Nat Methods. 2025 May 12. doi: 10.1038/s41592-025-02660-z. Online ahead of print.

ABSTRACT

Despite being information rich, the vast majority of untargeted mass spectrometry data are underutilized; most analytes are not used for downstream interpretation or reanalysis after publication. The inability to dive into these rich raw mass spectrometry datasets is due to the limited flexibility and scalability of existing software tools. Here we introduce a new language, the Mass Spectrometry Query Language (MassQL), and an accompanying software ecosystem that addresses these issues by enabling the community to directly query mass spectrometry data with an expressive set of user-defined mass spectrometry patterns. Illustrated by real-world examples, MassQL provides a data-driven definition of chemical diversity by enabling the reanalysis of all public untargeted metabolomics data, empowering scientists across many disciplines to make new discoveries. MassQL has been widely implemented in multiple open-source and commercial mass spectrometry analysis tools, which enhances the ability, interoperability and reproducibility of mining of mass spectrometry data for the research community.

PMID:40355727 | DOI:10.1038/s41592-025-02660-z

Nat Plants. 2025 May 12. doi: 10.1038/s41477-025-01996-w. Online ahead of print.

ABSTRACT

Agrobacterium pathogenesis, which involves transferring T-DNA into plant cells, is the cornerstone of plant genetic engineering. As the applications that rely on Agrobacterium increase in sophistication, it becomes critical to achieve a quantitative and predictive understanding of T-DNA expression at the level of single plant cells. Here we examine if a classic Poisson model of interactions between pathogens and host cells holds true for Agrobacterium infecting Nicotiana benthamiana. Systematically challenging this model revealed antagonistic and synergistic density-dependent interactions between bacteria that do not require quorum sensing. Using various approaches, we studied the molecular basis of these interactions. To overcome the engineering constraints imposed by antagonism, we created a dual binary vector system termed 'BiBi', which can improve the efficiency of a reconstituted complex metabolic pathway in a predictive fashion. Our findings illustrate how combining theoretical models with quantitative experiments can reveal new principles of bacterial pathogenesis, impacting both fundamental and applied plant biology.

PMID:40355701 | DOI:10.1038/s41477-025-01996-w

Nat Rev Genet. 2025 May 12. doi: 10.1038/s41576-025-00853-y. Online ahead of print.

NO ABSTRACT

PMID:40355601 | DOI:10.1038/s41576-025-00853-y

Nat Biotechnol. 2025 May 12. doi: 10.1038/s41587-025-02697-7. Online ahead of print.

NO ABSTRACT

PMID:40355567 | DOI:10.1038/s41587-025-02697-7

Proc Natl Acad Sci U S A. 2025 May 20;122(20):e2412218122. doi: 10.1073/pnas.2412218122. Epub 2025 May 12.

ABSTRACT

MEX-5 regulates the formation and dissolution of P granules in Caenorhabditis elegans embryos, yet the thermodynamic basis of its activity remains unclear. Here, using a time-resolved in vitro reconstitution system, we show that MEX-5 dissolves preassembled liquid-like PGL-3/RNA condensates by altering RNA availability and shifting the phase boundary. We develop a microfluidic assay to systematically analyze how MEX-5 influences phase separation. By measuring the contribution of PGL-3 to phase separation, we show that MEX-5 reduces the free energy of PGL-3, shifting the equilibrium toward dissolution. Our findings provide a quantitative framework for understanding how RNA-binding proteins modulate condensate stability and demonstrate the power of microfluidics in precisely mapping phase transitions.

PMID:40354522 | DOI:10.1073/pnas.2412218122

PLoS Comput Biol. 2025 May 12;21(5):e1013076. doi: 10.1371/journal.pcbi.1013076. Online ahead of print.

