic and environmental risk factors for stunting among 2989 children aged 0.5-12 years. Methods: Children were recruited from four regions in Peninsular Malaysia (Central, East Coast, 2022-2030Northern, Southern). Standing height or recumbent length was measured, and stunting was classified based on WHO criteria (height-for-age Z-score below -2 standard deviations). Parents reported information on socioeconomic status, sanitation facilities, and hygiene practices. Multivariate binary logistic regression was used to determine the determinants of stunting. Results: Stunting prevalence was 8.9%, with infants (aOR = 2.92, 95%CI:1.14-7.52) and young children (aOR = 2.92, 95%CI:1.80-4.76) having higher odds than school-aged children. Key biological predictors included low birth weight (aOR = 2.41; 95%CI:1.40-4.13) and maternal height <150 cm (aOR = 2.24; 95%CI:1.36-3.70). Chinese (aOR = 0.56; 95%CI:0.35-0.88) and Indian children (aOR = 0.16; 95%CI:0.05-0.52) had a lower risk of stunting compared to Malays. Conclusions: This study highlights the ongoing challenge of childhood stunting in Malaysia, with age, birth weight, ethnicity, and maternal height identified as key determinants. These findings call for early identification of at-risk households and targeted support, especially through education and financial aid to foster healthy child growth.

PMID:40732975 | DOI:10.3390/nu17142348

Microorganisms. 2025 Jul 9;13(7):1622. doi: 10.3390/microorganisms13071622.

ABSTRACT

Verticillium wilt, caused by Verticillium dahliae, poses a significant threat to olive trees (Olea europaea L.). The isolation of endophytic Streptomyces strains from olive roots has led to the discovery of several strains showing strong antifungal activity against V. dahliae, as demonstrated through in vitro and small-scale soil experiments. Molecular analyses confirmed that strain OE54 belongs to Streptomyces iranensis. The main antifungal compound identified in this strain was rapamycin. Rapamycin displayed potent antifungal effects, notably inhibiting conidiospore germination (IC50 = 87.36 μg/mL) and the hyphal growth of V. dahliae, with a minimum inhibitory concentration (MIC50) of 3.91 ng/mL. Additionally, a second rapamycin-producing strain, OE57T, was isolated. Phenotypic and genotypic analyses indicated that OE57T represents a new species, which is proposed to be named Streptomyces lacaronensis sp. nov., with OE57T designated as the type strain (=DSM 118741T; CECT 31164T). The discovery of two endophytic rapamycin-producing Streptomyces strains residing within olive roots is especially notable, given the rarity of rapamycin production among microorganisms. These findings highlight the potential of rapamycin-producing Streptomyces strains in developing biofertilizers to manage V. dahliae and reduce the impact of Verticillium wilt on olive trees and other crops.

PMID:40732131 | DOI:10.3390/microorganisms13071622

Genome Biol. 2025 Jul 29;26(1):228. doi: 10.1186/s13059-025-03673-9.

ABSTRACT

Standardized analysis pipelines contribute to making data bioinformatics research compliant with the paradigm of Findability, Accessibility, Interoperability, and Reusability (FAIR), and facilitate collaboration. Nextflow and Snakemake, two popular command-line solutions, are increasingly adopted by users, complementing GUI-based platforms such as Galaxy. We report recent developments of the nf-core framework with the new Nextflow Domain-Specific Language (DSL2). An extensive library of modules and subworkflows enables research communities to adopt common standards progressively, as resources and needs allow. We present an overview of some of the research communities built around nf-core and showcase its adoption by six EuroFAANG farmed animal research consortia.

PMID:40731283 | DOI:10.1186/s13059-025-03673-9

Alzheimers Dement. 2025 Aug;21(8):e70519. doi: 10.1002/alz.70519.

ABSTRACT

INTRODUCTION: Mitochondrial dysfunction is implicated in Alzheimer's disease (AD), but whether it drives AD-associated changes is unclear. We assessed transcriptomic alterations in the brains of Ndufs4-/- mice, a model of mitochondrial complex I (mtCI) deficiency, and evaluated the therapeutic effects of the neuroprotective mtCI inhibitor CP2.

METHODS: Cortico-hippocampal tissue from Ndufs4-/- and wild-type mice was subjected to transcriptomic analysis, followed by cross-species comparisons to human late-onset AD and familial AD mouse datasets.

