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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.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

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

Combined Image-Based Profiling and Biochemical Analysis of GCaMP Overexpression Effects on Mammalian Cells

Protein-based fluorescent sensors are a powerful addition to the biology toolbox for their ability to be stably expressed within living organisms, tissues, cells, and subcellular compartments, with the capacity to report on the presence of specific target molecules or other analytes. At the same time, sensor components will unavoidably present opportunities for unintended interaction with endogenous cellular machinery, potentially confounding both sensor function and cell health. Interactions with host components may not be readily predictable during the sensor design process, especially when simultaneously optimizing many other sensor parameters such as fluorescence response, dynamic range, and kinetics. Characterizing effects of sensor expression on cells is currently a laborious ad hoc process; new methods to characterize the cell expression effects of sensors and their variants could dramatically improve sensor design pipelines, laying the groundwork to recognize potentially problematic expression side effects earlier in the iterative design and testing workflow. Here, we take a dual high-content imaging-based and biochemical approach to examine sensor interactions with native cell biology, focusing on the widely used GCaMP calcium sensor. We identify a morphology-based signature of the cellular effects of high sensor expression in a neuroblastoma cell line. Subsequently, we identify biochemical interactions between GCaMP and a component of the mammalian cytoskeleton and track morphological features in sensor-expressing cells that lack these structural components. Our findings present an entry point for engineering new minimally cross-reactive sensor versions given a contextual biological understanding of sensor overexpression. We anticipate that as this and related workflows are incorporated into sensor engineering pipelines, bioorthogonality can be more systematically assessed and prioritized in diverse sensor scaffolds.

cell biology↗

bioRxiv2026

Beyond Equilibrium Ensembles: Time Rescaling in Coarse-Grained Simulations across Single-Molecule and Condensate Regimes

Residue-level coarse-grained simulations provide a powerful route for modeling biomolecular condensates over length and time scales that are difficult to access with atomistic molecular dynamics. Coarse-grained models have been shown to reproduce many aspects of equilibrium phase behavior. However, it remains unclear to what extent such models can reproduce the relative timescales of molecular dynamics. Here, we examine this question for complex coacervates with markedly different dynamics, formed by the highly acidic intrinsically disordered protein prothymosin with four cationic partners: linker histone H1, protamine, polylysine, and polyarginine. Coexistence simulations using a residue-level coarse-grained model reproduce key equilibrium observables from experiments, including dense-phase concentrations, ionic-strength-dependent phase behavior, and chain dimensions in the dense and dilute phases. Dynamics are accelerated in these simulations, but a composition-specific time-rescaling factor captures the ionic-strength dependence of chain reconfiguration times within a given complex coacervate. In contrast, time rescaling is not transferable between dense and dilute phases or across condensate compositions and can depend on the chosen observable. These results show that agreement with measured equilibrium observables does not imply a universally transferable timescale for conformational dynamics in residue-level coarse-grained simulations. However, we find that the required time rescaling strongly correlates with the interaction energy of the protein chains, suggesting that the missing frictional effects arise from protein-protein interactions rather than solely from protein-solvent interactions, reminiscent of internal friction. Our findings highlight the need to combine thermodynamic validation with kinetic calibration when interpreting chain relaxation, molecular diffusion, and material properties from residue-level coarse-grained simulations of biomolecular condensates.

biophysics↗

bioRxiv2026

From Bile Acids to a Gas-Producing Microbiome Phenotype: A Novel Mechanism of Host-Microbiome Communication