ABSTRACT

Epithelial-mesenchymal transition (EMT) plays an essential role in embryonic development, wound healing, and tumor progression. Partial EMT states have been linked to metastatic dissemination and drug resistance. Several interconnected feedback loops at the RNA and protein levels control the transition between different cellular states. Using a combination of mathematical modeling and experimental analyses in the TGFβ-responsive breast epithelial MCF10A cell model, we identify a central role for the tumor suppressor protein Deleted in Liver Cancer 1 (DLC1) during EMT. By extending a previous model of EMT comprising key transcription factors and microRNAs, our work shows that DLC1 acts as a positive regulator of TGFβ-driven EMT, mainly by promoting SNAIL1 expression. Our model predictions indicate that DLC1 loss impairs EMT progression. Experimental analyses confirm this prediction and reveal the acquisition of a partial EMT phenotype in DLC1-depleted cells. Furthermore, our model results indicate a possible EMT reversion to partial or epithelial states upon DLC1 loss in MCF10A cells induced toward mesenchymal phenotypes. The increased EMT plasticity of cells lacking DLC1 may explain its importance as a tumor suppressor.

PMID:40354489 | DOI:10.1371/journal.pcbi.1013076

PLoS Comput Biol. 2025 May 12;21(5):e1013098. doi: 10.1371/journal.pcbi.1013098. Online ahead of print.

ABSTRACT

Uncertainty quantification (UQ) is the process of systematically determining and characterizing the degree of confidence in computational model predictions. In systems biology, and particularly with dynamic models, UQ is critical due to the nonlinearities and parameter sensitivities that influence the behavior of complex biological systems. Addressing these issues through robust UQ enables a deeper understanding of system dynamics and more reliable extrapolation beyond observed conditions. Many state-of-the-art UQ approaches in this field are grounded in Bayesian statistical methods. While these frameworks naturally incorporate uncertainty quantification, they often require the specification of parameter distributions as priors and may impose parametric assumptions that do not always reflect biological reality. Additionally, Bayesian methods can be computationally expensive, posing significant challenges when dealing with large-scale models and seeking rapid, reliable uncertainty calibration. As an alternative, we propose using conformal predictions methods and introduce two novel algorithms designed for dynamic biological systems. These approaches can provide non-asymptotic guarantees, improving robustness and scalability across various applications, even when the predictive models are misspecified. Through several illustrative scenarios, we demonstrate that these conformal algorithms can serve as powerful complements-or even alternatives-to conventional Bayesian methods, delivering effective uncertainty quantification for predictive tasks in systems biology.

PMID:40354480 | DOI:10.1371/journal.pcbi.1013098

Integr Comp Biol. 2025 May 12:icaf036. doi: 10.1093/icb/icaf036. Online ahead of print.

ABSTRACT

Diverse vertebrate species utilize hibernation as an energy-management strategy to survive long-term resource scarcity. Many hibernating and non-hibernating species employ food hoarding as a behavioral mechanism for storing surplus energy. Although the thirteen-lined ground squirrel (Ictidomys tridecemlineatus, 13LGS) relies mainly on body fat as fuel during hibernation, they also hoard food under natural and captive conditions. We tested the hypothesis that 13LGS individual variation in facultative hoarding behavior is driven by internal physiology, including body mass, sex, anxiety, and baseline stress. We recorded food hoard composition and body weight biweekly in summer active squirrels, subjected them to the open-field test (OFT) to measure state anxiety, and quantified fecal corticosterone (CORT) levels to measure baseline stress. We found that hoard sizes increased significantly across the summer, peaking at the end of June when body weight was still linearly increasing. Individual variation accounted for 10-20% of total variation in hoarding patterns. We observed a significant effect of sex on hoard size and composition, with males hoarding more than females. Contrary to our predictions, there was no relationship between hoarding and anxiety-like behavior in the OFT, and non-hoarders had significantly higher fecal CORT than hoarders. Together, our results suggest that time, sex, and baseline stress are significant factors that affect hoarding behavior, but body weight and anxiety-like behaviors are not. In the context of organismal systems biology, food hoarding is a redundant mechanism to fat storage that increases an organism's resilience against future resource scarcity and is likely regulated by dynamic interactions between multiple brain-body networks.

PMID:40353766 | DOI:10.1093/icb/icaf036

mBio. 2025 May 12:e0074925. doi: 10.1128/mbio.00749-25. Online ahead of print.