RESULTS: Knockout of Ndufs4-mediated mtCI deficiency disrupted mitochondrial homeostasis, energy metabolism, and synaptic gene expression, recapitulating transcriptomic signatures of AD. CP2 treatment partially reversed these changes, with female Ndufs4-/- mice showing greater compensatory adaptations and treatment responses.

DISCUSSION: Loss of mtCI activity alone is sufficient to induce AD-like molecular changes in the brain, independent of amyloid beta or phosphorylated tau. CP2-mediated rescue highlights the potential of targeting mitochondria as a therapeutic strategy for AD. Sex-specific responses suggest important considerations for personalized therapeutics.

HIGHLIGHTS: Activity of mitochondrial complex I (mtCI) affects broad mitochondrial and neuronal transcriptional networks. A reduction of mtCI activity is sufficient to induce transcriptomic changes reminiscent of those observed in late-onset Alsheimer's disease (AD) patients and familial mouse models of AD. Pharmacological targeting of mtCI mediates neuroprotective signaling. Male and female mice have differential responses to the loss of mtCI activity and to the mitochondria-targeted therapeutics. Mitochondria play a key role in AD development and treatment.

PMID:40731203 | DOI:10.1002/alz.70519

Nat Microbiol. 2025 Jul 29. doi: 10.1038/s41564-025-02070-z. Online ahead of print.

ABSTRACT

The global surge in antimicrobial resistance presents a critical threat to public health, emphasizing the urgent need for the development of new and more effective bacterial vaccines. Since the success of mRNA vaccines during the COVID-19 pandemic, this vaccine strategy has rapidly advanced, with most efforts focused on cancer immunotherapy and targeting viral pathogens. Recently, mRNA vaccines have entered the early phases of clinical development for bacterial diseases. However, bacteria present greater biological complexity compared with viruses, posing additional challenges for vaccine design, such as antigen selection, immune response and mRNA construct design. Here, we discuss critical aspects in the development of bacterial mRNA vaccines, from antigen selection to construct design. We also highlight the current preclinical landscape and discuss remaining translational challenges and future potential for mRNA vaccines against bacterial infections.

PMID:40730911 | DOI:10.1038/s41564-025-02070-z

Nat Commun. 2025 Jul 29;16(1):6948. doi: 10.1038/s41467-025-62066-5.

ABSTRACT

Pre- and post-transcriptional mechanisms, including alternative promoters, termination signals, and splicing, play essential roles in diversifying protein output by generating distinct RNA and protein isoforms. Two major challenges in characterizing the cellular function of alternative isoforms are the lack of experimental methods to specifically and efficiently modulate isoform expression and computational tools for complex experimental design and analysis. To address these gaps, we develop and methodically test an isoform-specific knockdown strategy which pairs the RNA-targeting CRISPR/Cas13d system with guide RNAs that span exon-exon junctions. In parallel, we provide computational tools for experimental design and analysis. In this study, we demonstrate that junction-targeting achieves robust and isoform-specific RNA knockdown across diverse alternative isoform events, genes, and cell types.

PMID:40730819 | DOI:10.1038/s41467-025-62066-5

Mol Divers. 2025 Jul 29. doi: 10.1007/s11030-025-11300-9. Online ahead of print.

ABSTRACT

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a critical global health challenge due to rising drug resistance and the pathogen's ability to persist in hostile host environments. Identifying novel molecular targets that underlie Mtb's unique survival mechanisms is essential for developing more effective therapies. In this study, we developed an integrative computational pipeline combining genome-scale metabolic modeling, flux balance analysis (FBA), comparative genomics, and network-based prioritization to uncover metabolic vulnerabilities specific to Mtb. Comparative analysis with the reductively evolved Mycobacterium leprae revealed significant differences in pathways involved in pantothenate biosynthesis (PanB), peptidoglycan synthesis (GlmU), and branched-chain amino acid metabolism (IlvN). These targets were prioritized based on gene essentiality, dormancy-associated expression, druggability, and absence of human homologs to maximize therapeutic selectivity. Molecular docking, followed by MM-GBSA binding free energy calculations, identified high-affinity ligands from LifeChemicals and ChEMBL libraries interacting strongly with active-site residues. Molecular dynamics simulations were performed to further validate target engagement and ligand retention, revealing stable conformational behavior and persistent protein-ligand interactions across 300 ns. Similarly, metabolite flux analysis and pathway enrichment highlighted adaptive rewiring in glycine, serine, pyruvate, and nitrogen metabolism, reflecting Mtb's persistence strategies under host-imposed stress. This study provides a robust, generalizable pipeline for pathogen-specific drug target and ligand discovery and supports the rational development of new therapies against drug-resistant tuberculosis.

