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Results for “animal behavior and cognition”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2026

Sensory neuron dysfunction and hyperexcitability in dorsal root ganglia at disease onset in the SOD1G93A mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder traditionally characterized by motor neuron degeneration, but emerging evidence indicates sensory system involvement. Despite reports of sensory abnormalities in some patients, the molecular and functional alterations in dorsal root ganglion (DRG) neurons remain insufficiently characterized. We investigated DRG pathology at disease onset in 12-week-old SOD1G93A mice using an integrated transcriptomic, morphological, and electrophysiological approach. RNA sequencing of lumbar DRG identified 35 differentially expressed genes, predominantly upregulated, enriched in oxidative stress-related and phagosome pathways. Comparative analysis with motor neuron transcriptomes revealed distinct gene expression profiles, indicating sensory neuron-specific molecular responses. Immunohistochemistry demonstrated reduced soma diameter in both A- and C-fiber DRG neurons. Nav channel colocalization increased for Nav1.7 in A fibers and Nav1.8 in both fiber types, whereas Nav1.6 was unchanged. Whole-cell patch-clamp recordings showed depolarized resting membrane potential, increased spike amplitude, and enhanced repetitive firing in A-fiber neurons, consistent with hyperexcitability, while C fibers showed no significant functional changes. These findings demonstrate early molecular, structural, and functional alterations in primary sensory neurons in ALS, supporting pathology beyond motor neurons and identifying sensory neuron excitability as a potential therapeutic target.

neuroscience↗

bioRxiv2026

Cas12a cleavage and trimming kinetics reveal mismatches as a tool to steer editing

Gene knockouts by CRISPR-Cas nucleases rely on targeted DNA cleavage and error-prone DNA repair: end-joining pathways can introduce insertions and deletions that assist in disrupting the coding sequence. However, only a fraction of edits achieves this, and an unfavorable array of repair outcomes typically requires switching to another editing technology. Key factors that influence repair are the types and lengths of DNA ends following cleavage. Here, we investigated Cas12a's ability to produce different ends and if they can be used to redistribute editing outcomes. We determined the sites and rates of target cleavage by Cas12a in vitro by combining kinetic modeling with nucleotide-resolution assays. For the first time, we show that trimming - repeated cleavage of an already cut target - occurs about 4x faster than initial cleavage; it also presents alternative DNA end structures for cellular repair. We next introduced specific mismatches to the gRNA. Cas12a maintained fast target cleavage, but changed where the target was cleaved and how quickly it was trimmed, compared to matched gRNA. We exploited the differences in cleavage dynamics between matched and mismatched gRNAs to develop reprogrammed gRNAs, i.e. rpgRNAs. Intentionally-mismatched rpgRNAs retained the high editing efficiency observed with traditional gRNAs. However, they redirected editing between in-frame and out-of-frame outcomes to enhance gene knockout success across genes. Reprogrammed gRNAs offer an efficient way to steer editing toward such preferred outcomes, while retaining the simplicity of gene editing with CRISPR-Cas nucleases.

biochemistry↗

bioRxiv2026

POU2AF2/OCA-T1 coactivates POU2F2 and defines a lineage-specific dependency in diffuse large B-cell lymphoma

Lineage-restricted transcriptional programs establish cell identity and can create selective dependencies in cancer. Here, we identify POU2AF2, encoding the transcriptional co-activator OCA-T1, as a critical lineage-specific dependency in a subset of diffuse large B-cell lymphoma (DLBCL). Pan-cancer dependency analyses and patient cohorts reveal elevated POU2AF2 expression in genetically aggressive DLBCL, where its depletion markedly suppresses tumor growth in vitro and in vivo. Mechanistically, POU2AF2 cooperates with the B-cell lineage-defining transcription factor POU2F2 (OCT2) to activate lymphocyte activation gene programs through direct chromatin engagement, thereby sustaining malignant transcriptional networks. We further identified a key epigenetic regulatory axis composed of the lineage-specific transcription factor TCF3 and the histone methyltransferase SET1A-COMPASS that drives POU2AF2 expression downstream of B-cell receptor signaling. Single-cell transcriptomic analysis reveals that POU2AF2 marks and sustains an innate-like B1 B-cell population in vivo, a candidate cell of origin for lymphoma. Together, these findings define a lineage-restricted POU2AF2/POU2F2 transcriptional module, controlled by a TCF3/SET1A epigenetic network, that sustains both innate-like B-cell identity and malignant fitness in DLBCL. Our study uncovers a previously unrecognized lineage-specific transcriptional dependency and highlights POU2AF2 and its associated regulatory circuitry as potential therapeutic targets in aggressive B-cell malignancies.