ABSTRACT

In the Arctic, phytoplankton blooms are recurring phenomena occurring during the spring-summer seasons and influenced by the strong polar seasonality. Bloom dynamics are affected by nutrient availability, especially nitrogen, which is the main limiting nutrient in the Arctic. This study aimed to investigate the changes in an Arctic microbial community using omics approaches during a phytoplankton bloom focusing on the nitrogen cycle. Using metagenomic and metatranscriptomic samples from the Dease Strait (Canada) from March to July (2014), we reconstructed 176 metagenome-assembled genomes. Bacteria dominated the microbial community, although archaea reached up to 25% of metagenomic abundance in early spring, when Nitrososphaeria archaea actively expressed genes associated with ammonia oxidation to nitrite (amt, amo, nirK). The resulting nitrite was presumably further oxidized to nitrate by a Nitrospinota bacterium that highly expressed a nitrite oxidoreductase gene (nxr). Since May, the constant increase in chlorophyll a indicated the occurrence of a phytoplankton bloom, promoting the successive proliferation of different groups of chemoorganotrophic bacteria (Bacteroidota, Alphaproteobacteria, Gammaproteobacteria). These bacteria showed different strategies to obtain nitrogen, whether it be from organic or inorganic sources, according to the expression patterns of genes encoding transporters for nitrogen compounds. In contrast, during summer, the chemolithotrophic organisms thriving during winter reduced their relative abundance and the expression of their catabolic genes. Based on our functional analysis, we see a transition from a community where nitrogen-based chemolitotrophy plays a relevant role to a chemoorganotrophic community based on the carbohydrates released during the phytoplankton bloom, where different groups seem to specialize in different nitrogen sources.IMPORTANCEThe Arctic is one of the environments most affected by anthropogenic climate change. It is expected that the rise in temperature and change in ice cover will impact the marine microbial communities and the associated biogeochemical cycles. In this regard, nitrogen is the main nutrient limiting Arctic phytoplankton blooms. In this study, we combine genetic and expression data to study the nitrogen cycle at the community level over a time series covering from March to July. Our results indicate the importance of different taxa (from archaea to bacteria) and processes (from chemolithoautotrophy to incorporation of different nitrogen sources) in the cycling of nitrogen during this period. This study provides a baseline for future research that should include additional methodologies like biogeochemical analysis to fully understand the changes occurring on these communities due to global change.

PMID:40353658 | DOI:10.1128/mbio.00749-25

Faraday Discuss. 2025 May 12. doi: 10.1039/d4fd00202d. Online ahead of print.

ABSTRACT

We consider membranes as fluid deformable surfaces and allow for higher order geometric terms in the bending energy related to the Gaussian curvature squared and the mean curvature minus the spontaneous curvature to the fourth power. The evolution equations are derived and numerically solved using surface finite elements. The two higher order geometric terms have different effects. While the Gaussian curvature squared term has a tendency to stabilize tubes and enhance the evolution towards equilibrium shapes, thereby facilitating rapid shape changes, the mean curvature minus the spontaneous curvature to the fourth power destabilizes tubes and leads to qualitatively different equilibrium shapes but also enhances the evolution. This is demonstrated in axisymmetric settings and fully three-dimensional simulations. We therefore postulate that not only surface viscosity but also higher order geometric terms in the bending energy contribute to rapid shape changes which are relevant for morphological changes of cells.

PMID:40353330 | DOI:10.1039/d4fd00202d

Front Pediatr. 2025 Apr 25;13:1567091. doi: 10.3389/fped.2025.1567091. eCollection 2025.