Background Microbiome-derived metabolites regulate host physiology, yet bacterial gaseous metabolites remain largely overlooked. Traditionally regarded as fermentation end-products, bacterial gases may act as biologically active mediators of host-microbiome communication. We hypothesized that bile acids regulate bacterial gaseous metabolism and influence host epithelial responses. Methods A high gas-producing clinical Escherichia coli isolate from a patient with moderately severe acute pancreatitis was cultured with selected primary and secondary bile acids. Gas production was assessed by pressure measurements, GC-TCD and GC-MS. Biological activity was evaluated by indirect exposure of Caco-2 and PANC-1 epithelial cells, followed by apoptosis/necrosis assays and whole-transcriptome RNA sequencing. Results Bile acids markedly reshaped bacterial gaseous metabolism. Cholic acid and deoxycholic acid promoted intense gas production, whereas chenodeoxycholic acid almost completely abolished it. Despite minimal apoptosis and necrosis, bacterial gaseous metabolites induced extensive transcriptional remodeling. Caco-2 cells showed stronger responses than PANC-1 cells, particularly to deoxycholic acid-derived gases, involving inflammatory signaling, extracellular matrix remodeling, epithelial plasticity, stress responses, and cancer-associated genes including PTGS2, MMP1, PLAUR, NR4A2, and SERPINE1. PANC-1 cells exhibited a more restricted response involving oxidative stress, proteostasis, and autophagy-associated pathways. Conclusions Our findings indicate that bacterial gases are a previously underrecognized class of microbiome-derived signaling molecules capable of modulating host gene expression independently of direct bacterial contact. We identify a gas-producing microbiome phenotype regulated by bile acid composition, linking microbial metabolism with epithelial signaling. These findings expand the concept of host-microbiome communication and provide a framework for investigating bacterial gaseous metabolites in intestinal and pancreatic diseases.

microbiology↗

bioRxiv2026

Autonomous Homeostatic Synthetic Cells via Self-Gating DNA Nanopores

Homeostasis is a fundamental hallmark of living organisms, arising from the complex interplay between biochemical reactions and regulatory feedback systems. Reconstituting such self-regulating behaviour in minimal synthetic cells enables continuous, persistent operation of biochemical reactions for extended amount of time. In this work, we demonstrate a minimal homeostatic synthetic cell capable of autonomous flux regulation using DNA nanotechnology and bottom-up synthetic biology. Our homeostatic architecture consists of Giant Unilamellar Vesicles (GUVs) equipped with gated DNA nanopores, encapsulated in vitro transcription (IVT) machinery, and an RNA degradation system. We achieve homeostasis under varying external chemical stimuli specifically varying concentrations of rNTPs by implementing a negative feedback loop between rNTP influx and RNA production. In our system, DNA nanopores facilitate the influx of rNTPs from the external environment, driving internal transcription. Crucially, the transcription process generates RNA "blockers" designed to bind and gate the DNA nanopores, thereby attenuating further rNTP influx. Our system is dynamic as encapsulated RNases slowly degrade the RNA blockers, allowing the pores to reopen as blocker concentration goes down. We first characterise the functionality and gating efficiency of the DNA nanopores using both pre-synthesised and in situ produced DNA and RNA blockers. We then demonstrate that rNTP flux through these pores is sufficient to drive IVT within the GUVs. Finally, by integrating these modules, we demonstrate robust homeostasis: the system maintains a steady-state level of RNA production for up to 16 hours. By harnessing the controllability of negative feedback loop, we demonstrate thresholding of the homeostasis level using single-stranded regulator DNA. This work establishes a versatile framework for engineering adaptive and self-sustaining responsive nanomaterials and synthetic cell chassis.

biophysics↗

bioRxiv2026

Systemic hypoxia drives glycogen-fueled progression of lung adenocarcinoma

In advanced stages, lung adenocarcinoma obstructs airways and disrupts ventilation-perfusion relationships in the lung, causing systemic hypoxemia and enabling a feed-forward loop that accelerates malignancy. Systemic hypoxemia is also experienced due to common respiratory comorbidities such as chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), potentially accelerating malignancy. In a statewide electronic health record network, pre-existing COPD (598 matched pairs) or sleep apnea (235 matched pairs) independently predicted worse survival following incident lung cancer diagnosis. Since the mechanistic basis of the link between malignancy and hypoxia is not well understood, we created systemic hypoxia in KrasLSL-G12D/+;Trp53fl/fl (KP) mice by delivering low inspired oxygen concentrations (8% inspired oxygen; 8 h daily). Hypoxia nearly doubled tumor multiplicity and selectively remodeled cancer central carbon metabolism. Spatially resolved metabolomics revealed marked tumor-compartment glycogen accumulation, elevated tricarboxylic-acid cycle intermediates, and depleted glycolytic pools. Quantitative proteomics across cellular models and autochthonous tumors demonstrated that systemic hypoxia drives glycogen mobilization selectively through the lysosomal enzyme acid -glucosidase (GAA). Tumor-cell-autonomous deletion of GAA eliminated the hypoxia-driven growth advantage and disrupted downstream anabolic biosynthetic pathways. Thus, systemic hypoxia drives lung adenocarcinoma expansion by mobilizing lysosomal glycogen reserves through GAA to sustain proliferative growth.

