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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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.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

The role of mu opioid receptors on excitatory and inhibitory neurons in the rostral ventromedial medulla in neuropathic pain

Descending projections from the brain to the spinal cord can regulate painful stimulus processing and are modulated by endogenous and exogenous opioids. We investigated the role of mu opioid receptors (MORs) in GABAergic vs. glutamatergic neurons of the rostral ventral medulla (RVM) in a mouse model of chronic neuropathic pain. We found that activating glutamatergic and GABAergic neurons in the RVM both result in antinociception [BC1.1]at baseline, but glutamatergic neurons enhance pain responses after nerve injury. [BC2.1]We then interrogated the role of RVM MOR signaling on neuropathic pain by using CRISPR/Cas9 to delete MOR in glutamatergic or GABAergic RVM neurons. We found that MOR knockout in glutamatergic and GABAergic RVM neurons precipitates early neuropathic pain onset with no effect on chronic pain intensity. These results suggest that RVM MOR signaling modulates hypersensitivity in the early phase of injury, but chronic neuropathic pain is largely independent of mu opioid receptor signaling.

neuroscience↗

bioRxiv2026

Increased activity in the somatosensory and insular cortex during the transition from acute to chronic neuropathic pain

Pathophysiological mechanisms underlying the transition from acute to chronic neuropathic pain remain incompletely understood. The somatosensory and insular cortices are key cortical components of the pain matrix. We examined changes in activation of these cortical regions during the transition from acute to chronic neuropathic pain. The right sciatic nerve was ligated in activity reporter TRAP mice using standard procedures. Mechanical allodynia was confirmed after CCI or sham surgery using von Frey monofilaments applied to the hind paws. To label active neurons, 4-hydroxytamoxifen was administered to separate cohorts at 1, 3, and 6 weeks following nerve ligation. Passive tissue clearing of brain sections and confocal imaging was used to assess active neurons. Progressive reduction of ipsilateral hind paw in CCI mice indicated mechanical allodynia development. CCI mice showed robust neuronal activation in the bilateral somatosensory and insular cortices. The somatosensory cortical activation peaked at 3 weeks post-CCI, whereas insular cortical activity increased during the transition from acute to chronic neuropathic pain. These studies revealed that CCI induced progressive mechanical allodynia and distinct temporal patterns of cortical neuronal activation, with transient peak neuronal activity in the somatosensory cortex and sustained, increasing activation in the insular cortex during acute-to-chronic pain transformation.

neuroscience↗

bioRxiv2026

Elevated hydrostatic pressure modulates endothelial junctional mechanotransduction through VE-cadherin remodelling and altered association with YAP1, EPS8: an endothelium-on-chip study

Endothelial dysfunction is a hallmark of numerous vascular pathologies and is strongly influenced by mechanobiological forces within the vascular microenvironment. While the effects of shear stress have been extensively investigated, the mechanisms by which elevated hydrostatic pressure regulates endothelial junctional organisation remain sparsely investigated. Here, we employed a microfluidic platform to investigate the combined effects of low shear stress (1.4 dyne/cm2) and elevated hydrostatic pressure (~3972 Pa) on endothelial junctional dynamics. Elevated hydrostatic pressure induced marked remodelling of VE-cadherin junctions, characterised by formation of serrated, finger-like structures accompanied by increased YAP1 nuclear localisation and reduced YAP1-VE-cadherin cytoplasmic colocalisation compared to shear stress alone conditions. Further, elevated hydrostatic pressure also demonstrated an increase in cytoplasmic accumulation of EPS8, an actin adaptor protein, and increased cytoplasmic EPS8-VE-cadherin colocalisation. These observations were accompanied by functional changes marked by increased endothelial permeability, and enhanced THP-1 monocyte adhesion, thus suggesting activation of mechanosensitive pathways linked to dynamic junctional reorganisation. Inhibition of PI3K at elevated hydrostatic pressure exhibited a thin VE-cadherin patterning and increased cytoplasmic EPS8-VE-cadherin colocalisation, thus demonstrating a prominent role for PI3K signalling in regulating the junction organisation. Interestingly, Piezo-1 activation using Yoda1 produced context-dependent effects. Under shear stress alone, Yoda1 promoted YAP1 nuclear translocation, reduced YAP1-VE-cadherin colocalisation, increased endothelial permeability but strikingly did not impact THP-1 adhesion compared to shear stress alone conditions. In contrast, under elevated hydrostatic pressure conditions, Yoda1 significantly reduced both endothelial permeability and THP-1 adhesion while increasing YAP1-VE-cadherin colocalisation and decreasing YAP1 nuclear accumulation. Collectively, these findings identify a previously underappreciated elevated hydrostatic pressure-Piezo-1-PI3K signalling axis that regulates endothelial barrier integrity and pro-adhesive endothelial activation through coordinated regulation of VE-cadherin, YAP1, and EPS8. These results highlight elevated hydrostatic pressure as a unique mechanobiological stimulus, distinct from that of shear stress alone and provide novel insights into mechanisms underlying microvascular dysfunction.