cell biology↗

bioRxiv2026

Azithromycin Derivatives to Mitigate Off-Target Inhibition of Autophagy and Retain Beneficial Host Directed Effects

Azithromycin (AZM) is central for the treatment of chronic respiratory diseases (CRD) but has divergent off-target effects. We synthesised AZM Derivatives 1 and 2 (D1/D2) that were predicted to permit autophagy and preserve AZM's anti-inflammatory effect. The 16HBE14o- airway epithelial cell model was exposed to AZM, D1 and D2 for 16 h and assessed for autophagy flux via LC3B-II:p62/SQSTM1 abundance (Western blot). Necrosis was quantified via lactate dehydrogenase release. Inflammation (IL-6 secretion) was assessed in the THP-1 macrophage model exposed to 10 ng/mL lipopolysaccharide vs co-treatment with AZM and the derivatives for 18 h. AZM-derivative antibacterial activity (vs AZM) was determined via the minimum inhibition concentration (MIC) method using methicillin sensitive Staphylococcus aureus (MSSA). Autophagy (LC3B-II and p62/SQSTM1 abundance) was not altered by the two derivatives and was indistinguishable from the control exposure (P> 0.05 for D1 and D2, each 10 and 50 ug/mL, vs control). D2 elicited a significant decrease in LPS-induced IL-6 secretion vs the LPS-only exposure (58.22 pg/ml, n=3, 95% +/- CI [6.521-109.9]). Importantly, D2 caused a similar reduction in LPS-induced IL-6 secretion, as observed for AZM (-10.30 pg/mL, n=3, 95% CI [-62.00 to 41.39]). The MIC of AZM for MSSA growth was 0.5 ug/ml, where as D1 and D2 were 1.0 and 8.0 ug/mL, respectively (P<0.05). We show for the first time that AZM can be redesigned to mitigate its potent arrest of autophagy while preserving its anti-inflammatory activity, to counter the generation of further AZM resistant strains.

cell biology↗

bioRxiv2026

PGM3 inhibition rewires RUVBL2-dependent DNA repair and induces a BRCAness-like state in pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) exhibits profound metabolic rewiring and strong resistance to DNA-damaging therapies, yet how metabolic pathways regulate genome maintenance remains poorly understood. The hexosamine biosynthetic pathway (HBP) integrates nutrient availability with protein glycosylation through production of UDP-GlcNAc, but its role in DNA damage response (DDR) regulation is unclear. Here we show that inhibition of the HBP enzyme phosphoglucomutase-3 (PGM3) reduces DNA repair capacity in pancreatic cancer cells. Transcriptomic and functional analyses reveal that the selective PGM3 inhibitor FR054 amplifies gemcitabine-induced replication stress, disrupts ATR-CHK1 and ATM-CHK2 checkpoint signaling, and selectively impairs homologous recombination. Glycoproteomic profiling identifies the AAA+ ATPase RUVBL2 as a key metabolic-DDR node. Gemcitabine increases RUVBL2 O-GlcNAcylation, with Thr81 identified as a modified residue within the Walker A nucleotide-binding motif. Structural modelling predicts that Thr81 O-GlcNAcylation stabilizes the RUVBL1-RUVBL2 complex without compromising ATP-Mg engagement. PGM3 inhibition and Thr81 mutation similarly reduced ATR and ATM abundance and promoted persistent DNA damage, supporting a role for RUVBL2 Thr81 O-GlcNAcylation in sustaining checkpoint signalling and genome stability. Consequently, PGM3 inhibition induces a BRCAness-like state that sensitizes pancreatic cancer cells to PARP inhibition, both in vitro and in vivo, as well as to ionizing radiation. These findings reveal a nutrient-sensitive mechanism linking protein glycosylation to genome maintenance and identify HBP-dependent DNA repair as a potentially actionable vulnerability in pancreatic cancer.

