J Comput Aided Mol Des. 2025 Jul 23;39(1):57. doi: 10.1007/s10822-025-00633-0.

ABSTRACT

Macrobrachium rosenbergii nodavirus is a major viral pathogen responsible for white tail disease in giant freshwater prawn aquaculture, leading to significant economic losses. In this study, a truncated DNA aptamer, TrAptm-1 was investigated for its binding properties against both monomeric and trimeric forms of the MrNV capsid proteins. Molecular dynamics simulations coupled with MM/PBSA binding free energy calculations revealed that TrAptm-1 exhibited a higher binding affinity to the trimeric capsid protein (-153.95 ± 6.74 kcal/mol) compared to the monomeric form (-120.77 ± 2.46 kcal/mol). TrAptm-1 binding induced significant conformational changes and structural rearrangements in the capsid protein, highlighted the antiviral potential of TrAptm-1 to interfere with the capsid protein self-assembly process. The observed structural changes demonstrated the importance of the oligomeric state in aptamer-capsid protein interactions, emphasizing that extended simulations up-to microseconds are required to capture the slow conformational rearrangements characteristic of large oligomeric protein complexes. These findings provide a molecular basis for the development of aptamer-based antiviral strategies, and the design of biosensor for early detection of MrNV in aquaculture settings.

PMID:40699462 | DOI:10.1007/s10822-025-00633-0

mBio. 2025 Jul 23:e0135525. doi: 10.1128/mbio.01355-25. Online ahead of print.

ABSTRACT

DNA regulatory elements that dictate how the bacterial pathobiont Haemophilus influenzae infects and adapts to the airways of immunocompromised patients suffering from chronic obstructive pulmonary disease (COPD) are poorly understood. This is in part due to the scarcity of research integrating genetic and epigenetic perspectives to shed light on the role of distinct bacterial adaptive strategies within the human airways. In this work, global fitness profiling of H. influenzae mutants by high-throughput transposon mutant sequencing within the mouse lung identified Dam methyltransferase as an in vivo requirement for respiratory infection. Equally, single-molecule real-time sequencing methylome analyses found undermethylation of GATC motifs within putative regulatory elements and revealed the first case of phenotypic variation controlled by variable Dam methylation in H. influenzae. Moreover, RNA sequencing differential gene expression disclosed a novel regulatory network where Dam methyltransferase positively regulates the expression of the ferric uptake regulator (Fur), which in turn represses the expression of the fumarate nitrate reductase (FNR) regulator and, subsequently, of a repertoire of genes that belong to the FNR regulon and encode bacterial anaerobic defenses against, among others, reactive nitrogen species produced within the diseased airways. Our results present a multifactorial regulatory network where the interplay between the Fur and FNR master transcriptional regulators is controlled epigenetically by Dam methylation. We put forward the notion that this network regulates H. influenzae survival in diseased airway niches with high nitrosative stress where damage reduces the amount of oxygen in the lungs, as encountered in COPD.

IMPORTANCE: Regulatory mechanisms governing the ability of Haemophilus influenzae to survive within the human lungs remain poorly elucidated. Here, by coordinated exploitation of multiomic approaches, and using reference and clinical strains, we present evidence that the Dam methyltransferase mediates epigenetic regulatory mechanisms facilitating bacterial phenotypic diversity and flexibility, besides reversibility, to contribute to H. influenzae survival within the lungs of individuals where disease reduces the amount of oxygen, as encountered in COPD. We reveal a novel bacterial network where DNA methylation regulates the expression of and interplay between the Fur and FNR master transcriptional regulators, which act in a coordinated manner, controlling the expression of H. influenzae genes involved in bacterial defenses against the nitrosative stress encountered in the diseased lungs, and further highlight the importance of oxygen restriction within this hostile niche.

PMID:40698946 | DOI:10.1128/mbio.01355-25

Protein Sci. 2025 Aug;34(8):e70231. doi: 10.1002/pro.70231.