PMID:40730708 | DOI:10.1007/s11030-025-11300-9

Cell Rep Methods. 2025 Jul 23:101117. doi: 10.1016/j.crmeth.2025.101117. Online ahead of print.

ABSTRACT

This paper reports a 3D-printed plug as a meso-scale interface solution that minimizes sample loss and enhances cell usage efficiency, seamlessly connecting microfluidic systems to conventional well plates. The plug concentrates cells near the region of interest for chemotaxis, reducing cell number requirements and featuring tapered structures for efficient manual or robotic liquid handling. Comprehensive testing showed that the plug increased cell usage efficiency in single-cell migration assays by 8-fold, maintaining accuracy and sensitivity. We also extended our approach to neuron axon guidance assays, where limited cell availability is a constraint, and observed substantial improvements in assay outcomes. This integration of 3D printing with microfluidics establishes low-loss interfaces for precious samples, advancing the capabilities of microfluidic technology.

PMID:40730156 | DOI:10.1016/j.crmeth.2025.101117

Plant Physiol Biochem. 2025 Jul 25;228:110298. doi: 10.1016/j.plaphy.2025.110298. Online ahead of print.

ABSTRACT

Water stress challenges global crop productivity, particularly for perennial species such as grapevines, where effective water management is crucial for berry quality and yield. Aquaporins, a family of water channel proteins, play a key role in regulating water transport within plant cells, affecting water uptake and redistribution. Although the transcriptional response of aquaporin genes to water stress in grapevines has been documented, their translational regulation remains less explored. This study investigates the transcriptional and translational dynamics of three Plasma Membrane Intrinsic Proteins and three Tonoplast Intrinsic Proteins in leaves and roots of a grafted 'Pinot Noir' on 'Kober 5BB' rootstock during water deficit conditions and recovery. Aquaporin translation analyzed by polysome profiling and co-sedimentation analysis of their transcripts highlighted that water stress had a general negative effect, although significant only for VviTIP1-3. Conversely, recovery measured at 6 h after rewatering was characterized by a boost of translation reactivation for all but one aquaporins. Transcriptional profiling of the same aquaporins revealed significant down-regulation at prolonged stress in roots, highlighting the contribution of aquaporins to osmoregulation and drought tolerance. Moreover, transcriptional modulation resembles a long-term adaptative response to limit water loss. In the leaf, only two specific genes, VviPIP2-5 and VviTIP2-1, were modulated during water deficit and even more during recovery and positively correlated with stomatal conductance and leaf water potential. They represent important regulators of water homeostasis and good candidates for breeding programs. This study uncovered an additional level of aquaporin post-transcriptional control finely tuning vines to changing external conditions.

PMID:40729951 | DOI:10.1016/j.plaphy.2025.110298

J Hazard Mater. 2025 Jul 26;496:139367. doi: 10.1016/j.jhazmat.2025.139367. Online ahead of print.

ABSTRACT

Abelmoschus manihot is a promising cadmium (Cd) hyperaccumulator for phytoremediation, but its endophytic bacterial community diversity and the bioremediation potential of its culturable endophytes remain underexplored. In this study, we employed high-throughput sequencing technology to comprehensively analyze the diversity, structure, and composition of endophytic bacteria in A. manihot under different levels of Cd stress. Our results showed that the root endosphere community was more strongly affected by Cd stress than the aboveground endosphere. Cd exposure markedly reduced bacterial diversity and altered the composition of the dominant genera in the root endosphere across different Cd concentrations. Network analysis revealed that Cd stress increased microbial connectivity in root communities while reducing network complexity in aboveground communities, indicating tissue-specific microbial adaptation. In the microbial networks, keystone taxa, primarily from the phyla Proteobacteria and Firmicutes, played essential roles in microbial interactions. Functional profiling through PICRUSt2 prediction revealed significant differences in the metabolic pathways of endophytic bacteria between plant compartments. Interestingly, pathways associated with transcription factors, quorum sensing, and glyoxylate and dicarboxylate metabolism were upregulated in both the root and leaf microbiomes under Cd stress. Furthermore, a core microbiome of 33 amplicon sequence variants (ASVs), dominated by Proteobacteria and Firmicutes, was consistently present across both root and aboveground tissues. 41 Cd-resistant endophytic strains were further isolated, among which the Bacillus strain BL-61 demonstrated strong potential for promoting plant growth and Cd accumulation. These findings underscore the critical roles of endophytic bacteria in hyperaccumulator adaptation to heavy metal stress and provide a foundation for developing microbe-assisted phytoremediation strategies.