cancer biology↗

bioRxiv2026

Dog-wise canine gut metagenome assemblies with reconstructed bacterial genomes and viral candidates

Long-read metagenomic sequencing can improve genome recovery from complex gut microbial communities, yet directly reusable canine gut genome resources remain limited. Here we describe DogMAG, a canine gut metagenome resource based on dog-wise long-read and hybrid assemblies generated by grouping sequencing libraries according to canonical dog identity before assembly. The final dataset comprises 41 assemblies linked to 277 FASTQ records, including 30 Flye long-read-only and 11 OPERA-MS hybrid assemblies. A single integrated BASALT workflow produced 11,276 selected bin/version records, followed by explicit quality-based re-selection of 3,418 medium-quality-or-better metagenome-assembled genome candidates. External dRep dereplication yielded 792 strain-like representatives at 99% average nucleotide identity and 135 species/SGB-like representatives at 95%. GTDB-Tk classified all 792 representatives as Bacteria. Viral screening identified 22,068 geNomad predictions, of which 3,374 Complete, High-quality or Medium-quality viral/proviral candidate rows passed CheckV filtering with contamination [≤]10%. DogMAG provides assemblies, genome and viral candidate sequences, metadata, provenance tables and workflow scripts for reuse, benchmarking and reanalysis.

microbiology↗

bioRxiv2026

Tau isoforms modulate the axon initial segment controlling axonal trafficking and neuronal excitability

The axon initial segment (AIS) is a specialized neuronal compartment integrating action potential initiation with selective control of axonal trafficking. The microtubule associated protein tau is a central regulator of cytoskeletal organization and transport, yet how distinct tau isoforms contribute to AIS development and function remains unclear. Here, we examined the role of tau isoform relative abundance in regulating AIS establishment, maturation, excitability, and transport selectivity using murine primary neurons and human induced pluripotent stem cell (hiPSC)-derived neurons combined with super resolution imaging, electrophysiology, and live trafficking assays. We found that tau expression levels and isoform content modulate the timing and robustness of AIS maturation. In murine neurons, tau deficiency or predominance of 3 repeat (3R) tau delays Ankyrin G accumulation and AIS stabilization without preventing AIS formation. hiPSC-derived neurons display an intrinsic AIS developmental program accompanied by progressive changes in tau isoform content. Super resolution DNA PAINT reveals that endogenous tau decorates axonal microtubules in discrete nanoclusters with compartment specific distributions. Modulation of the endogenous 3R/4R tau balance in hiPSC-derived neurons shows that isoform composition, independently of tau levels, regulates AIS positioning and Ankyrin G organization. Functionally, shifts towards 3R-tau reduce sodium currents, impair action potential firing, and alter lysosomal transport dynamics within the AIS. Together, these findings identify tau isoform balance as a developmental regulator of AIS maturation, linking cytoskeletal organization to neuronal excitability and transport gating. Because the aberrant alternative tau splicing of exon 10 is a defining feature of primary tauopathies, our results provide mechanistic insight into how imbalanced tau isoforms may contribute to neuronal dysfunction.

cell biology↗

bioRxiv2026

Multiscale modelling of drug-host-pathogen interaction: quantifying drug and immune contributions to treatment response

