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At least 19 recordsLinked to original sources

PubMed2026

Longitudinal functional network connectivity changes across the clinical stages of C9orf72 hexanucleotide repeat expansion carriers.

INTRODUCTION: Intrinsic functional connectivity network abnormalities in C9orf72 hexanucleotide repeat expansion carriers emerge during the asymptomatic phase, yet longitudinal studies remain limited. We examined cross-sectional abnormalities and longitudinal connectivity changes across clinical stages. METHODS: We analyzed task-free functional magnetic resonance imaging (fMRI) and structural MRI data in 36 asymptomatic (aSxC9), 17 prodromal (proC9), and 29 symptomatic (SxC9) carriers, and 107 healthy controls (HCs). Functional networks previously found altered in C9orf72, including salience, sensorimotor, default mode, and medial pulvinar thalamic networks, were examined. Associations between longitudinal connectivity and gray matter decline with baseline neurofilament light chain (NfL) concentrations and symptom severity were assessed. RESULTS: aSxC9 and SxC9 showed longitudinal connectivity changes within specific networks. In aSxC9, connectivity changes correlated with baseline NfL. In proC9 and SxC9, changes in connectivity and gray matter were associated with baseline NfL and symptom severity. DISCUSSION: C9orf72 expansion carriers demonstrate stage-specific network connectivity changes.

Humans↗

PubMed2026

Dynamic Fusion of Genomics and Functional Network Connectivity in UK Biobank Reveals Schizophrenia-Related SNP Manifolds.

Many mental disorders show strong genetic influence. In parallel, dynamic functional network connectivity (dFNC) has shown high sensitivity to brain changes related to mental disorders. However, previous studies linking dFNC to genetics largely follow a paradigm to identify associations between one set of genetic factors and multiple sets of connectivity features from different dFNC states, ignoring the potential variability in genetic correlates across states. We propose a novel joint ICA (jICA)-based "dynamic fusion" framework to identify dynamically tuned genetic manifolds. A sliding window approach was utilized to estimate four dFNC states and compute subject-level state-average dFNC (sa-dFNC) features. The sa-dFNC features of each state were combined with schizophrenia risk single nucleotide polymorphisms (SNPs) within a jICA fusion framework, resulting in four parallel fusions in 32,861 individuals of the UK Biobank cohort. The extracted four sets of joint SNP-dFNC components were further validated for clinical relevance in a combined schizophrenia cohort of 820 individuals (348 patients). The similarity of SNP-dFNC components across four parallel fusions was evaluated as a measure of state variability. We observed a mixture of "state-invariant" and "state-variant" components for SNP and dFNC modalities. Particularly, the schizophrenia-related state-variant SNP components, or manifolds, complemented each other by capturing different SNPs involved in the same biological functions, revealing a partition of genomic risk particularly elicited by the dynamics of brain function. By augmenting the SNP factors to state-variant manifolds, this dynamic fusion framework promises additional insights into the underlying genetic risk of disease-related alterations in dynamic brain function.

Humans↗

PubMed2025

NOODAI: a webserver for network-oriented multi-omics data analysis and integration pipeline.

SUMMARY: Omics profiling has proven of great use for unbiased and comprehensive identification of key features that define biological phenotypes and underlie medical conditions. While each omics profile assists characterization of specific molecular components relevant for the studied phenotype, their joint evaluation can offer deeper insights into the overall mechanistic functioning of biological systems. Here, we introduce an approach where, starting from representative traits (e.g. differentially expressed elements) obtained for each omics profile, we construct and analyze joint interaction networks. The resulting networks rely on the existing knowledge of confident interactions among biological entities. We use these maps to identify and describe central elements, which connect multiple entities characteristic of the studied phenotypes and we leverage MONET network decomposition tool in order to highlight functionally connected network modules. In order to enable broad usage of this approach, we developed the NOODAI software platform, which enables integrative omics analysis through a user-friendly interface. The analysis outcomes are presented both as raw output tables as well as informative summary plots and written reports. Since the MONET tool enables the use of algorithms with strong performance in identifying disease-relevant modules, NOODAI software platform can be of a high value for analyzing clinical multi-omics datasets. AVAILABILITY AND IMPLEMENTATION: NOODAI is freely accessible at https://omics-oracle.com. Source code is available under GPL3 at: https://github.com/TotuTiberiu/NOODAI with the DOI: 10.5281/zenodo.17203984.