ABSTRACT

The activities of [NiFe]-hydrogenase enzymes, which are critical to many microbes, require insertion of a Ni(II) ion into the bimetallic catalytic center. Delivery of Ni(II) to [NiFe]-hydrogenases depends, in part, on the metallochaperone HypB, which lies at the center of a Ni(II) transfer pathway that includes the metal storage protein SlyD and the metallochaperone HypA. SlyD is a source of Ni(II) ions for HypB, whereas Ni(II) from HypB is transferred to HypA. In this work, we examine how the intrinsically disordered N-terminal extension (NTE) of HypB modulates the action of the HypB GTPase domain (G-domain). The NTE contains a high-affinity Ni(II) binding site, while the G-domain contains a lower affinity Ni(II) binding site that is affected by binding of guanine nucleotides. The HypB G-domain is also affected by SlyD and provides Ni(II) to HypA. Our NMR data show that, although disordered, the HypB NTE possesses residual structure and makes transient interactions with the HypB G-domain and with SlyD. A set of common residues in the center of the NTE are affected by SlyD and G-domain binding, and also by binding of Ni(II) to the high-affinity site located at the N terminus of the protein. The NTE interacts with residues in or near the Ni(II)- and GDP-binding sites in the G-domain, which are also affected when SlyD binds the NTE. Thus, the data showcase a complex interaction network between HypB and SlyD, and provide molecular details regarding how the HypB NTE links the activities of the HypB G-domain and SlyD.

PMID:40698646 | DOI:10.1002/pro.70231

Quant Biol. 2025 Dec;13(4):e70007. doi: 10.1002/qub2.70007. Epub 2025 May 26.

ABSTRACT

Cellular aging is a multifaceted, complex process. Many genes and factors have been identified that regulate cellular aging. However, how these genes and factors interact with one another and how these interactions drive the aging processes in single cells remain largely unclear. Recently, computational systems biology has demonstrated its potential to empower aging research by providing quantitative descriptions and explanations of complex aging phenotypes, mechanistic insights into the emergent dynamic properties of regulatory networks, and testable predictions that can guide the design of new experiments and interventional strategies. In general, current complex systems approaches can be categorized into two types: (1) network maps that depict the topologies of large-scale molecular networks without detailed characterization of the dynamics of individual components and (2) dynamical models that describe the temporal behavior in a particular set of interacting factors. In this review, we discuss examples that showcase the application of these approaches to cellular aging, with a specific focus on the progress in quantifying and modeling the replicative aging of budding yeast Saccharomyces cerevisiae. We further propose potential strategies for integrating network maps and dynamical models toward a more comprehensive, mechanistic, and predictive understanding of cellular aging. Finally, we outline directions and questions in aging research where systems-level approaches may be especially powerful.

PMID:40697249 | PMC:PMC12277577 | DOI:10.1002/qub2.70007

Biofilm. 2025 Jul 2;10:100301. doi: 10.1016/j.bioflm.2025.100301. eCollection 2025 Dec.

ABSTRACT

Pseudomonas aeruginosa biofilms cause severe infections in the airways of patients suffering from cystic fibrosis (CF) that are difficult to eradicate, even with intensive antibiotic therapy. The main goal of this study was to define the dual transcriptional response associated with the formation of P. aeruginosa biofilms in a polarized lung epithelium monolayer. We analyzed the dual response of healthy and CF epithelium after infection with P. aeruginosa isolates from acute and chronic infections. Our results show that strains of P. aeruginosa isolated from chronic infections specifically increase the expression of secretion systems of type I, III and VI to hijack the host response. Conversely, strains associated with acute illness use ABC transporters to counteract the antimicrobial response. In return, a distinctive expression pattern in the CF epithelium, including a high degree of cytokine secretion and keratinization, is largely observed in acute infections. Our results show that both host and pathogen genomic backgrounds contribute to the outcome of infection and specific transcriptional signatures could be used in the diagnosis, particularly in CF patients.

PMID:40697188 | PMC:PMC12281032 | DOI:10.1016/j.bioflm.2025.100301

Plant Cell. 2025 Jul 1;37(7):koaf143. doi: 10.1093/plcell/koaf143.