cancer biology↗

bioRxiv2026

IBD-Derived Colonic Fibroblasts Exhibit an Osteopontin-Enriched Secretome, and Osteopontin Restrains Human Colonic Organoid Maturation

Background: Intestinal fibroblasts are extensively remodeled in inflammatory bowel disease (IBD), yet the soluble stromal signals that directly influence epithelial maturation remain incompletely understood. We examined whether fibroblasts derived from inflamed IBD colon display an osteopontin (OPN; SPP1)-enriched secretory phenotype and whether extracellular OPN directly modifies non-neoplastic human colonic epithelium. Methods: Conditioned media from 5 noninflamed-associated fibroblast (NAF) and 4 inflammatory-associated fibroblast (IAF) cultures were analyzed in the validated multi-donor cytokine-array matrix, with orthogonal SPP1 RT-qPCR validation in a complementary fibroblast cohort. Recombinant OPN was then tested in human colonic organoids from 3 donors using donor-resolved molecular and functional analyses under standard, fibroblast-conditioned, and WNT-modified culture conditions. Donor identity defined biological replication. Results: OPN showed the strongest positive rank-based separation between IAF and NAF cultures: all 4 IAF values were higher than all 5 NAF values (Cliff's delta=1.00; exact Mann-Whitney P=0.0159; median ratio=3.64; Benjamini-Hochberg q=.19). Fibroblast RT-qPCR showed approximately 10-fold higher mean SPP1 expression in IAF than NAF cultures (P<.05). In organoids, OPN consistently reduced KRT20, FABP1, CA2, and MUC2 from Day 5 to Day 9. SOX9, HES1, and NOTCH1 increased at Day 9, whereas LGR5 and ALDH provided no evidence of canonical stem-cell expansion. Organoid-area and EdU responses were modest and donor dependent. Conclusions: IBD-derived colonic fibroblasts can display an OPN-enriched secretory phenotype. In human colonic organoids, OPN is sufficient to impair epithelial maturation, whereas its effects on growth and proliferation are variable and depend on the surrounding niche.

physiology↗

bioRxiv2026

From Public Archive to Reusable Resource: Characterizing Gut Microbiome Metadata in the NCBI SRA

Public sequencing repositories contain large amounts of gut microbiome data that could support cross-study comparison, reproducibility analysis, and microbiome foundation model development. However, the extent to which these data are structured, harmonized, and reusable at archive scale remains unclear. Here, we characterized publicly available gut microbiome sequencing metadata from the NCBI Sequence Read Archive using Google BigQuery, focusing on human gut metagenome, mouse gut metagenome, and broadly annotated gut metagenome records. We evaluated temporal growth, sequencing depth, BioSample and BioProject structure, platform and instrument use, metadata completeness, host attribution, publication linkage, and research themes from linked literature. Public gut microbiome data increased substantially over time and were dominated by human-associated datasets and Illumina sequencing platforms. Core technical metadata fields were highly complete, but biological context needed for reuse, including host identity, phenotype, study design, and disease status, was often inconsistently encoded or required recovery from BioSample attributes and linked publications. In the generic "gut metagenome" cohort, host identity could be assigned for only 13.00% of BioSamples, highlighting the limitations of broad organism annotations for automated cohort construction. Publication linkage was also incomplete at the archive level, although usable text was recovered for most linked publications. Topic modeling of SRA-linked literature showed persistent emphasis on core gut microbiota composition and increasing representation of human cohort and infant microbiome studies. Overall, these findings show that public gut microbiome data are extensive and technically rich but not uniformly analysis ready. Improved metadata harmonization, publication linkage, and biological context recovery will be necessary to support reliable large-scale reuse and AI-ready microbiome data resources.

bioinformatics↗

bioRxiv2026

Resolving Heterogeneous Mechanical Domains via Physics-Aware Deep Clustering of Single-Molecule Force Spectroscopy Data