Software↗

PubMed2025

Brain dynamics reflecting an intra-network brain state is associated with increased posttraumatic stress symptoms in the early aftermath of trauma.

Post-traumatic stress (PTS) encompasses a range of psychological responses following trauma, which may lead to more severe outcomes such as post-traumatic stress disorder (PTSD). Identifying early neuroimaging biomarkers that link brain function to PTS outcomes is critical for understanding PTSD risk. This longitudinal study examines the association between brain dynamic functional network connectivity (dFNC) and current/future PTS symptom severity, and the impact of sex on this relationship. By analyzing 275 participants' dFNC data obtained ~2 weeks after trauma exposure, we noted that brain dynamics of an inter-network brain state link negatively with current (r=-0.197, p corrected = 0.0079) and future (r=-0.176, p corrected = 0.0176) PTS symptom severity. Also, dynamics of an intra-network brain state correlated with future symptom intensity (r = 0.205, p corrected = 0.0079). We additionally observed that the association between the network dynamics of the inter-network and intra-network brain state with symptom severity is more pronounced in female group. Our findings highlight a potential link between brain network dynamics in the aftermath of trauma with current and future PTSD outcomes, with a stronger effect in female group, underscoring the importance of sex differences.

Journal Article↗

PubMed2025

Glaucoma and brain functional networks: a bidirectional Mendelian randomisation study.

OBJECTIVE: Glaucoma is a complex neurodegenerative ocular disorder accompanied by brain functional abnormalities that extend beyond the visual system. However, the causal association between the two remains unclear at present. This study aimed to investigate the potential causal relationships between glaucoma and brain functional networks in order to provide novel insights into the neuropathic mechanism of glaucoma. METHODS AND ANALYSIS: Based on the genome-wide association studies data of glaucoma and resting-state functional MRI (Rs-fMRI), a bidirectional Mendelian randomisation (MR) analysis was conducted between glaucoma and brain functional networks. Inverse variance weighting was applied as the primary method to estimate causality with false discovery rate correction. Additional sensitivity analyses were conducted to evaluate the robustness of the results. RESULTS: Forward MR analysis suggested that glaucoma was causally associated with two brain networks between the subcortical cerebellum and the attention or visual network (p=0.022), as well as the default mode and central executive network (p=0.008), but without significance after false discovery rate correction (q>0.1). Reverse MR analysis revealed 19 Rs-fMRI traits related to glaucoma risk, including the salience or central executive network in the frontal region (p=0.0005, q=0.08) and the motor network (p=0.0009, q=0.08) with significant causality. CONCLUSIONS: This MR study revealed potentially causal relationships between glaucoma and brain functional networks. Especially, the functional connectivity of the motor network between the postcentral or precentral areas may potentially lead to increased risk of glaucoma.

Humans↗

PubMed2026

Dual Transcranial Direct Current Stimulation Modulates Hierarchical Functional Network Organization in Post-Stroke Cognitive Impairment: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the clinical efficacy of dual transcranial direct current stimulation (tDCS) in patients with post-stroke cognitive impairment (PSCI) and to explore the effects on the hierarchical organization of functional brain networks, ranging from regional synchronization to inter-regional connectivity and global network topology. METHODS: In this randomized, double-blind, sham-controlled trial, 74 PSCI patients received conventional therapy alongside either active dual-tDCS (n = 38) or sham stimulation (n = 36). Active tDCS targeted the dorsolateral prefrontal cortex (DLPFC) via anodal-left/cathodal-right nodes (2.0 mA, 20 min/day, 20 sessions). The primary outcome was the Montreal Cognitive Assessment (MoCA). Secondary outcomes included the Mini-Mental Status Examination (MMSE), Stroop Test (ST), Trail Making Test (TMT), Wechsler Memory Scale (WMS), and Barthel Index (BI). A subgroup of 36 participants (18 per group) underwent resting-state functional magnetic resonance imaging (rs-fMRI) to analyze regional homogeneity (ReHo), functional connectivity (FC), and network topology. Partial correlations assessed the association between neuroimaging alterations and clinical improvements. RESULTS: The tDCS group showed significantly greater improvements in MoCA scores (tDCS: 5.74 ± 2.76 vs. sham: 2.69 ± 2.69; t = 4.799, p < 0.001) as well as in attention and memory domains compared to the sham group. The rs-fMRI changes included increased ReHo in the right middle temporal gyrus (MTG) and the left inferior frontal gyrus (IFG), and reduced FC between the right MTG-left superior frontal gyrus and left IFG-cerebellum (p < 0.05, FWE-corrected). Additionally, small-worldness and global efficiency increased (p < 0.05) with these alterations correlating with clinical recovery. Adverse events were rare and self-limiting. CONCLUSION: Dual-tDCS over bilateral DLPFC safely improves cognitive recovery in PSCI. These clinical gains are associated with rs-fMRI alterations, specifically in regional synchronization, inter-regional connectivity, and global topology, which suggest a potential biomarker for monitoring tDCS efficacy, offering a rationale for precision neuromodulation in stroke rehabilitation.