ABSTRACT

Microscopy is a fundamental approach for plant cell and developmental biology as well as an essential tool for mechanistic studies in plant research. However, setting up a new microscopy-based experiment can be challenging, especially for beginner users, when implementing new imaging workflows or when working in an imaging facility where staff may not have extensive experience with plant samples. The basic principles of optics, chemistry, imaging, and data handling are shared among all cell types. However, unique challenges are faced when imaging plant specimens due to their waxy cuticles, strong/broad spectrum autofluorescence, recalcitrant cell walls, and air spaces that impede fixation or live imaging, impacting sample preparation and image quality. As expert plant microscopists, we share our collective experience on best practices to improve the quality of published microscopy results and promote transparency, reproducibility, and data reuse for meta-analyses. We offer plant-specific advice and examples for microscope users at all stages of fluorescence microscopy workflows, from experimental design through sample preparation, image acquisition, processing, and analyses, to image display and methods reporting in manuscripts. We also present standards for methods reporting that will be valuable to all users and offer tools to improve reproducibility and data sharing.

PMID:40697154 | DOI:10.1093/plcell/koaf143

J Chem Inf Model. 2025 Jul 23. doi: 10.1021/acs.jcim.5c00431. Online ahead of print.

ABSTRACT

This study presents a computationally efficient approach to generate plausible protein conformers for ensemble docking to enable evaluations of interactions between ligand and protein for ranking the docked ligands according to their binding affinities. Two binding regions of triose phosphate isomerase (TIM), its catalytic site with DHAP (G. gallus TIM), and its dimer interface with 3PG (P. falciparumTIM) involving flexible loops were investigated as case studies. The binding sites of the apo and holo forms were modeled at the atomistic scale (high resolution) while the remaining structure was coarse-grained (low resolution) leading to a mixed-resolution description of the protein. The slowest three normal modes related to the functional dynamics of TIM were obtained using the Anisotropic Network Model and employed to derive 36 conformers of the truncated high-resolution regions by assessing six deformation parameters in both directions of the harmonic motions. Through energy minimization and docking calculations in Glide, optimal extents of deformation were identified. The docked truncated structures were then subjected to independent molecular dynamics (MD) simulations to confirm the interactions of the ligands in the binding sites. To prevent the disintegration of the truncated structure, different buffer zones and harmonic restraints were assessed to finally decide on four distinct zones with restraints of 0, 25, 35, and 50 kcal/mol·Å2. Each conformer underwent 900 ns-long simulations across three replicates reaching a total simulation time of 15.2 μs. Binding free energy calculations were conducted using the MM-GBSA approach using the first 50, first 100, first 200, and 300 ns intervals, which pointed out that 100 ns-long simulations were sufficient to estimate the binding affinities for TIM. Results consistently indicated comparable binding energies between the intact and truncated TIM structures underscoring the approach's reliability, where the truncated conformers also offered varying binding site geometries yielding favorable interactions. Comparative docking at the dimer interface of G. gallus and P. falciparum TIM further highlighted species-specific binding dynamics, affirming the methodology's applicability for diverse biological questions and establishing a computationally efficient approach to estimate binding free energy values even for supramolecular assemblages.

PMID:40696994 | DOI:10.1021/acs.jcim.5c00431

FEBS Lett. 2025 Jul 22. doi: 10.1002/1873-3468.70122. Online ahead of print.