bioengineering↗

bioRxiv2026

DNA Damage and Repair Mechanisms in Duckweed (Spirodela polyrhiza) Under Ultraviolet-B (UV-B) Light Stress

Exposure to Ultraviolet-B (UV-B) light can adversely affect plant growth and cellular integrity by inducing oxidative stress and DNA damage. In this study, we investigated UV-B-induced DNA damage and repair responses in the aquatic monocotyledonous plant species Spirodela polyrhiza (duckweed). We exposed 13-day-old duckweed plantlets to broadband UV-B light for 1-10 min, followed by recovery periods of up to 24 h under normal growth conditions. We observed progressive chlorosis, wilting, and diminished plant vigor with longer durations of UV-B light exposure. Agarose gel electrophoresis demonstrated compromised genomic DNA integrity immediately after UV-B light treatment, with partial restoration of DNA quality during recovery. Immuno-slot blot assays established the accumulation of two major UV light-induced photoproducts, cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidone photoproducts [(6-4)PPs], in a dose-dependent manner following UV-B light exposure. Notably, the abundance of these DNA lesions declined substantially after recovery, indicating activation of endogenous DNA repair mechanisms. Staining with 3,3-diaminobenzidine revealed elevated accumulation of hydrogen peroxide immediately following UV-B exposure, suggesting enhanced oxidative stress. Collectively, these findings demonstrate that S. polyrhiza possesses efficient mechanisms for sensing, repairing, and mitigating DNA damage induced by oxidative stress resulting from UV-B light exposure. This study highlights the potential of duckweed as an effective model system for investigating DNA damage and repair pathways under UV-B light stress in plants.

plant biology↗

bioRxiv2026

Mitochondrial transfer mediates metabolic communication between beta cells and islet macrophages

Pancreatic islet macrophages support islet homeostasis and adapt their metabolic program in response to environmental cues, including beta cell released factors. Intercellular mitochondrial transfer is a biological process that modulates cellular responses. To test whether beta cells, which are strongly secretory, transfer mitochondria to islet macrophages, we generated mice with beta cell-specific expression of mitochondrial GFP (PhAMfloxIns1Cre). We demonstrate that beta cells transfer mitochondria to islet macrophages in vivo and in vitro. Diabetogenic stressors did not alter the frequency of mitochondrial transfer and macrophages containing beta cell-derived GFP exhibit increased protein synthesis rates. RNA-seq identified upregulation of activity-regulated cytoskeleton associated protein (Arc) in macrophages receiving beta cell-derived mitochondria, while disruption of actin cytoskeleton dynamics prevented mitochondrial transfer. Together, these findings identify mitochondrial transfer as a previously unrecognized mechanism of beta cell-macrophage communication that may contribute to islet homeostasis and immune regulation.

cell biology↗

bioRxiv2026

X-ray crystallographic fragment screening reveals novel and conformationally dynamic ligand-binding sites in Mycobacterium tuberculosis FtsZ