Humans↗

PubMed2026

Functional mapping of the Trypanosoma cruzi serinome by fluorophosphonate activity-based protein profiling.

Serine hydrolases (SHs) constitute one of the largest enzyme superfamilies in eukaryotes, yet their roles in Trypanosoma cruzi, the causative agent of Chagas disease, remain largely uncharacterized. Here, we report an activity-based chemoproteomic map of the T. cruzi epimastigote serinome by combining genome-informed in silico curation with whole-cell activity-based protein profiling (ABPP) using a panel of cell-permeable fluorophosphonate (FP)-alkyne probes. Whole-cell labelling followed by label-free quantitative proteomics (LFQ-MS) identified 37 enriched SH-like proteins, including 35 with conserved or partially conserved catalytic triad/dyad features, spanning lipases, peptidases, esterases, and previously uncharacterized hydrolases. The 35 SHs represent approximately 63% of the 56 predicted SHs retained after catalytic-site curation. Domain architecture analysis revealed broad structural diversity, while orthologue-based localization data suggested association with multiple subcellular compartments, including glycosomal, mitochondrial, and endosomal localizations. Gene Ontology enrichment highlighted lipid metabolic and catabolic processes as dominant functional themes, and protein-protein interaction network analysis supported functional connectivity among the captured enzymes. Several identified SHs, including oligopeptidase B, prolyl oligopeptidase Tc80, serine carboxypeptidase CPB1, and phospholipase A1 (PLA1) have previously been characterized in trypanosomatids, with roles linked to parasite virulence or host-pathogen interactions. Together, these findings establish a fluorophosphonate-based chemoproteomic resource for the kinetoplastid community and prioritize probe-accessible active T. cruzi SHs for future functional validation and antiparasitic inhibitor discovery.

Activity-based protein profiling↗

PubMed2026

Schizophrenia and bipolar disorder: a comparative analysis of genetic and brain network connectivity.

BACKGROUND: Schizophrenia (SCZ) and bipolar disorder (BD) are severe psychiatric conditions with overlapping clinical presentations, genetic risk factors, and brain network dysfunction. Whether alterations in large-scale intrinsic brain networks reflect shared or disorder-specific genetic influences remains poorly understood. Clarifying this distinction is essential for refining etiological models and improving diagnostic precision. METHODS: Genome-wide inferred statistics (GWIS) were applied to decompose the genetic architecture of SCZ and BD into shared and unique components. Using resting-state network (RSN) data from the UK Biobank, functional connectivity (FC) and structural connectivity (SC) were extracted as neuroimaging phenotypes. Causal inference approaches were subsequently employed to infer potential directional relationships between brain network connectivity and each disorder. RESULTS: Analyses revealed both common and distinct patterns of brain network connectivity associated with SCZ and BD. Notably, SC within the default mode network (DMN) exhibited opposing effects across the two disorders, suggesting divergent structural underpinnings despite clinical overlap. Additionally, SC within the limbic network (LN) and frontotemporal control network demonstrated potential causal relationships with both conditions, implicating these circuits astransdiagnostic neural substrates. CONCLUSION: These findings illuminate the shared and disorder-specific genetic and neural architecture underlying SCZ and BD. Integrating genome-wide genetic methods with large-scale neuroimaging data offers a powerful framework for disentangling psychiatric comorbidity and may inform more targeted diagnostic criteria and individualized treatment strategies.