Background and Objective: Predicting treatment outcomes in infectious diseases requires accounting for the interplay between drug effects, pathogen dynamics, and host immunity. Integrating pharmacological and immunological approaches into a single simulation environment remains a fundamental challenge in both theory and practice. We aimed to develop and validate a multiscale in silico framework coupling these processes, and to quantify their respective contributions to bacterial clearance. Methods: We present the Drug-Host-Pathogen Interaction (DHPI) framework, combining three independent mechanistic components: a physiologically based pharmacokinetic model of drug disposition, a pharmacokinetic-pharmacodynamic model of drug-induced bacterial killing, and a stochastic agent-based model of the immune response. Continuous concentration profiles are time-averaged onto the agent-based time grid, assigned to bacterial phenotypic states, and converted into per-agent killing probabilities, so that drug-mediated and immune-mediated death events are recorded separately at each step. The framework was applied to simulate symptomatic pulmonary tuberculosis. Phenotype-specific drug-efficacy parameters were inferred using Approximate Bayesian Computation from historical clinical data on eight weeks of 600 mg rifampicin monotherapy, and validated against independent early bactericidal activity data over a disjoint time window. Results: The calibrated framework reproduced the observed decline in bacterial load, and matched reported early bactericidal activity over the first week. In a virtual cohort of symptomatic patients, drug-mediated killing accounted for 81-88% and immune-mediated killing for 12-19% of total bacterial elimination over the 60-day treatment course, while the dormant, granuloma-contained fraction rose from 0.20-0.29 in the first week to 0.85-0.89 at treatment completion. Over a follow-up of up to 50 years, patients reaching clinical cure had accumulated more memory lymphocytes during treatment than those progressing to clinical failure or death; moreover, the final outcome depended on the immune changes occurring during therapy rather than on the initial disease stage. Conclusions: The results show that the DHPI framework can reproduce treatment dynamics observed in patients and enable the analysis of how therapy reshapes host immune responses and subsequent disease trajectories. By explicitly representing drug-host-pathogen interactions, it provides a mechanistic basis for in silico treatment simulations and for the study of long-term immune consequences of antimicrobial therapy.

systems biology↗

bioRxiv2026

Structural basis for tetraspanin-dependent surface export and adhesive function of integrin α3β1

Integrin 3{beta}1 (ITG3{beta}1) is a member of an integrin subfamily that binds to laminin proteins and promotes attachment of epithelial cells to the basement membrane. ITG3{beta}1 forms a complex with the tetraspanin CD151, and loss-of-function mutations in both ITG3 and CD151 cause epidermolysis bullosa, a severe skin blistering disease resulting from a defect in basement membrane attachment. Here, we report the cryoEM structure of an ITG3{beta}1 complex with CD151 and show that mutation of CD151 at the binding interface disrupts complex formation in cells. Strikingly, CRISPR-mediated knockout of CD151 leads to a variably penetrant ITG3{beta}1 surface export defect that is restored by re-expression of wild-type but not interface-mutated CD151. Together, these studies define the molecular basis for binding of CD151 to ITG3{beta}1, and show that CD151 promotes ITG3{beta}1 surface export, providing a biochemical explanation for the CD151 loss-of-function phenotype in epidermolysis bullosa.

biochemistry↗

bioRxiv2026

Cell-type separability predicts annotation accuracy and outweighs algorithm choice: a factorial benchmark across seven scRNA paradigms

Automated cell-type annotation is a prerequisite for most single-cell RNA-sequencing (scRNA-seq) analyses, but the rapid proliferation of methods spanning marker-based, correlation-based, classical machine-learning, deep-learning, semi-supervised, large-language-model (LLM), and transformer foundation-model paradigms has outpaced head-to-head evaluation. Existing benchmarks rely on convenience samples of real datasets in which cell count, class imbalance, cell-type number, and differential-expression strength co-vary uncontrollably, precluding causal attribution of performance to any dataset property. To resolve this, we benchmarked 63 tools across seven paradigms using a Taguchi L9(34) orthogonal array that varies four dataset properties independently, progressively reconfiguring experimental control across five phases: fully controlled simulation, within-platform and cross-platform real-data validation, database-connected and LLM-based annotation under ontology-aware scoring, and fine-tuned foundation models. Using standardized oracle inputs and Cohen's {kappa}, we found that, within the ranges tested, the major paradigms achieved comparable accuracy. Accuracy was predicted near-linearly by the separability of cell types in a shared expression embedding, measured as k-nearest-neighbor (kNN) purity, a relationship that held across sequencing platforms and in fine-tuned foundation models. We attributed the vast majority of {kappa} variance to dataset structure and only a small share to tool identity. Computational cost traded against workflow accessibility rather than accuracy: accessible correlation-based and LLM-based approaches performed competitively, while foundation models matched them only after fine-tuning. Because our oracle design isolates algorithmic capability from upstream noise, these results reframe how methods should be selected: the field's near-term gains lie in strengthening infrastructure--prioritizing tool accessibility, standardized evaluation, and robustness to pipeline variation.