ABSTRACT

The evolutionary expansion of 3' untranslated regions (3'UTRs), along with the incorporation of transposable elements and alternative polyadenylation (APA) sites, has introduced additional layers of gene expression control in eukaryotes. Consequently, 3'UTRs regulate the stability, translation, and localization of mRNAs by interacting with RNA-binding proteins and non-coding RNAs, thereby contributing to cell-type-specific and context-dependent gene expression. Mounting evidence highlights the importance of non-coding regions, particularly 3'UTRs, in normal physiology and disease states, including cancer. Genomic alterations and driver mutations in coding regions play a well-established role in cancer biology. Advances in long-read sequencing and 3'UTR-focused genome-/transcriptome-wide association studies (GWAS/TWAS) improve our understanding of transcriptome complexity and how mRNA isoforms with different 3'-ends may impact protein functions. This Review explores the regulatory roles of 3'UTRs, sources of 3'UTR isoform diversity, and implications in cancer, emphasizing the need for further research into their diagnostic and therapeutic potential. Impact statement This review highlights how alternative polyadenylation generates diverse mRNA 3'-end isoforms in cancer. Isoforms with distinct 3'UTRs are differentially regulated by microRNAs and RNA-binding proteins, while intronically polyadenylated isoforms can lead to C-terminally truncated proteins with altered functions.

PMID:40696497 | DOI:10.1002/1873-3468.70122

Genome Biol. 2025 Jul 22;26(1):217. doi: 10.1186/s13059-025-03667-7.

ABSTRACT

BACKGROUND: Understanding the role of cancer hotspot mutations is essential for unraveling mechanisms of tumorigenesis and identifying therapeutic vulnerabilities. Correcting cancer mutations with base editing is a novel, yet promising approach for investigating the biology of driver mutations.

RESULTS: Here, we present a versatile platform to investigate the functional impact of cancer hotspot mutations through adenine base editing in combination with transcriptomic profiling. Using this approach, we correct TP53 hotspot mutations in cancer cell lines derived from diverse tissues, followed by mRNA sequencing to evaluate transcriptional changes. Remarkably, correcting these mutations not only reveals the dependency on mutant allele expression but also restores highly conserved tumor-suppressive transcriptional programs, irrespective of tissue origin or co-occurring mutations, highlighting a shared p53-dependent regulatory network. Our findings demonstrate the utility of this base editing platform to systematically interrogate the functional consequences of cancer-associated mutations and their downstream effects on gene expression.

CONCLUSIONS: This work establishes a robust framework for studying the transcriptional dynamics of cancer hotspot mutations and sheds light on the conserved biological processes reinstated by p53 correction, offering potential avenues for future targeted therapies.

PMID:40696461 | DOI:10.1186/s13059-025-03667-7

Genome Biol. 2025 Jul 22;26(1):216. doi: 10.1186/s13059-025-03684-6.

ABSTRACT

Single-cell RNA-seq data from clinical samples often suffer from batch effects, but data sharing is limited due to genomic privacy concerns. We present FedscGen, a privacy-preserving communication-efficient federated method built upon the scGen model, enhanced with secure multiparty computation. FedscGen supports federated training and batch effect correction workflows, including the integration of new studies. We benchmark FedscGen across diverse datasets, showing competitive performance-matching scGen on key metrics like NMI, GC, ILF1, ASW_C, kBET, and EBM on the Human Pancreas dataset. Published as a FeatureCloud app, FedscGen enables secure, real-world collaboration for scRNA-seq batch effect correction.

PMID:40696440 | DOI:10.1186/s13059-025-03684-6

Nat Biotechnol. 2025 Jul 22. doi: 10.1038/s41587-025-02734-5. Online ahead of print.

ABSTRACT

Measuring splicing and chromatin accessibility simultaneously in frozen tissues remains challenging. Here we combined single-cell isoform RNA sequencing and assay for transposase accessible chromatin (ScISOr-ATAC) to interrogate the correlation between these modalities in single cells in human and rhesus macaque frozen cortical tissue samples. Applying a previous definition of four 'cell states' in which the transcriptome and chromatin accessibility are coupled or decoupled for each gene, we demonstrate that splicing patterns in one cell state can differ from those of another state within the same cell type. We also use ScISOr-ATAC to measure the correlation of chromatin and splicing across brain cell types, cortical regions and species (macaque and human) and in Alzheimer's disease. In macaques, some excitatory neuron subtypes show brain-region-specific splicing and chromatin accessibility. In human and macaque prefrontal cortex, strong evolutionary divergence in one molecular modality does not necessarily imply strong divergence in another modality. Finally, in Alzheimer's disease, oligodendrocytes show high dysregulation in both chromatin and splicing.