ABSTRACT

Bronchopulmonary dysplasia (BPD) is a multifactorial chronic lung disease of premature neonates. BPD development depends on prenatal and postnatal factors that induce inflammation, altering alveolar growth and pulmonary vascular development. Animal models are essential to investigate the precise molecular pathways leading to BPD. The preterm rabbit combines many advantages of small (e.g., rodents) and large BPD models (e.g., preterm lambs and baboons). Preterm rabbits display mild-to-moderate respiratory distress at delivery, which, along with continuous exposure to hyperoxia (95% O2), leads to functional and morphological lung changes resembling a BPD-like phenotype. Nevertheless, the molecular pathways leading to the BPD-like phenotype remain poorly understood. Here, we aimed to characterize the longitudinal gene expression in the lungs of preterm rabbits exposed to 95% O2, on postnatal days 3, 5, and 7. Histological analyses confirmed extensive lung injury and reduced lung development after 7 days of hyperoxia. Longitudinal transcriptomic analysis revealed different expression patterns for several genes and pathways. Over time, extracellular matrix organization and angiogenesis were increasingly downregulated. Apoptosis, RNA processing, and inflammation showed the opposite trend. We also investigated the expression of representative genes of these pathways, whose signatures could aid in developing pharmacological treatments in the context of BPD.

PMID:40352610 | PMC:PMC12063497 | DOI:10.3389/fped.2025.1567091

Front Microbiol. 2025 Apr 25;16:1583746. doi: 10.3389/fmicb.2025.1583746. eCollection 2025.

ABSTRACT

Lignocellulose biomass is one of the most abundant resources for sustainable biofuels. However, scaling up the biomass-to-biofuels conversion process for widespread usage is still pending. One of the main bottlenecks is the high cost of enzymes used in key process of biomass degradation. Current research efforts are therefore targeted at creative solutions to improve the feasibility of lignocellulosic-degrading enzymes. One way is to engineer multi-enzyme complexes that mimic the bacterial cellulosomal system, known to increase degradation efficiency up to 50-fold when compared to freely-secreted enzymes. However, these designer cellulosomes are instable and less efficient than wild type cellulosomes. In this review, we aim to extensively analyze the current knowledge on the lignocellulosic-degrading enzymes through three aspects. We start by reviewing and comparing sets of enzymes in bacterial and fungal lignocellulose degradation. Next, we focus on the characteristics of cellulosomes in both systems and their feasibility to be engineered. Finally, we highlight three key strategies to enhance enzymatic lignocellulose degradation efficiency: discovering novel lignocellulolytic species and enzymes, bioengineering enzymes for improved thermostability, and structurally optimizing designer cellulosomes. We anticipate these insights to act as resources for the biomass community looking to elevate the usage of lignocellulose as biofuel.

PMID:40351319 | PMC:PMC12063362 | DOI:10.3389/fmicb.2025.1583746

ChemistryOpen. 2025 May 12:e2500004. doi: 10.1002/open.202500004. Online ahead of print.

ABSTRACT

Phlomis species (family Lamiaceae) are highly valued as food and herbal medicine. The present study is designed to investigate the chemical composition and antioxidant and enzyme inhibitory activities of extracts from P. fruticosa, P. herba-venti, and P. kurdica aerial parts. Different classes of metabolites, including phenolic acids, phenylethanoids, flavonoids, iridoids, organic acids, terpenes, and fatty acids, are identified in the three species, with methanol as the best solvent to recover bioactive compounds from the three species in addition to ethyl acetate for P. kurdica. Around 70% methanol extract of P. herba-venti exerts the best radical scavenging and ions-reducing properties, while its methanol extract exhibits the highest acetylcholinesterase inhibitory activity. The ethyl acetate extract of P. fruticosa displays the best chelating power, and its other polar extracts have the highest total antioxidant activity. Furthermore, molecular docking and molecular dynamics simulations have underscored the therapeutic potential of bioactive compounds, including isoverbascoside, samioside, forsythoside B, and hattushoside. In conclusion, the study indicates that these three Phlomis species are a rich source of bioactive molecules with possible therapeutic applications, and the selection of appropriate extraction solvents is crucial for the targeted biological activity.

PMID:40351016 | DOI:10.1002/open.202500004

J Dairy Sci. 2025 May 9:S0022-0302(25)00320-0. doi: 10.3168/jds.2025-26328. Online ahead of print.