Many biological processes rely on mechanical forces, with protein molecules acting as key mediators. Understanding how proteins respond to mechanical stress is essential for conditions including cardiomyopathy and muscular dystrophy. Natural proteins such as dystrophin and utrophin are composed of heterogeneous folding domains with distinct mechanical properties; deciphering domain-level behavior provides insights into disease mechanisms and informs therapeutic strategies. Single-molecule force spectroscopy (SMFS) enables probing the mechanical properties of entire proteins, yet current approaches struggle to identify heterogeneous folding domains, particularly without prior knowledge. Here, we present the first automated framework to identify heterogeneous folding domains in SMFS data, applying both existing clustering methods and a novel physics-aware deep clustering architecture, LatentUnfold. LatentUnfold learns complementary latent representations from force magnitude and the force-extension physical relationship through dual autoencoders, jointly optimized for clustering assignments. We apply our framework to experimental SMFS data collected from a synthetic two-domain protein (ddFLN4-Titin I27) as well as natural protein constructs of dystrophin and utrophin, with Monte Carlo simulated datasets serving as controlled validation. For the synthetic protein, we recover mechanical properties consistent with previously reported values for each domain. For the natural proteins, we uncover two mechanically distinct domain populations - corresponding to the N-terminal domain and spectrin-like repeats - with differences in both unfolding force and contour length increase, and reveal different unfolding order between them for the first time. This work enables domain-level biological inference, overcoming prior limitations that relied on averaging and overlooked heterogeneity, thus advancing the understanding of mechanical behavior in protein unfolding.

biophysics↗

bioRxiv2026

High-Throughput, automated assay for detection of colonization by Candida auris

Candida auris is an emerging multidrug-resistant fungal pathogen associated with healthcare-associated outbreaks, persistent colonization, and invasive infections. Increasing demand for surveillance has created a need for high-throughput methods capable of supporting large-scale screening programs. We developed and validated an automated laboratory-developed real-time PCR assay for detection of C. auris colonization on the Hologic Panther Fusion(R) open-access platform and compared its performance with the existing BD MAX assay. Analytical performance was evaluated by assessing limit of detection, accuracy, precision, specificity, inclusivity, reproducibility, and reagent and specimen stability. The Panther Fusion(R) assay demonstrated a limit of detection of approximately 18 CFU/reaction and showed 97% overall agreement with the BD MAX assay. Positive and negative percent agreement were 94% and 100%, respectively, with excellent agreement between methods ({kappa} = 0.94). No cross-reactivity was observed with non-C. auris organisms, all five major C. auris clades were detected, and assay performance remained stable across operators, reagent and specimen storage conditions. Following implementation, 26,838 clinical specimens were tested on the Panther Fusion(R) platform. Retrospective analysis demonstrated lower equivocal (0.28%) and indeterminate (0.09%) rates than those observed on the ABI and BD MAX platforms. Among PCR-positive specimens that underwent culture, the Panther Fusion(R) assay demonstrated 87.24% culture agreement. Because retrospective data were collected during different testing periods and patient populations, comparisons between platforms were not used to assess relative assay sensitivity or specificity. Implementation of the Panther Fusion(R) assay increased surveillance testing capacity from approximately 88 to 500 specimens per shift while maintaining robust analytical performance.

microbiology↗

bioRxiv2026

Distinct roles for partially redundant transcription factors in Caenorhabditis elegans mesoderm lineage development

Developmental transcription factors often have overlapping functions, making it difficult to define the distinct roles of individual factors during lineage specification. We investigated the partially redundant transcription factors TBX-35 and CEH-51 in the Caenorhabditis elegans embryonic MS mesodermal lineage using 4D lineage tracing, reporter imaging, genetics, and single-cell RNA sequencing. In tbx-35 mutants, MS descendants showed progressively slower cell cycles and a division pattern that increasingly resembled the cousin C lineage. Fate-regulator expression also shifted toward C-like features, including ectopic pal-1 and expanded HLH-1 expression, although mutant cells did not simply adopt normal C-lineage positions. Loss of tbx-35 also impaired a later MS-dependent Notch induction in the AB lineage while leaving an earlier induction intact. CEH-51 showed a different pattern of activity whereby its protein became enriched in anterior MS daughters, and ceh-51 mutants produced later, more restricted lineage defects that were strongest in descendants of cells with higher CEH-51 levels. Single-cell profiling identified overlapping but nonidentical sets of genes dependent on the two factors. TBX-35-dependent changes were strongest at earlier stages, whereas CEH-51-dependent genes became more prominent later and were enriched in anterior MS sublineages. Finally, temperature-shift experiments determined that the severity and onset of tbx-35 mutant phenotypes depend on the maternal temperature environment and cannot be explained by differences in residual CEH-51 expression. These findings reveal that TBX-35 and CEH-51 contribute differently across the MS lineage and that reliable mesoderm development is supported by overlapping zygotic and maternal regulatory inputs.