PMID:40729874 | DOI:10.1016/j.jhazmat.2025.139367

J Reprod Immunol. 2025 Jul 18;171:104621. doi: 10.1016/j.jri.2025.104621. Online ahead of print.

ABSTRACT

Cellular senescence is a well-established biological phenomenon in eukaryotes. It involves DNA damage, telomere shortening, a senescence-associated secretory phenotype (SASP), and the inability of cells to replicate. It is associated with ageing, and also with oxidative stress. Given the importance of oxidative stress in pre-eclampsia, there is considerable evidence, that we review, that senescence plays an important role in both normal placental development and in the development of both early- and late-term pre-eclampsia. Autophagy is capable of delaying or even reversing the development of senescence, and certain small molecules such as sulforaphane and spermidine can stimulate autophagy, including via the redox-sensitive transcription factor Nrf2. Ergothioneine is a thiohistidine antioxidant that is protective against a variety of cardiovascular and other diseases. Ergothioneine also interacts with Nrf2, and pre-eclampsia occurs far less frequently in individuals with higher plasma ergothioneine levels. Together, these elements provide a self-consistent, molecular and systems biology explanation for at least one mechanism by which ergothioneine may be protective against pre-eclampsia.

PMID:40729821 | DOI:10.1016/j.jri.2025.104621

Plant Biotechnol J. 2025 Jul 29. doi: 10.1111/pbi.70282. Online ahead of print.

ABSTRACT

Chitin triggers localised and systemic plant immune responses, making it a promising treatment for sustainable disease resistance. However, the precise molecular mechanisms underlying chitin-induced systemic effects in plants remain unknown. In this study, we investigated the effects of soil amendment with crab chitin flakes (hereafter chitin) on pattern-triggered immunity (PTI) and systemic disease resistance in various plant species. We found that soil amendment with chitin potentiates PTI and disease resistance against the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 in lettuce, tomato and Arabidopsis as well as against the fungal pathogen Blumeria graminis f. sp. tritici (Bgt), which causes powdery mildew in wheat. Using micrografting in Arabidopsis, we demonstrated that this systemic effect is dependent on active chitin perception in the roots. We also showed that induced systemic resistance (ISR) and pattern-recognition receptors (PRRs)/coreceptors, but not systemic acquired resistance (SAR), are involved in the systemic effects triggered by chitin soil amendment. These systemic effects correlated with the transcriptional upregulation of key PTI regulators in distal leaves upon chitin soil amendment. Notably, chitin-triggered systemic immunity was independent of microbes present in soil or chitin flakes. Together, these findings contribute to a better understanding of chitin-triggered systemic immunity, from active chitin perception in roots to the potentiation of PTI in the leaves, ultimately priming plants to mount enhanced defence responses against pathogen attacks. Our study provides valuable insights into the molecular mechanisms of chitin soil amendment and resulting induced immunity and highlights its potential use for sustainable crop protection strategies.

PMID:40729549 | DOI:10.1111/pbi.70282

Cell Prolif. 2025 Jul 29:e70103. doi: 10.1111/cpr.70103. Online ahead of print.