bioinformatics↗

bioRxiv2026

Lipogenic gene expression and substrate sensitivity in the bovine mammary gland shape milk fat composition

Milk fat is produced by mammary epithelial cells (MEC) through a conserved mechanism shared among all fat-producing cells across biological kingdoms. Although highly conserved, different tissues and organisms produce distinctive fat compositions. Notably, ruminant milk fat is characterized by enrichment in short and medium chain fatty acids. We hypothesized that this unique profile is driven by MEC-specific metabolic characteristics related to their response to lipogenic substrates. To study this, we compared bovine MEC and udder-derived fibroblasts in terms of their lipogenic capacity and fatty acid composition when exposed to lipogenic building blocks. When exposed to acetate, MEC showed coordinated upregulation of acyl-CoA short-chain synthetase 1 (ACSS1) and diacylglycerol transferase (DGAT), while expression of acyl-CoA synthetase long-chain 1 (ACSL1) decreased. Medium chain fatty acids were also elevated in acetate-treated MEC and not in fibroblasts. The role of ACSS1 in the production of medium chain fatty acids in MEC was confirmed by knockdown experiments. Metabolomics analysis showed that in MEC acetate treatment triggered a broad metabolic response, primarily amino acids catabolism, energy and polar lipid metabolism. Collectively, these findings demonstrate effective utilization of acetate for de novo fatty acid synthesis in MEC with preferred tendency to produce medium chain fatty acids.

cell biology↗

bioRxiv2026

Novel Dissymmetric Ionizable Lipid-Assembled Lipid Nanoparticles for Delivery of Ferroptosis-Related siRNA in Diabetic Treatment

Small interfering RNA (siRNA) enables precise post-transcriptional gene silencing for refractory diseases, yet its clinical translation remains limited by the lack of safe and efficient delivery vectors. Inspired by the dissymmetric alkyl chain architecture of natural membrane phospholipids, we designed and synthesized 34 novel ionizable lipids with dissymmetric hydrophobic tails and formulated them into lipid nanoparticles (LNPs). Through systematic physicochemical and biological assessments, we established clear structure-activity relationships and identified two lead LNPs (O14-LNP, H18a-LNP) with superior endosomal escape capacity, enhanced in vivo gene silencing potency, and favorable biosafety relative to the clinical benchmark MC3-LNP. In both streptozotocin-induced and spontaneous db/db type 2 diabetes (T2D) mouse models, lead LNPs delivering ferroptosis-related siRNAs effectively ameliorated glucose and lipid metabolic disorders, restored islet function, and alleviated hepatic steatosis. This study not only lays a theoretical foundation for the rational design of novel ionizable lipids, but also validates the therapeutic potential of siRNA therapy targeting ferroptosis, providing a versatile delivery platform and targeted therapeutic strategy for the treatment of T2D.