Humans↗

PubMed2025

Interrogating functional connectivity of in vitro neural glia tissue model modulated through integrative control of matrix stiffness and a neurotrophic factor.

Brain function emerges from intricate cellular communication within neural networks. Both In silico neuronal models and primary neuron cells have revealed that the branching architecture of individual neurons determines the bioelectrical signal propagation pattern and dynamics. However, whether stem cell-differentiated neurons can build functional connectivity regulated by neuronal morphology has yet to be determined. Here, we hypothesized that neurite length, branching, or both factors would regulate the functional connectivity of the stem cell-differentiated neural network. We examined this hypothesis by differentiating mouse cortical neural stem cells (NSCs) on Matrigel substrates with varying storage moduli, both with and without basic fibroblast growth factor (bFGF). Interestingly, with bFGF, Matrigel with a storage modulus (G') of 100 Pa drives NSCs to differentiate into neurons with more dendritic branches, while the gel with G' of 50 Pa led to the development of longer neurites with fewer branches. Notably, branch-rich neural networks exhibited an increased frequency of calcium transients. Using a MATLAB-based analysis pipeline incorporating graph theory, we constructed spatial and temporal calcium activity maps, revealing that branching complexity, more than neurite length, correlates with the density and strength of functional neural circuits. Overall, this study demonstrates that the dendritic branching of neurons, modulated with matrix stiffness and neurotrophic factors, is a key element in enhancing the electrophysiological functionality of the stem cell-differentiated neural network. This finding will have a significant impact on efforts to reconstruct functional neural tissue models, advancing both regenerative therapies and unexplored applications, including biological computing.

Animals↗

PubMed2025

Depth-dependent multi-kingdom microbial interactions and biogeochemical cycling genes in eutrophic shallow lake sediments.

Microorganisms are pivotal to lake ecosystem biogeochemical cycles, yet existing research often focuses on single microbial kingdoms or surface sediments, neglecting multi-kingdom interactions and depth-resolved dynamics. To address these gaps, we used metagenomic sequencing to characterize microbial communities and their functional associations across overlying water and 0-45 cm sediments in four shallow lakes of the middle Yangtze River basin, China. Despite increasing bacterial and fungal diversity with depth, the 0-9 cm surface sediments exhibited the strongest multi-kingdom network connectivity and the greatest microbial stability. Functional genes exhibited clear depth-dependent patterns: nitrogen cycling genes, including those involved in dissimilatory nitrate reduction to ammonium, were most enriched in the upper 0-9 cm of sediment; methane cycling genes were positively correlated with depth; phosphorus cycling genes and some sulfur cycling genes, such as assimilatory sulphate reduction, declined with depth. Sediment microbial assembly was dominated by deterministic processes, in which the vertical distribution of functional genes was primarily dictated by heavy metals and conventional environmental indicators. These findings highlight depth-specific multi-kingdom microbial interactions and their associations with biogeochemical cycling, advancing lacustrine microbial ecology understanding and providing references for lake conservation under environmental change.

Lakes↗

PubMed2026

Comparison of the clinical efficacy, safety and EEG functional connectivity changes between 18-Hz rTMS and iTBS of accelerated dTMS treatment for major depressive disorder: a randomized controlled trial.