ABSTRACT

We conducted a large GWAS of 11 health traits belonging to 3 trait complexes: (1) metabolic diseases, (2) infectious and noninfectious feet and claw disorders, and (3) udder-related traits in 100,809 to 180,217 German Holstein cows to investigate the genetic architecture and underlying biological mechanisms behind these complex traits. The GWAS identified 12,306 genome-wide significant variants across 10 traits. The new association signals were inspected with a Bayesian fine-mapping approach, leading to the discovery of 159 novel variants with high potential for causality. Variants were in known and novel regions for the traits studied, leading to a list of 53 novel candidate genes. Our study represents the largest whole-genome sequence GWAS for health traits so far, hence ensuring the power to detect meaningful variants, especially when enhanced with fine-mapping.

PMID:40349760 | DOI:10.3168/jds.2025-26328

J Pediatr (Rio J). 2025 May 8:S0021-7557(25)00078-6. doi: 10.1016/j.jped.2024.10.013. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of the investigation was to assess the potential mediating role of mental health in the association between cardiorespiratory fitness (CRF) and academic performance in European schoolchildren.

METHOD: The study followed a cross-sectional design. 507 schoolchildren (51.5 % girls, 7.4 ± 0.4 years) from 20 schools in five European countries were included in the analyses. Academic performance was assessed using school grades, mental health was assessed through the Strengths and Difficulties Questionnaire (SDQ) for parents, and CRF was estimated through the multistage 20-m shuttle run test. Linear regression and mediation analyses were conducted to test these hypotheses.

RESULTS: Mental health difficulties were associated with worse performance on academic indicators (β ranging from -0.121 to -0.324, p < 0.05). Further, mental health difficulties were associated with lower CRF (β ranging from -0.121 to -0.189, p < 0.05). Mediation analyses revealed that the association between CRF and academic performance indicators was partially mediated (from 8 % to 25 %) by mental health [except for conduct and peer problems (β ranging from -0.025 to -0.080, p > 0.05).

CONCLUSION: The present results highlight that mental health is a possible mediator in the association between CRF and academic performance. These findings might support the importance of improving CRF levels to reduce mental health difficulties with subsequent potential benefits on academic performance.

PMID:40349722 | DOI:10.1016/j.jped.2024.10.013

Curr Opin Struct Biol. 2025 May 10;93:103050. doi: 10.1016/j.sbi.2025.103050. Online ahead of print.

ABSTRACT

Reconstitution and direct extraction of membrane proteins using saposins is an emerging technique for solubilizing and stabilizing membrane proteins. The Salipro technology offers several advantages over traditional detergent solubilization, including a more native lipid environment, increased protein stability, and maintenance of functionality. This review covers recent studies that have used Salipros to characterize membrane proteins, as well as advances in direct extraction methods that have enabled the structural and functional characterization of a variety of targets.

PMID:40349676 | DOI:10.1016/j.sbi.2025.103050

Cell Rep. 2025 May 9;44(5):115680. doi: 10.1016/j.celrep.2025.115680. Online ahead of print.

ABSTRACT

Chromatin and DNA modifications mediate the transcriptional activity of lineage-specifying enhancers, but recent work challenges the dogma that joint chromatin accessibility and DNA demethylation are prerequisites for transcription. To understand this paradox, we established a highly resolved timeline of their dynamics during neural progenitor cell differentiation. We discovered that, while complete demethylation appears delayed relative to shorter-lived chromatin changes for thousands of enhancers, DNA demethylation actually initiates with 5-hydroxymethylation before appreciable accessibility and transcription factor occupancy is observed. The extended timeline of DNA demethylation creates temporal discordance appearing as heterogeneity in enhancer regulatory states. Few regions ever gain methylation, and resulting enhancer hypomethylation persists long after chromatin activities have dissipated. We demonstrate that the temporal methylation status of CpGs (mC/hmC/C) predicts past, present, and future chromatin accessibility using machine learning models. Thus, chromatin and DNA methylation collaborate on different timescales to shape short- and long-term enhancer regulation during cell fate specification.

PMID:40349339 | DOI:10.1016/j.celrep.2025.115680

ISME J. 2025 May 11:wraf093. doi: 10.1093/ismejo/wraf093. Online ahead of print.