Tuberculosis is a leading cause of death globally due to an infectious agent. There is ongoing need for novel mechanisms to inhibit M. tuberculosis (Mtb) growth and infection to improve patient outcomes. FtsZ, a GTPase that assembles into protofilaments at the division site of a replicating cell to produce two individual cells, is an attractive target as an essential protein in bacterial cell division. Here we describe a crystallographic fragment screening campaign of MtbFtsZ. 1,070 crystals were soaked with fragments and 714 datasets were used for downstream PanDDA analysis. 149 datasets exhibited PanDDA-generated event map density to support modeling of fragment binding. 15 novel sites are described. Both the ON and the OFF conformations of FtsZ are found in the asymmetric unit. Asymmetric binding of fragments to each chain in the model is observed. These crystallographic fragment screening results additionally provide opportunities for fragment growing and merging to develop FtsZ binders into drug-like molecules or conformation specific chemical probes.

biophysics↗

bioRxiv2026

A COJEC-chemotherapy resistant model of Th-ALK(F1174L)/MYCN neuroblastoma offers insights into tumour immune evasion and development of the bone marrow metastatic niche

Multi-agent COJEC chemotherapy is the main-stay of induction treatment for patients diagnosed with high-risk neuroblastoma. However, at least 10% of patients will be primary refractory to chemotherapy and only 50% achieve 5-year overall survival. The bone marrow is the most frequent site of metastasis in these patients. Novel approaches are required to improve response rates but the inter- and intra- patient tumour heterogeneity and dynamics of the neuroblastoma immune microenvironment makes anticipation of resistance phenotypes incredibly challenging. We present here a novel immunocompetent C57 Bl/6 model of Th-ALK(F1174L)/MYCN neuroblastoma, in which spontaneous abdominal tumours are driven by expression of mutant Anaplastic Lymphoma Kinase and over-expression of Mycn in the neural crest. We have used this model to generate a personalised dosing schedule inducing COJEC-chemotherapy resistance, in which individual mice receive chemotherapy cycles dependent upon the progression of their neuroblastoma tumours. Using both single cell RNA sequencing and spatial immunophenotyping gave us extraordinary precision in our comprehensive analysis of the tumour intrinsic and microenvironmental factors associated with COJEC resistance. We found that the resistance phenotype was driven by Cdk8 upregulation in adrenergic and mesenchymal tumour cells. Infiltration of immunosuppressive myeloid-derived immune cells and remodeling of the tumour-associated stroma further contributed to COJEC resistance. In the bone marrow we observed expansion of neutrophils and evidence of NETosis associated with micro-metastatic disease. Our results further endorse the development of CDK8-targeting therapeutics for neuroblastoma patients which might boost the anti-tumour immune response. Additional studies will be required to define the roles of neutrophils and neutrophil NETosis in neuroblastoma progression and metastasis. Our C57 Bl/6 model will be pivotal in future preclinical studies of immune-modulating therapeutics.

cancer biology↗

bioRxiv2026

Structural Plasticity and Ligand Promiscuity of CYP3A4 Revealed by Cryo-EM

Cytochrome P450 3A4 (CYP3A4) metabolizes roughly half of all marketed drugs, and its inhibition can cause clinically significant drug-drug interactions. The enzyme accommodates chemically diverse ligands, making binding modes and metabolic outcomes difficult to predict. Previous X-ray crystallography efforts have leveraged a truncated construct without the N-terminal segment that tethers CYP3A4 to the membrane. Here we show that the same construct assembles into a symmetric trimer that can be resolved by cryo-EM and determine structures of both unliganded and ligand-bound CYP3A4. Multiple ligands are resolved with density consistent with several mutually exclusive conformations. Protein remodeling to reshape the binding pocket is concentrated in the F/G loop, which is poorly resolved and unmodeled in many X-ray structures. These features likely underlie the poor predictive performance of co-folding methods on this target. The routine use of cryo-EM to resolve CYP3A4 ligand-bound complexes will provide the ground truth data needed to make predictive models of drug metabolism useful in practice.

biophysics↗

bioRxiv2026

Morphologic intratumoral heterogeneity from routine whole-slide histopathology is prognostic for survival in primary central nervous system lymphoma: development in the LOC Network and international external validation