Although the antidepressant efficacy of 18-Hz deep transcranial magnetic stimulation (dTMS) has been validated, its prolonged treatment duration has considerable limitations for treatment capacity and patient adherence. Therefore, novel short-course protocols such as accelerated dTMS and intermittent theta burst stimulation (iTBS) present promising alternative options. Here we addressed the question of whether iTBS of accelerated dTMS achieves comparable therapeutic and electrophysiological effects to accelerated dTMS with the conventional 18-Hz rTMS protocol in patients with major depressive disorder (MDD). In a randomized controlled trial (n = 73), participants received either 18-Hz rTMS of accelerated dTMS (rTMS-dTMS group), iTBS of accelerated dTMS (iTBS-dTMS group), or pharmacotherapy alone (drug group). Both dTMS protocols were administered twice daily for 10 days targeting the left lateral prefrontal cortex including the dorsolateral region. Results showed that Hamilton Depression Rating Scale (HAMD) score of the iTBS-dTMS group decreased significantly from 22.5 ± 3.7 before treatment to 8.2 ± 4.1 after treatment (t = 15.900, p < 0.001). HAMD score of the rTMS-dTMS group decreased significantly from 21.3 ± 2.9 before treatment to 8.0 ± 3.8 after treatment (t = 17.232, p < 0.001). The drug group also exhibited significantly improved patients' mood symptoms, and the HAMD score decreased from 24.7 ± 6.8 to 14.0 ± 5.0 (t = 6.363, p < 0.001). The treatment response rate was 85.7% in the iTBS-dTMS group and 76.9% in the rTMS-dTMS group, which was much higher than that of the drug group (42.1%). The remission rate was 50.0% in the iTBS-dTMS group and 42.3% in the rTMS-dTMS group, which was significantly higher than 10.5% of the drug group. We demonstrate here that both accelerated dTMS protocols significantly reduced HAMD scores, improved the response rates, and remission rates, outperforming pharmacotherapy alone. Resting-state EEG analysis further revealed unique frequency-specific functional connectivity (FC) modulation effects: the rTMS-dTMS group primarily exhibited weakened alpha-band functional connectivity within the fronto-occipital, fronto-temporal and fronto-central networks after treatment, whereas the iTBS-dTMS group predominantly demonstrated reduced theta-band functional connectivity within the fronto-parietal, fronto-occipital and fronto-temporal pathways after treatment. These findings indicate that iTBS of accelerated dTMS demonstrates comparable efficacy and tolerability to 18-Hz rTMS of accelerated dTMS, whilst inducing treatment-specific network-level neurophysiological alterations. In the rTMS-dTMS group, relative changes in FC between the frontal and temporal/precentral regions showed significant negative correlation with HAMD score reduction rates, while relative changes in FC between the frontal lobe and parietal lobe showed a significant positive correlation with the rate of HAMD score reduction for the iTBS-dTMS group. This study revealed novel mechanisms by which accelerated dTMS protocols modulate brain networks, providing evidence for the clinical application of accelerated iTBS-dTMS as an efficient, evidence-based treatment for MDD.

Humans↗

PubMed2026

Adaptive deletion of functional duplicate genes in Drosophila.

Gene deletion is traditionally viewed as a nonadaptive mechanism that eliminates functional redundancy, yet emerging evidence indicates that it disproportionately affects tissue-specific duplicates with unique functions. Here, we test whether gene deletion preferentially removes weakly constrained, degenerating duplicates or instead eliminates functionally active duplicates through an adaptive process. To identify the evolutionary and functional factors that determine which duplicates are lost, we systematically analyzed 100 gene deletion events in Drosophila by integrating sequence, expression, interaction, and structural data. We uncovered a strong bias toward the loss of younger child copies among functionally unique duplicates, whereas no such bias was observed for redundant duplicates. Contrary to expectations under relaxed constraint, deleted functionally unique genes evolve more slowly, show higher expression, engage in more protein-protein interactions, and do not exhibit elevated structural divergence or intrinsic disorder relative to redundant duplicates. When compared with single-copy genes, deleted functionally unique genes display similar evolutionary rates, slightly lower expression, greater network connectivity, comparable structural divergence, and lower intrinsic disorder. These patterns suggest that deletion frequently affects functionally active rather than degenerate genes. Collectively, our results support the hypothesis that gene deletion in Drosophila can represent an adaptive process acting on transiently functional duplicates, potentially driven by either genome streamlining or context-dependent deleterious effects.

evolution↗

PubMed2026

Electroencephalographic evidence of cortical network disruption preceding overt cardioinhibition during tilt-induced reflex syncope.

OBJECTIVE: Reflex syncope is a common cause of transient loss of consciousness. However, the early cerebral mechanisms underlying cardiovascular changes remain poorly understood. Our objective was to investigate early cerebral changes by quantitatively analyzing EEG activity preceding overt cardioinhibition during tilt-induced reflex syncope. METHODS: EEG recordings from patients undergoing tilt testing were retrospectively analyzed. Patients who experienced reflex syncope were compared to those who did not. Spectral and functional connectivity analyses were performed across baseline, pre-cardioinhibition, and syncopal phases. RESULTS: Prior to the onset of cardioinhibitory pathological reflex, a significant increase in theta-band spectral power was observed in the right temporal region, accompanied by a widespread increase in functional connectivity within the same frequency band. These findings suggest the involvement of brain networks before cardioinhibition. CONCLUSIONS: EEG changes in the theta band (power and functional connectivity) were observed before overt cardioinhibition during tilt-induced reflex syncope. SIGNIFICANCE: Our findings support the hypothesis of cortical processing preceding cardioinhibition in reflex syncope. EEG may represent a valuable complementary tool for improving the understanding and diagnosis of these events.