ABSTRACT

Differences in gene expression, which arise from divergence in cis-regulatory elements or alterations in transcription factors (TFs) binding specificity, are one of the most important causes of phenotypic diversity during evolution. On one hand, changes in the cis-elements located in the vicinity of target genes affect TF binding and/or local chromatin environment, thereby modulating gene expression in cis. On the other hand, alterations in trans-factors influence the expression of their target genes in a more pleiotropic fashion. Although the evolution of amino acid sequences is much slower than that of non-coding regulatory elements, particularly for the TF DNA binding domains (DBDs), it is still possible that changes in TF-DBD might have the potential to drive large phenotypic changes if the resulting effects have a net positive effect on the organism's fitness. If so, species-specific changes in TF-DBD might be positively selected. So far, however, this possibility has been largely unexplored. By protein sequence analysis, we observed high sequence conservation in the DBD of the TF caudal-type homeobox 2 across many vertebrates, whereas three amino acid changes were exclusively found in mouse Cdx2 (mCdx2), suggesting potential positive selection in the mouse lineage. Multi-omics analyses were then carried out to investigate the effects of these changes. Surprisingly, there were no significant functional differences between mCdx2 and its rat homologue (rCdx2), and none of the three amino acid changes had any impact on its function. Finally, we used rat-mouse allodiploid embryonic stem cells to study the cis effects of Cdx2-mediated gene regulation between the two rodents. Interestingly, whereas Cdx2 binding is largely divergent between mouse and rat, the transcriptional effect induced by Cdx2 is conserved to a much larger extent. There were no significant functional differences between mCdx2 and its rat homologue (rCdx2), and none of the three amino acid changes had any impact on its function. Moreover, Cdx2 binding is largely divergent between mouse and rat; the transcriptional effect induced by Cdx2 is conserved to a much larger extent.

PMID:40729530 | DOI:10.1111/cpr.70103

Plant Biotechnol J. 2025 Jul 29. doi: 10.1111/pbi.70279. Online ahead of print.

ABSTRACT

Botrytis cinerea (Bc) is a major pathogen of cultivated grapevine (Vitis vinifera L.), with cell wall (CW) remodelling playing a critical role in fungal colonisation. CW-modifying enzymes, particularly pectin methylesterases (PMEs), produced by both host and pathogen, influence CW integrity and the outcome of infection. To explore the role of CW composition and remodelling in grapevine's response to Bc, we inoculated three genotypes with varying susceptibility at full flowering. Biochemical analysis of flowers and ripe berry skins revealed that the tolerant genotype exhibited significantly higher PME activity postinfection compared with the susceptible ones. Unbiased transcriptome analysis of infected flower tissues showed a more intense transcriptional response in the susceptible genotype, suggesting an ultimately ineffective attempt to restrict fungus spread. Expression profiling of 62 PME genes in this data set and public Bc-infected berry transcriptomes identified PME10 as the most strongly induced gene upon infection. PME10 knockout mutants displayed reduced PME activity and heightened susceptibility, while overexpression lines showed enhanced PME activity and reduced disease symptoms. Gene co-expression network analysis highlighted WRKY03, a defence-related transcription factor, as a putative regulator of PME10. DAP-seq, DAP-qPCR and dual luciferase assays confirmed direct binding and activation of the PME10 promoter by WRKY03. Altogether, this study demonstrates that PME10 is a functional PME contributing to grapevine immunity against B. cinerea, establishing it as a key component of the grapevine defence machinery against fungal pathogens.

PMID:40729521 | DOI:10.1111/pbi.70279

PLoS Biol. 2025 Jul 29;23(7):e3003287. doi: 10.1371/journal.pbio.3003287. eCollection 2025 Jul.

ABSTRACT

Metabolic cross-feeding networks are central to shaping microbial community dynamics in environments ranging from the rhizosphere, gut, and marine carbon cycling. Yet cross-feeding has predominantly been viewed by examining exchanged small metabolites. In contrast, the role of extracellular polymeric substance (EPS)-a complex mixture of proteins, polysaccharides, DNA, and humic-like compounds-in cross-feeding remains poorly understood, mainly due to technical challenges in measuring their secretion relative to small metabolites. Using chitin-degrading microbes as a model system, we used a bicarbonate-buffered bioreactor coupled with elemental analysis, which allowed us to quantify both EPS and small metabolite secretion. This revealed that ~25% of carbon exuded by a chitin degrader is in the form of EPS. EPS was produced at similar levels across marine chitin-degrading isolates and seawater communities, underscoring its importance relative to small metabolites. Notably, different sources of EPS were found to select for distinct and diverse microbial communities. Combining in vitro enzyme assays and untargeted metabolomics, we show that EPS undergoes sequential degradation-from large oligomers to smaller, broadly accessible monomers. This sequential breakdown creates a temporal succession of metabolic niches, potentially fueling a shift from specialist species degrading complex substrates to a more diverse community of generalists using simpler monomers. By identifying EPS as a major and dynamic contributor to cross-feeding networks, our findings reveal a hidden layer of complexity in how microbial communities assemble and function across ecosystems.

PMID:40729313 | DOI:10.1371/journal.pbio.3003287