pharmacology and toxicology↗

bioRxiv2026

Melanin Suppresses Aβ Aggregation and Toxicity

The aggregation of amyloid-{beta} (A{beta}) peptides into insoluble deposits is a characteristic hallmark of Alzheimer's disease (AD) and related neurodegenerative disorders. While AD is the most common cause of dementia, there are currently no disease-modifying treatments which are both affordable and adverse-free. In this study, we report that melanin, a pigment which is commonly found in nature and is abundant in parts of the human brain, suppresses the aggregation of the 42-amino acid A{beta} variant (A{beta}42). Using biophysical and biochemical techniques, we show that melanin delays A{beta}42 aggregation while also reducing the amount of A{beta}42 that converts into aggregates. Using thioflavin T assays paired with chemical kinetics, we characterised the melanin-induced inhibition of A{beta}42 aggregation in vitro. Using MALDI-MS, we elucidate the molecular basis of this effect by showing that melanin prevents A{beta}42 dimerisation. We then demonstrate that melanin also reverts the aggregation process by dissolving pre-formed A{beta}42 fibrils. Finally, we show that melanin reduces A{beta}42 aggregation and rescues A{beta}42 toxicity in an SH-SY5Y neuroblastoma cell model. Our study shows that melanin disrupts the aggregation and cytotoxicity of A{beta}42, and suggests that compounds derived from human metabolites may offer promising avenues to combat amyloid formation.

biophysics↗

bioRxiv2026

Impaired proteostasis is an early feature of the diabetic heart in humans and mice

Diabetes and obesity increase cardiac lipid levels leading to cardiomyopathy and heart failure. We hypothesized that intermittent fasting would reduce cardiac lipid levels. Surprisingly, intermittent fasting increased myocardial triglyceride content, but rescued mortality and attenuated cardiomyopathy in mice overexpressing cardiomyocyte acyl-CoA synthetase 1 (MHC-ACSL1). Lipid overload caused cardiomyocyte accumulation of polyubiquitinated protein aggregates containing desmin, a scaffolding intermediate filament protein, which intermittent fasting prevented. Furthermore, intermittent fasting reversed elevated myocardial C16:0 ceramide content, and knockdown of ceramide synthase CerS5 and CerS6 reduced palmitate-induced protein aggregation, highlighting a role for C16:0 ceramides in this pathology. Conversely, impairing aggrephagy with cardiomyocyte-specific p62 ablation induced heart failure in mice fed a high-fat diet, with paradoxically reduced cardiac lipid content. Crucially, non-failing diabetic human hearts also exhibited protein aggregate pathology. Taken together, these results demonstrate that impaired proteostasis characterizes cardiomyopathy from cardiac lipid overload and identify a promising new therapeutic target for this condition.

molecular biology↗

bioRxiv2026

Spatial Mapping of the Lung Cancer Ecosystem Reveals Distinct Patterns of Intratumoral and Internodular Heterogeneity

The spatial organization of malignant and non-malignant cells within the tumor microenvironment (TME) critically influences tumor evolution and therapeutic response. However, the architecture of micro-niches remains incompletely understood. Leveraging Xenium-based spatial transcriptomics, we comprehensively mapped the spatial ecosystem of an orthotopic murine lung cancer model, identifying distinct spatial domains that form unique, organized cellular neighborhoods. These domains cluster into three major communities: (1) non-tumoral regions that recapitulate canonical normal lung structures; (2) a heterogeneous peri-tumoral region composed of spatial domains characterized by mesenchymal remodeling, active immune checkpoint signaling, and immunosuppressive myeloid populations; and (3) intra-tumoral regions that reveal marked tumor nodule heterogeneity, with unique tumor-specific domains exhibiting hallmark cancer pathways. Furthermore, our analytic approach was applicable to human lung cancer tissue. Notably, spatial domain analysis allowed us to resolve tumor nodules into multiple biologically distinct subtypes, defined by domain composition, hallmark cancer programs, and intercellular communication patterns within the TME.

cancer biology↗

bioRxiv2026

Why are fishers retaining manta and devil ray bycatch?