PMID:40696189 | DOI:10.1038/s41587-025-02734-5

Nat Cancer. 2025 Jul 22. doi: 10.1038/s43018-025-01009-x. Online ahead of print.

ABSTRACT

Chimeric antigen receptor (CAR)-engineered lymphocytes treat B cell malignancies; however, limited persistence can restrain the full therapeutic potential of this approach. FAS ligand (FAS-L)/FAS interactions govern lymphocyte homeostasis. Knowledge of which cells express FAS-L in patients with cancer and whether these sources compromise CAR persistence remains incomplete. Here, we constructed a single-cell atlas of diverse cancers to identify cellular subsets expressing FASLG, the gene encoding FAS-L. We discovered that FASLG expression is limited primarily to endogenous T cells, natural killer (NK) cells and CAR-T cells, while tumor and stromal cell expression is minimal. To establish whether CAR-T and CAR-NK cell survival is FAS-L regulated, we performed competitive fitness assays using FAS-dominant negative receptor (ΔFAS)-modified lymphocytes. Following transfer, ΔFAS-expressing CAR-T/CAR-NK cells became enriched, a phenomenon that mechanistically was reverted through FASLG knockout. By contrast, FASLG was dispensable for CAR-mediated tumor killing. In multiple models in female mice, ΔFAS coexpression enhanced antitumor efficacy. Together, these findings reveal that CAR-engineered lymphocyte persistence is governed by a FAS-L/FAS autoregulatory circuit.

PMID:40696154 | DOI:10.1038/s43018-025-01009-x

Cell Death Differ. 2025 Jul 23. doi: 10.1038/s41418-025-01549-w. Online ahead of print.

ABSTRACT

Rezatapopt is an investigational small molecule p53 reactivator that binds specifically to the Y220C-mutant p53 protein without interacting with wild-type or other mutant p53 proteins. Upon binding, rezatapopt stabilizes the Y220C-mutant p53 protein in the wild-type conformation, reactivating p53 functions. The Phase 1 PYNNACLE trial assessed rezatapopt in solid tumors. One study participant with triple-negative breast cancer experiencing severe inflammation of the skin overlying the breast and left arm edema saw inflammation improve within 1 week of receiving rezatapopt and completely resolve shortly after. After 6 weeks of treatment, tumor volume had reduced 41%. The patient remains on study, with continued resolution of the skin inflammation and reduced tumor burden for greater than 24 months. There are several wild type Tp53 regulated pathways that could play a role in reversing the inflammatory response and tumor growth observed in this patient case. This perspective explores the signal transduction pathways involved in this cancer mediated inflammation and the extensive reduction of detectable tumor tissue.

PMID:40696138 | DOI:10.1038/s41418-025-01549-w

NPJ Syst Biol Appl. 2025 Jul 22;11(1):81. doi: 10.1038/s41540-025-00559-1.

ABSTRACT

Understanding the complex interplay between host and pathogen during infection is critical for developing diagnostics and improving therapeutic interventions. Among the diverse arsenal employed by the host, antimicrobial peptides (AMP) play a key role in the defense against pathogens. We propose an immune evasion mechanism termed "Complex-mediated evasion" (CME), that allows pathogens to protect themselves against AMP and investigate it through mathematical modeling and computer simulations. To achieve CME, we hypothesize that the pathogen secretes defense molecules that bind AMP. When bound within the complex, AMP are unable to harm the pathogen. Due to molecular gradients, complexes may diffuse away from the pathogen, enhancing the protective effect of the mechanism by decreasing the concentration of AMP in the vicinity of the pathogen. We establish a mathematical model to (i) explore the sensitivity of the mechanism to various parameters and (ii) simulate the immune evasion of the human-pathogenic fungus Candida albicans.