Humans↗

PubMed2026

Continuous theta-burst stimulation over the right DLPFC modulates central executive network connectivity in depression: exploratory analysis of a randomized clinical trial.

Previous studies suggest that transcranial magnetic stimulation exerts antidepressant effects and is associated with alterations in functional connectivity (FC), but the neural correlates remain unclear. This exploratory sham-controlled trial investigated the effect of continuous theta-burst stimulation (cTBS) over the right dorsolateral prefrontal cortex (DLPFC) on FC in major depressive disorder (MDD). Seventy MDD patients were randomized to receive two-week treatment of personalized cTBS or sham stimulation. Resting-state fMRI was performed at baseline and post-treatment. Ultimately, 31 patients in the active cTBS group and 28 patients in the sham group passed imaging quality control and were included in the final analysis. To identify the FC that may have been influenced by cTBS treatment, two complementary FC analyses were conducted: (1) voxel-wise degree centrality (DC) followed by seed-based FC, and (2) an individual FC analysis based on the stimulation targets. Furthermore, correlations between FC changes and clinical symptoms improvement were examined. Both groups exhibited reductions of depression scores, with greater improvement in the active group. Compared to the sham group, active cTBS showed increased DC in the precuneus and elevated FC between the precuneus (within the para-cingulate network) and the right inferior parietal lobule (IPL) and DLPFC. Further stimulation target-based analysis revealed increased FC between stimulation targets and both the precuneus and visual regions following treatment. Our findings reveal neural changes associated with cTBS over the right DLPFC in MDD, notably involving the precuneus and its connectivity with the right IPL/DLPFC, suggesting alterations within the central executive network. TRIAL REGISTRATION: chictr.org.cn; ChiCTR2300068273.

Humans↗

PubMed2026

Network oscillatory dynamics accompany cerebral bioenergetic defence in hypoxia.

A network physiology framework investigated how coordinated interactions among multiple organ systems collectively support the preservation of cerebral bioenergetic function and better distinguish adaptive from maladaptive responses to hypoxia. Twelve healthy males were passively exposed to 6 h of normoxia (21% O2) and hypoxia (12% O2) in a randomised, single-blind, crossover design. Venous blood was assayed for oxidative-nitrosative stress (OXNOS, spectroscopy/chemiluminescence) and neurovascular unit (hs-ELISA) biomarkers. Global cerebral delivery of O2 and glucose were determined by duplex ultrasound. Clinical acute mountain sickness (AMS+) was diagnosed in five participants. Cerebral substrate delivery was well maintained in both hypoxia and AMS+ (p < 0.05 vs normoxia and AMS-) despite marked arterial hypoxemia. Bioenergetic defence coincided with pronounced elevations in the spectral amplitude and phase synchronisation of very low-frequency oscillations (VLFOs, 0.03-0.06 Hz), which were evident across multiple organ systems and most prominent within the cerebral network. Systemic VLFOs were further exaggerated and more functionally connected in AMS+ in the absence of exaggerated systemic OXNOS or structural damage/destabilisation of the neurovascular unit (both p < 0.05 vs normoxia and AMS-). Collectively, these findings suggest that AMS, while characterised by debilitating symptomatology, may reflect a neuroprotective adaptive as opposed to pathologically maladaptive phenotype.

Humans↗

PubMed2026

Profilin promotes lamellipodium protrusion by tuning the antagonistic activities of capping protein and VASP.

Cell migration frequently employs protrusions termed lamellipodia, constituting the prime model system for generation of branched actin filament networks. Here we utilize genome editing to explore the functional connections between the actin monomer-binding protein profilin (Pfn), the filament nucleating Arp2/3 complex, its co-factor heterodimeric capping protein (CP) and Ena/VASP family polymerases in lamellipodial actin assembly. We show that Pfn counters Ena/VASP but promotes Arp2/3 complex activity, while Ena/VASP and CP mutually antagonize each other. While Pfn promotes Arp2/3 complex activity irrespective of Ena/VASP, sensitivity of CP to Pfn removal vanishes in the absence of Ena/VASP. Our findings establish Pfn as master regulator of Arp2/3 complex-dependent actin network formation, differentially regulating VASP and its antagonizer CP. Mathematical modeling of our data suggest Ena/VASP and CP to compete for recruitment to lamellipodial edges. Our work provides critical insights into the molecular logic of branched actin network assembly in protrusion and force generation.