Increasing fishing pressure, including from small-scale fisheries, has caused declines in more than one-third of all elasmobranch species. Tackling conservation issues in small-scale fisheries requires interdisciplinary approaches due to the coastal community's interdependence on marine resources. To support inclusive policy change and fisher engagement, an understanding of the motivations driving fishers' operational choices (i.e., the retention of elasmobranch bycatch) is needed. We assess the motivational drivers behind bycatch retention of one of the slowest-growing and most vulnerable elasmobranch groups, manta and devil rays (collectively, mobulids), through a case study in India, their largest fishery in the world. We conducted a best-worst scaling survey in the fishery-intensive states of Tamil Nadu and Andhra Pradesh, which make significant contributions to mobulid landings on India's east coast. Our results suggest that fishers exhibit varied motivations for retaining mobulid bycatch across states. Financial motivation to sell mobulids for additional revenue was the most important motivator for bycatch retention in both states. In Tamil Nadu, the top three motivators were all financially driven, whereas in Andhra Pradesh, the top three motivators included both financial and non-financial attributes, such as nutritional importance and storage optimisation. As the first socio-economic study of mobulid fisheries in India, we show that motivations underlying bycatch retention decisions vary geographically and may be influenced by cultural differences between states and the socio-economic characteristics of decision makers. Based on identified fisher motivations, we provide context-specific recommendations to align conservation strategies with the values fishers derive from the mobulid fishery and encourage participation in conservation. These include subsidies for net repair to encourage mobulid release; promotion of a minimum price measure for sustainably sourced alternative species; quality improvement of target species; and increased awareness of national and international regulatory obligations (e.g., CITES, CMS, IOTC).

ecology↗

bioRxiv2026

OsPATROL1 overexpression accelerates stomatal opening to enhance photosynthetic induction and growth under fluctuating light in rice

Slow stomatal opening after increases in irradiance constrains carbon gain under fluctuating light, yet stomatal kinetics remain an underexplored target for crop improvement. Here, we investigated Oryza sativa PROTON ATPASE TRANSLOCATION CONTROL 1 (OsPATROL1), which encodes a Munc13-like protein implicated in stomatal regulation in Arabidopsis thaliana. OsPATROL1 overexpression had modest, condition-dependent effects on steady-state gas exchange and did not alter stomatal morphology or biochemical traits. In contrast, it consistently accelerated stomatal opening and photosynthetic induction, reducing the stomatal conductance time constant during induction by 41-43%. During 12 h of simulated natural fluctuating light, OsPATROL1-overexpressing plants maintained higher stomatal conductance and net CO2 assimilation rate, increasing cumulative assimilation by 8-12% while maintaining their intrinsic water-use efficiency (iWUE). Under artificial fluctuating light, overexpression alleviated growth reductions relative to steady light. Under glasshouse conditions, total biomass increased by 34-44%, accompanied by greater tiller number, root biomass, bleeding sap rate, and leaf nitrogen content. Taken together, these results indicate that OsPATROL1 overexpression accelerates stomatal opening, enhances photosynthetic induction and daytime carbon gain without compromising iWUE, and is associated with greater growth.

plant biology↗

bioRxiv2026

KAT3 Shuttling Between Neuronal Identity and Activity-Dependent Plasticity Programs Drives Large-Scale Chromatin Remodeling

Activity-dependent transcription is a central feature of neuronal plasticity. Here, we show that neuronal activation triggers genome-wide redistribution of CBP and p300 in hippocampal neurons. Upon stimulation, KAT3 cofactors relocate from super-enhancers supporting neuronal identity to enhancers associated with activity-regulated genes, accompanied by transient changes in H3K27ac, chromatin accessibility, and three-dimensional genome architecture. Mechanistically, distinct TF families control KAT3 shuttling: proneural bHLH factors such as NeuroD2 maintain cofactor occupancy at identity-associated regulatory elements, whereas AP-1 binds de novo at plasticity-associated loci. This dynamic redistribution reshapes enhancer landscapes and chromatin interactions, enabling robust activation of plasticity genes while transiently attenuating neuronal identity programs. Remarkably, FOS overexpression is sufficient to reproduce the repression of neuronal identity genes observed during stimulation. Together, our findings reveal a reversible competition between transcriptional networks governing neuronal identity and plasticity and identify KAT3 redistribution as a key mechanism coupling neuronal activity to large-scale chromatin remodeling.

neuroscience↗