Background: Clinical scores incompletely capture outcomes in primary central nervous system lymphoma (PCNSL). We quantified morphologic heterogeneity in pretreatment hematoxylin and eosin (H\&E) whole slides. Patients and methods: Three independent cohorts of immunocompetent, HIV- and EBV-negative patients treated recently were analyzed: LOC 2023 (122 slides), phase III BLOCAGE-01 (245 slides; NCT02313389), and external Barcelona (BCN; 41 slides). UNI embeddings, prototype learning, spatial metrics, and elastic-net Cox regression defined ITH-C. Results: Models achieved bootstrap-corrected concordance of 0.797--0.834. Age-, sex-, and KPS-adjusted ITH-C HRs were 1.29 (95\% CI 1.01--1.64), 1.27 (1.07--1.51), and 2.13 (1.35--3.37), respectively. Adding ITH-C increased MSKCC C-index from 0.671 to 0.717, 0.560 to 0.593, and 0.588 to 0.706. Spatial transcriptomics linked ITH-C to immune programs. Conclusions: Routine H\&E encodes prognostic spatial heterogeneity in PCNSL. ITH-C complements clinical scores, supporting prospective risk stratification.

bioinformatics↗

bioRxiv2026

EEG Oscillations in Guided Mindfulness versus Mind-Wandering in Young Adults: Effects of Auditory Task Instruction and Naturalistic Video

Alpha and theta band EEG oscillations have been implicated in states of mindfulness meditation. However, results are inconsistent and the influence of testing environment variables is not well-characterized. We used EEG to measure the amplitude of brain oscillations in a mindful-attention versus mind-wandering condition, in which guided auditory instructions were interleaved with periods of silence, with and without accompanying naturalistic video projections. We generated precise measures of alpha and theta in a sample of 20 young-adult non-expert meditators, by identifying each participant's individual alpha peak frequency (IAF) from posterior EEG electrodes and using it to define four individualized frequency bands: two low alpha bands (in 2 Hz increments below the IAF), one upper alpha band (from IAF to 2 Hz above IAF), and one theta band (4 Hz - 6 Hz below IAF). We found that the mindfulness manipulation significantly increased power in alpha ranging between 2 Hz below to 2 Hz above IAF, including peak alpha amplitude, compared with mind-wandering. Meanwhile, central theta amplitude was larger when auditory instructions were on versus off, and naturalistic video did not reliably modulate the EEG effects of mindfulness. We conclude that the acute effects of mindfulness in non-expert meditators are most consistently observed as increases of posterior alpha-band activity, and that auditory task-instructions should be accounted for in studies of guided meditation. Observed alpha increases may reflect induced states of calm or relaxation induced by mindfulness practice, as proposed in previous studies. These results may apply to mindfulness training or biofeedback therapies.

neuroscience↗

bioRxiv2026

Stop codon readthrough in Trichomonas is a mechanism for gene expression regulation and expanding protein function

Trichomonas vaginalis is the causative agent of trichomoniasis, a common sexually transmitted infection among women of reproductive and peri-menopausal age. The parasite has an unusually large genome, rich in complex repeats, including a vast repertoire of transposable elements and multi-copy gene families. Since very few T. vaginalis genes have introns, gene expression is usually straightforward, with ribosomal translational machinery proceeding from a start codon to the next in-frame stop codon of an unspliced poly(A)denylated mRNA. However, our previous studies raised the possibility of T. vaginalis gene expression involving stop codon readthrough (SCR), where transcription through in-frame stop codons produces longer-than-predicted mRNAs that translate to fully functional proteins. Here, we leverage long-read RNA-seq and new chromosome-scale assemblies of two T. vaginalis strains and two avian sister species to investigate and characterize ~1,400 long, mature mRNAs that contain more than one predicted protein-coding gene transcribed from what we call '' RT genes '', composites of adjacent predicted genes. We first identify RT genes in a second T. vaginalis strain and in close relatives T. vaginalis-like and T. stableri, indicating that this phenomenon is conserved among Trichomonas species and strains. Second, we find transcripts of RT genes to be more abundant by many orders of magnitude than monocistronic genes. Third, we found the distance between predicted genes within RT genes to be significantly shorter than between adjacent independent predicted genes. Fourth, functional annotation revealed that RT genes encode at least 50 distinct protein functions, suggesting that this unusual transcriptional mechanism has a role in an array of biological processes in Trichomonas. Our results from two Trichomonas species suggest that SCR is an important mechanism controlling gene expression and the diversity of protein function in this parasite.