ABSTRACT

Anthropogenic perturbations to the nitrogen cycle, primarily through use of synthetic fertilizers, is driving an unprecedented increase in the emission of nitrous oxide (N2O), a potent greenhouse gas and an ozone depleting substance, causing urgency in identifying the sources and sinks of N2O. Microbial denitrification is a primary contributor to biotic production of N2O in anoxic regions of soil, marine systems, and wastewater treatment facilities. Here, through comprehensive genome analysis, we show that pathway partitioning is a ubiquitous mechanism of complete denitrification within microbial communities. We have investigated mechanisms and consequences of process partitioning of denitrification through detailed physiological characterization and kinetic modeling of a synthetic community of Rhodanobacter thiooxydans FW510-R12 and Acidovorax sp. GW101-3H11. We have discovered that these two bacterial isolates, from a heavily nitrate (NO3-) contaminated superfund site, complete denitrification through the exchange of nitrite (NO2-) and nitric oxide (NO). The process partitioning of denitrification and other processes, including amino acid metabolism, contribute to increased cooperativity within this denitrifying community. We demonstrate that certain contexts, such as high NO3-, cause unbalanced growth of community members, due to differences in their substrate utilization kinetics. The altered growth characteristics of community members drives accumulation of toxic NO2-, which disrupts denitrification causing N2O off gassing.

PMID:40349173 | DOI:10.1093/ismejo/wraf093

Sci Rep. 2025 May 10;15(1):16310. doi: 10.1038/s41598-025-00763-3.

ABSTRACT

Medulloblastoma (MB) is the most common malignant pediatric brain tumor, accounting for approximately 20% of all childhood brain tumors. Despite recent advances, current treatments like surgery, radiation, and chemotherapy still lead to severe side effects and high morbidity. Limited knowledge exists regarding the regulatory mechanisms behind the MB transcriptional alterations in high-aggressive subgroups like Group 3 and Group 4, hindering the development of targeted therapies. Identifying key transcriptional regulators, known as master regulators (MRs), can elucidate the dysregulated pathways underlying MB progression and uncover potential treatment targets. In this study, we utilize primary MB gene expression samples to infer its regulatory network. Subsequently, we applied the Master Regulator Analysis identifying the transcription factors BHLHE41, RFX4, and NPAS3 as its main transcriptional regulators, showing tumor suppressor features. We also identified eight risk MRs highly associated with patient outcome: four regulators (MYC, REL, ZSCAN5 A, and ZFAT) with activities associated with poor prognosis, and four (PAX6, ARNT2, ZNF157, and HIVEP3) acting antagonistically, being associated with good outcome. Our results offer key insights into the molecular mechanisms driving these tumors and identify novel potential therapeutic targets, addressing the urgent need for more effective and less toxic treatments.

PMID:40348787 | DOI:10.1038/s41598-025-00763-3

BMC Plant Biol. 2025 May 10;25(1):620. doi: 10.1186/s12870-025-06622-7.

ABSTRACT

Trichomes in Prunus persica (L.) Batsch are crucial specialized structures that play a protective role against both biotic and abiotic stresses. The fruits with and without trichomes are respectively named as peach and nectarine. At the genetic level, the formation of trichome in peach is controlled by a single gene, PpMYB25, at the G locus. Peach (GG or Gg) is dominant to nectarine (gg), but such regulatory role was reported in a small-scale accession. In this study, we performed large-scale genotype and phenotype screening on 295 accessions. Almost all accessions supported the casual relationship between trichome formation and PpMYB25. However, a peach to nectarine mutant, named Maravilha Nectarine Mutant (MN), was discovered to possess a putative functional PpMYB25 gene sequence (Gg) but revealed nectarine phenotype. Comparative transcriptomic analyses revealed that PpMYB25 transcript was absent in MN. Correlation analyses also demonstrated that the PpMYB25-mediated regulatory network was abolished in MN. In summary, our results demonstrated an alternative mechanism beyond genetic regulation on trichome formation.

PMID:40348985 | DOI:10.1186/s12870-025-06622-7