Profilins↗

PubMed2026

Genome-Wide Characterization of β-Glucosidase (TaBGLU) Genes in Bread Wheat and Their Expression Under Drought, Cold, and Combined Stress.

Glycoside hydrolase 1 (GH1) β-glucosidases were known to activate hormone conjugates and defense metabolites, yet their genomic organization and stress-response dynamics in wheat remained incompletely defined. We therefore performed an integrated characterization of TaBGLUs spanning phylogeny, gene structure and conserved motifs, subcellular localization, promoter cis-elements, Gene Ontology enrichment, protein-protein interaction networks, and targeted expression profiling. Wheat TaBGLUs partitioned into well-supported clades that shared canonical GH1 catalytic residues and a largely conserved motif scaffold. Subcellular localization predictions indicated predominant nuclear and chloroplast targeting, with a smaller cohort directed to secretory or endomembrane compartments. Promoters were enriched for light-responsive, hormone-related (ABA, JA/SA, auxin, GA) and stress-associated (MYB/WRKY, heat, low temperature) cis-elements, and functional annotations were consistent with roles in carbohydrate and cell-wall metabolism, hormone homeostasis, and defense. Network analysis revealed a densely connected TaBGLU submodule embedded within broader carbohydrate and defense interaction networks, suggesting coordinated or cooperative functions. Expression profiling under cold, drought, and combined drought and cold demonstrated broad stress inducibility, with early activation detected by 6 h, cold-responsive maxima typically at 12 h, drought-responsive peaks predominating at 24 h, and combined stress eliciting both earlier and more sustained expression maxima between 12-24 h. Representative strongly responsive genes included TaBGLU20, TaBGLU44, TaBGLU6, and TaBGLU23, which showed pronounced late induction under combined stress, TaBGLU30, which exhibited an earlier combined-stress peak, and TaBGLU12, which displayed a marked late drought-specific response. Taken together, this integrated genomic, regulatory, and expression atlas refined the wheat BGLU repertoire relative to previous gene model inventories, highlighted candidate TaBGLUs with central network positions and strong stress inducibility, and provided concrete entry points for functional validation and breeding for improved stress resilience.

Triticum↗

PubMed2026

GiGCN: a network-based framework for uncovering synthetic lethal and viable genetic interactions.

Genetic interactions (GIs) underpin the functional connectivity of genes and pathways, and are important for dissecting genotype-phenotype relationships and identifying therapeutic targets for diseases. However, the scale of the human genome restricts systematic experimental interrogation of GIs. Existing computational tools focus on predicting synthetic lethality (SL) and synthetic viability (SV), the two primary forms of GIs, yet their accuracy and biological interpretability are compromised by inadequate modeling of the molecular mechanisms behind positive and negative interactions, as well as the limitation of negative samples. To overcome these challenges, we developed Genetic Interaction Graph Convolutional Network (GiGCN), a signed network modeling framework for the joint identification of gene pairs with SL and SV. We built a high-confidence signed genetic network by integrating verified GIs, and non-interacting gene pairs, together with gene semantic similarity derived from biological processes. By leveraging disentangled subspace decomposition, this framework separately models distinct functional dimensions within gene networks, enabling robust representation of context-dependent regulatory relationships and accurate discrimination of SL and SV events. Benchmark experiments demonstrate that GiGCN outperforms state-of-the-art approaches (area under receiver operating-characteristic curve: 0.978, and area under precision-recall curve: 0.944). Further analyses reveal biologically meaningful insights, including known and novel SL interactions centered on the oncogene MYC Proto-Oncogene (MYC), as well as SV interactions linked to autophagy and mitophagy pathways. This study provides a robust and interpretable network-based strategy for systematically exploring GIs. The GiGCN framework not only improves the precision of SL and SV prediction, but also offers mechanistic insights into gene functional relationships, thereby supporting the discovery of actionable therapeutic targets for cancer and other human diseases.

Humans↗