molecular biology↗

bioRxiv2026

A geometric anthropomorphic phantom for quantitative susceptibility mapping: accuracy and repeatability

Quantitative Susceptibility Mapping (QSM) relies on a tissue's underlying macroscopic geometry to lead to measurable orientation-dependent field perturbations. To understand and assess QSM error in vivo, anthropomorphic phantoms provide a useful model that mimic the electromagnetic properties and morphology of underlying tissue. Herein, we designed and manufactured an MRI compatible anthropomorphic phantom with cylindrical and spheroid compartments containing realistic susceptibilities to mimic hemorrhages, calcifications, and blood vessels. We estimated accuracy ({epsilon}, bias, RMSE) and repeatability (RC) of MEDI-susceptibility measurements within ROIs. We evaluated voxel-based agreement to validate susceptibility mapping under different acquisition conditions (3T versus 7T) and reconstruction algorithms (COSMOS versus MEDI). Reliable MEDI-based susceptibility measurements were obtained from ellipsoids but not from straws. The ellipsoids (|{epsilon}| = 0.007 to 0.083 ppm at 3T; 0.050 to 0.118 ppm at 7T) were more accurate than the straws (|{epsilon}| = 0.084 to 0.190 ppm at 3T; 0.105 to 0.160 ppm at 7T). The repeatability coefficient across all 6 ROIs (RC = 0.652 ppm at 3T; 0.459 ppm at 7T) was substantially larger than across the 4 ellipsoid ROIs only (RC' = 0.168 ppm at 3T; 0.141 ppm at 7T). The accuracy at 3T (bias = -0.002 ppm, RMSE = 0.082 ppm) was better than the accuracy at 7T (bias = -0.056 ppm, RMSE = 0.092 ppm). Using voxels from the 4 ellipsoid ROIs, we observed excellent agreement between COSMOS and MEDI susceptibility maps at 3T, with linear regression of y=1.00x-0.01 (r=0.99). We observed some underestimation of MEDI susceptibility maps relative to COSMOS at 7T, with linear regression and y=0.93x-0.04 (r=0.99). The results imply that QSM reconstructions are reliable with 3T scanners but can be challenging with 7T scanners at high magnetic susceptibilities.

biophysics↗

bioRxiv2026

Evaluating Large Language Models as Tools to Navigate Researchers in Rapidly Evolving Research Landscapes: A Case Study in Cancer Drug Response Prediction

Large Language Models (LLMs) have emerged as promising tools for assisting researchers in automating and accelerating the synthesis of literature reviews. However, their reliability is a significant concern due to issues like factual inaccuracies and hallucinations. The key question is whether LLMs can reliably provide comprehensive, up-to-date overviews and analyses. This study evaluates the performance of three leading LLMs (OpenAI's ChatGPT, Google's Gemini, and DeepSeek) on the complex task of generating a comprehensive survey paper on deep learning for cancer Drug Response Prediction (DRP). By testing both standard and Deep Research (DR) / Deep Think (DT) modes of LLMs with prompts of varying detail, this paper assesses key academic dimensions, including reference management, content quality, and analytical depth. Key findings reveal that while DR modes of LLMs significantly improve reliability by eliminating hallucinations, performance variations exist across models and prompts. A trade-off between reference quantity and integration quality was observed, and even the best-performing models lacked the analytical depth of human experts, often requiring extensive human supervision. The study concludes that LLMs currently serve as powerful assistive tools but still cannot replace the critical validation and synthesis provided by human researchers. Choosing the best LLM to use depends on the task in hand, while several strategies can be implemented to improve the produced output.

scientific communication and education↗

bioRxiv2026

Single-Cell Analytics for Dose Response (SCADR) discriminates PTEN missense variants by lipid and protein phosphatase dysfunction