PMID:40695781 | DOI:10.1038/s41540-025-00559-1

Biotechnol Adv. 2025 Jul 20:108651. doi: 10.1016/j.biotechadv.2025.108651. Online ahead of print.

ABSTRACT

Flavoprotein monooxygenases (FPMOs) form a broad superfamily of enzymes that catalyze the oxyfunctionalization of a wide range of substrates, playing a crucial role in biocatalysis and sustainable chemistry. Among them, Class A enzymes are the most extensively studied, with well-established knowledge of their reaction mechanisms, stereoselectivity, and substrate scope. However, the full potential of this enzyme class remains largely untapped, as many valuable catalysts have yet to be identified and characterized. In this review, we employ a structural biology approach to provide an up-to-date overview of current knowledge on class A FPMOs. We first discuss the overall structure and catalytic mechanism. Then we present a systematic overview of all the known enzymes categorizing them biochemically as either prototypical or atypical and illustrating how similar protein scaffolds can give rise to markedly different reactions. Subsequently we discuss the co-factor preference and the protein engineering approaches. Finally, we explore uncharted areas of this field offering a strategy for discovering new catalysts.

PMID:40695392 | DOI:10.1016/j.biotechadv.2025.108651

Fitoterapia. 2025 Jul 20:106740. doi: 10.1016/j.fitote.2025.106740. Online ahead of print.

ABSTRACT

This manuscript investigates the phytochemical composition and biological potential of Chrozophora tinctoria extracts obtained with solvents of different polarities (ethyl acetate, ethanol, 70 % ethanol, and water). Comprehensive in vitro analyses revealed that ethanol and ethyl acetate extracts had the highest levels of phenolic and flavonoid compounds, which corresponded with strong antioxidant activity and significant inhibitory effects on key enzymes such as acetylcholinesterase, butyrylcholinesterase, α-amylase, α-glucosidase, and tyrosinase. Cytotoxicity tests on several human cell lines showed that the plant species tested did not exhibit cytotoxic activity. LC-MS-qTOF analysis identified bioactive components, with apigenin emerging as one of the most interesting compounds. An integrated in silico approach involving network pharmacology, molecular docking, and molecular dynamics simulations revealed strong and stable interactions between apigenin and therapeutic targets involved in neurodegenerative and metabolic processes. These findings could serve as an outline for future studies on the medicinal plant's potential.

PMID:40695382 | DOI:10.1016/j.fitote.2025.106740

Dev Cell. 2025 Jul 14:S1534-5807(25)00412-5. doi: 10.1016/j.devcel.2025.06.034. Online ahead of print.

ABSTRACT

Esophageal adenocarcinoma arises from Barrett's esophagus, a metaplastic condition. Multi-omics profiling, integrating single-cell transcriptomics, extracellular matrix proteomics, tissue mechanics and spatial proteomics of the paths of progression from squamous epithelium through metaplasia, dysplasia to adenocarcinoma, in 107 samples from 26 patients in two independent cohorts, defined shared and patient-specific progression characteristics. Metaplastic replacement of epithelial cell composition and architecture was paralleled by changes in stromal cells, extracellular matrix (ECM) and tissue stiffness. This change in pre-cancerous metaplasia was already accompanied by appearance of fibroblasts with the molecular characteristics of carcinoma-associated fibroblasts. These fibroblasts produced the immunosuppressive protein POSTN, whose expression shifted from vascular to stromal cells, consistent with the emergence of an immunosuppressive microenvironment evident in cell neighborhoods enriched for immunoregulatory NK and Treg cells. Thus, Barrett's esophagus progresses as a coordinated multi-component system, supporting treatment paradigms that go beyond targeting cancerous cells to incorporate stromal reprogramming.

PMID:40695287 | DOI:10.1016/j.devcel.2025.06.034

JCI Insight. 2025 Jul 22:e184280. doi: 10.1172/jci.insight.184280. Online ahead of print.