The proliferation of sequencing efforts has revealed a vast and expanding catalog of single nucleotide gene variants, many associated to, but with unclear roles in disease. Fully charactering variant impacts and linking specific protein dysfunctions to disease are challenging due to the multi-functional nature of many proteins and varying degree of variant effects on these functions. Lagging are sensitive approaches to empirically assess the impact of missense variant-induced single amino acid changes on a wide range of protein functions. To address these issues, we have developed an open-source computational analysis tool called SCADR (Single-Cell Analytics for Dose Response) for simultaneously measuring and comparing impacts of exogenously-expressed variants on multiple signaling pathways using multiplex phospho-antibody spectral flow cytometry in human cell lines. SCADR retains and correlates single-cell measures of signal protein activity states along with expression levels of exogenously-expressed variants, providing rich characterization of multiple protein functions, signaling protein interactions, and enhanced discrimination of variant impacts on different signaling pathways, highlighting each variants unique dysfunction profile. Here, we apply SCADR for analyses of the impact of 6 variants of the tumor-suppressor protein PTEN (P38H, C124S, G129E, Y138L, D268E, 4A) expressed in HEK293 cells on the phosphorylation states of the canonical and noncanonical downstream signaling proteins Akt, S6, CREB, ERK, and p38 detected with fluorophore-conjugated phospho-antibodies, along with an antibody detecting an N-terminal HA tag on PTEN variants allowing measures of dose-response effects of each variants expression on signaling cascades. Results identify variant-specific impacts on downstream signaling cascades.

genomics↗

bioRxiv2026

From Prompt to Provenance: BloClaw, a Capability-Gated AI4S Workstation for Auditable Computational Biology

Scientific agents can produce plausible answers while remaining unable to establish whether the computation behind an answer is executable, recoverable, or reproducible. We present BloClaw, an AI4S workstation built around a simple principle: a scientific agent should know what it can do, show how it did it, and state what remains unvalidated. Each capability declares an execution state, input constraints, dependencies, expected outputs, and scientific limitations. Natural-language requests are translated into structured tasks, validated against this registry, executed through scientific tools, and recorded in a provenance-aware Living Lab Notebook. The system is designed to detect invalid inputs, failed tool calls, missing dependencies, and remote timeouts, and to route them to repair, retry, or escalation. The implemented and tested scope comprises RDKit-based molecular property and rule screening, protein structure analysis, docking-pose inspection, 3D visualization, and structured reporting. We demonstrate the workflow on a PubChem-retrieved osimertinib structure and a supplied 6LU7 docking artifact: the former yields deterministic descriptors (molecular weight 499.619 Da, cLogP 4.5098, TPSA 87.55 A^2), while the latter contains 2,387 protein ATOM records, 309 residues, and nine pose records. These examples are workflow demonstrations, not efficacy or affinity studies. Beyond retrospective prediction, the manuscript specifies a prior-minimized constructive mode in which a desired function is compiled into explicit physical, chemical, and systems constraints, candidate mechanisms are simulated, and observations are reintroduced for calibration and falsification; this is a proposed extension rather than a result of the present case studies. We describe an evaluation protocol that compares BloClaw with a standard single-agent workflow and fixed-script execution using task completion, scientific correctness, recovery success, provenance completeness, reproducibility, human review time, latency, and cost. This manuscript reports the system design, verified capability boundary, deterministic software artifacts, and a reproducible evaluation protocol; it does not claim benchmark improvements before those experiments are run. BloClaw is an execution and accountability layer for AI-assisted research, complementing expert review and experimental validation rather than replacing them.

bioinformatics↗

bioRxiv2026

Melanophilin, a Myosin Va Adapter Protein, Biases Track Selection of Myosin Va-and Kinesin-1-Transported Liposomes at Actin-Microtubule Intersections In Vitro