ABSTRACT

RNA splicing factor SF3B1 is one of the most recurrently mutated genes in chronic lymphocytic leukemia (CLL) and frequently co-occurs with chromosome 13q deletion (del(13q)). This combination is associated with poor prognosis in CLL, suggesting these lesions increase CLL aggressiveness. While del(13q) in murine B cells (Mdr mice), but not expression of Sf3b1-K700E, drives the initiation of CLL, we hypothesize that SF3B1 mutation accelerates CLL progression. In this study, we crossed mice with a B-cell-specific Sf3b1-K700E allele with Mdr mice to determine the impact of Sf3b1 mutation on CLL progression. We found that the co-occurrence of these two lesions in murine B cells caused acceleration of CLL. We showed that Sf3b1-K700E impacted alternative RNA splicing of Nfatc1 and activated mTOR signaling and the MYC pathway, contributing to CLL acceleration. Moreover, concurrent inhibition of RNA splicing and mTOR pathways led to cell death in vitro and in vivo in murine CLL cells with SF3B1 mutation and del(13q). Our results thus suggest that SF3B1 mutation contributes to the aggressiveness of CLL by activating the mTOR pathway through alternative splicing of Nfatc1, providing a rationale for targeting mTOR and RNA splicing in the subset of CLL patients with both SF3B1 mutations and del(13q).

PMID:40694421 | DOI:10.1172/jci.insight.184280

Elife. 2025 Jul 22;13:RP96421. doi: 10.7554/eLife.96421.

ABSTRACT

Cell polarization is a critical process that separates molecular species into two distinct regions in prokaryotic and eukaryotic cells, guiding biological processes such as cell division and cell differentiation. Although several underlying antagonistic reaction-diffusion networks capable of setting up cell polarization have been identified experimentally and theoretically, our understanding of how to manipulate pattern stability and asymmetry remains incomplete, especially when only a subset of network components is known. Here, we present numerical results to show that the polarized pattern of an antagonistic 2-node network collapses into a homogeneous state when subjected to single-sided self-regulation, single-sided additional regulation, or unequal system parameters. However, polarity restoration can be achieved by combining two modifications with opposing effects. Additionally, spatially inhomogeneous parameters favoring respective domains stabilize their interface at designated locations. To connect our findings to cell polarity studies of the nematode Caenorhabditis elegans zygote, we reconstituted a 5-node network where a 4-node circuit with full mutual inhibitions between anterior and posterior is modified by a mutual activation in the anterior and an additional mutual inhibition between the anterior and posterior. Once again, a generic set of kinetic parameters moves the interface towards either the anterior or posterior end, yet a polarized pattern can be stabilized through tuning of one or more parameters coupled to intracellular or extracellular spatial cues. A user-friendly software, PolarSim, is constructed to facilitate the exploration of networks with alternative node numbers, parameter values, and regulatory pathways.

PMID:40693535 | DOI:10.7554/eLife.96421

Psychiatry Clin Psychopharmacol. 2025 Apr 16;35(2):102-110. doi: 10.5152/pcp.2025.24896. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: The present study aimed to find the electroencephalography (EEG) characteristics of adult attention-deficit/hyperactivity disorder (ADHD) and to examine if these EEG indices are associated with insomnia in adult ADHD.

METHODS: Twenty-six participants were included in the adult ADHD group, and 26 sex-, age-, and education-matched participants formed the control group. Between-group differences in the resting-state EEG indices and the score of insomnia scale were assessed. Correlational analysis between these EEG indices and the score of insomnia scale was conducted.

RESULTS: The adult ADHD group had more insomnia problems and showed increased power over 4 frequency bands at electrodes frontal area, Cz, and Pz, except for alpha band at electrode frontal area. Furthermore, some EEG indices, especially over fast frequency bands, are associated with the score of insomnia scale.

CONCLUSION: The findings of this study reveal that adult ADHD shows a distinct EEG pattern during the resting state. The correlation between the EEG indices over fast frequency bands in adult ADHD and the score of the insomnia scale may explain the high prevalence of insomnia in adult ADHD.

PMID:40693107 | PMC:PMC12277769 | DOI:10.5152/pcp.2025.24896