Secretory vesicle transport from the Golgi to the cell membrane involves kinesin and myosin Va motors on the vesicle surface cooperatively navigating their shared cargo through numerous actin-microtubule (MT) intersections. How the track on which the cargo exits the intersection is selected so that vesicles are delivered to their destination with spatial and temporal fidelity remains unclear. Here we hypothesized that melanophilin -- the adapter that links myosin Va to pigmented melanosomes and can bind to both actin and MTs -- acts as a phosphorylation-dependent switch to bias track preference at actin-MT intersections. To test this, we modeled melanosome transport in vitro using 350-nm liposomes with ~5 surface-bound molecules each of constitutively active myosin Va, kinesin-1, and full-length melanophilin with varying phosphorylation levels. Liposomes were then challenged with actin-MT intersections. Regardless of the track the liposomes entered the intersection on, liposomes with phosphorylated melanophilin were biased towards exiting the intersection on actin filaments while those with dephosphorylated melanophilin were biased to exit on MTs. Consistent with this, phosphorylated melanophilin showed a 2-fold preference to bind actin over MTs, and slowed liposome transport by myosin Va along actin filaments by ~40% by effectively acting as an anchor. Conversely, dephosphorylated melanophilin preferentially bound (2-fold) MTs over actin and, by acting as a tether, increased the kinesin-1 liposome transport distance on MTs. Therefore, melanophilin, based on its phosphorylation state, can bias track selection of cargo transported by kinesin-1 and myosin Va through the cell's complex cytoskeletal network with its numerous actin-MT intersections.

biophysics↗

bioRxiv2026

Heterogeneous and conserved radiation responses reveal FOXM1-dependent regulation of microcephaly genes in glioblastoma

Glioblastoma (GBM) is characterized by marked heterogeneity, glioma stem-like cells (GSCs), and resistance to therapy. Because GSCs share features with neural progenitor cells (NPCs), we investigated whether neurodevelopmental programs contribute to their response to irradiation. Transcriptional profiling of four patient-derived GSC lines revealed cell line-specific responses, with radiosensitivity correlating with the magnitude of p53 activation and basal expression of its negative regulator, MDM2. Despite this heterogeneity, radiation consistently activated p53-dependent pathways and suppressed cell-cycle programs. Among these, genes associated with primary hereditary microcephaly (MCPH) that regulate NPC proliferation were coordinately repressed. Single-cell RNA sequencing localized this response to G2/M-cycling cells. FOXM1 was similarly reduced following irradiation, emerged as a candidate regulator of a subset of MCPH genes, and correlated with their expression in GBM tumors. Pharmacological inhibition of FOXM1 reduced expression of selected MCPH genes and enhanced radiosensitivity in U251 cells. Together, these findings identify coordinated suppression of a FOXM1-associated MCPH program as part of the GBM radiation response, while suggesting that the radiosensitizing effects of pharmacological FOXM1 inhibition extend beyond this transcriptional axis.

cancer biology↗

bioRxiv2026

Impact of Water Deficit on Growth, Biochemical, and Physiological Traits in Eggplant MAGIC Lines

Climate change exacerbates agricultural water scarcity, necessitating the development of drought-tolerant crop varieties. This study evaluates 12 eggplant lines from a MAGIC (Multi-parent Advanced Generation Intercross) population, previously selected for contrasting responses to water deficit during the vegetative stage. To validate tolerance under adult production conditions, plants underwent five irrigation-withholding cycles over a 170-day greenhouse growing period. Yield components, the Stress Tolerance Index (STI), and physiological parameters (water status and stomatal conductance) were evaluated. Additionally, photosynthetic pigments, oxidative stress markers, antioxidant compounds, and osmolytes were quantified to characterize the biochemical basis of tolerance alongside final biomass production. The results showed that four of the five lines that were previously classified as tolerant in the vegetative stage remained among the most tolerant at the reproductive stage. Specifically, lines L13, L78 and L179 were the most productive under water-limited conditions. While L13 and L179 exhibited stable tolerance throughout all developmental stages, L78 displayed stage-specific tolerance, manifested only during the reproductive growth phase. These findings emphasise the importance of integrating early-stage screening with adult-stage validation in order to capture the full spectrum of genetic drought tolerance. The most productive lines were characterised by moderate aboveground biomass, high leaf hydration and maintained stomatal conductance. However, the strategies employed differed: while L179 exhibited high photosynthetic pigment content, L13 was characterised by high total sugar accumulation. Overall, these results provide a multi-trait roadmap and identify elite MAGIC parental lines for breeding climate-resilient eggplant cultivars.

plant biology↗