developmental biology↗

bioRxiv2026

Bravais Lattice Sampling: Geometry-Guided Sparse Probing for Connected-Component Detection in 3D Discretized Spaces

We introduce Bravais Lattice Sampling (BLS), a two-phase method for detecting connected high-density regions in three-dimensional space. BLS places probe sites on a Bravais lattice scaled to the expected nearest-neighbour distance dNN of the target structures, then recovers cluster boundaries by depth-first expansion seeded only from occupied probes, replacing the exhaustive raster scan that conventional connected-component labelling uses to discover seeds. The spacing between probe sites is set from the covering radius of the lattice, which is what allows the method to state in advance the size below which a cluster may escape detection. The second phase, an expansion refinement activated only on probes that return an occupied voxel, verifies every edge, so the components returned are true connected components. BLS versatility allows for selection of different Bravais lattice unit cells to match the target structure; for amorphous, non-crystalline shapes, BLS can default to a simple face-centred cubic unit cell, where the expected minimum cluster size is the only parameter that needs to be set. The current BLS implementation has been developed as a post-processing tool for molecular dynamics trajectories, and was tested for searching water ice clusters of different morphologies. BLS returns component counts and maximum cluster sizes identical to exhaustive-labeller algorithms, with 100% recall; it runs at about 0.94 times the cost of depth-first search, and at 0.84 to 0.90 times the cost of the fastest other labeller in our benchmark set. This algorithm, although implemented by us for molecular dynamics applications, could be of interest in other domain areas where searching for high-density elements in 3D space is relevant.

bioinformatics↗

bioRxiv2026

CD36 phosphorylation alters the thrombospondin binding site and reduces internal cavity accessibility and volume

The cluster of differentiation 36 (CD36) is a membrane protein with broad physiological roles in health and disease, and its function is regulated in part by phosphorylation. Experimental evidence shows that phosphorylation of Thr92 reduces CD36 affinity for thrombospondin-1 (TSP-1), binding of which initiates antiangiogenic signaling, whereas phosphorylation of Ser237 decreases CD36-mediated fatty acid uptake, with implications for energy metabolism. However, the only available crystal structure of CD36 lacks phosphorylation, and the molecular mechanisms by which phosphorylation regulates CD36 function remain largely unknown. This study provides an atomically detailed computational characterization of CD36 in unphosphorylated and dual phosphorylated states, using molecular dynamics simulations with a total sampling time of 30 microseconds in combination with Markov state models. We present, to our knowledge, the first evidence of a cryptic pocket on CD36 surface that is formed by phosphorylation. This cryptic surface pocket and a loop spanning residues 121-131 form a high affinity binding site for TSP-1 derived ligands, shifting their binding away from the canonical site. We propose that this altered binding provides a molecular basis for the disruption of antiangiogenic signaling upon CD36 phosphorylation. Additionally, our data indicate that, phosphorylation increases helicity and compaction within the helix-loop region spanning residues 296-331, narrowing one of the entrances to the internal cavity and reducing its overall volume. These conformational changes provide a potential mechanistic explanation for the decrease in fatty acid uptake upon CD36 phosphorylation. Our findings provide structural insights that may inform the future design of CD36 modulators and emphasize the importance of targeting phosphorylation induced CD36 conformations in angiogenic and metabolic diseases.

biophysics↗

bioRxiv2026

Herpes simplex virus 1 subverts the mitochondrial network to support the infection: A lesson on mitochondrial versatility

Herpes simplex virus 1 (HSV-1) infects approximately 67% of the population worldwide. It establishes lifelong reservoirs in sensory neurons and has been linked to several diseases including neuronal dysfunction. Disruption of mitochondrial homeostasis is a hallmark of HSV-1 infection, however a molecular understanding of these changes and their significance is not yet well defined. HSV-1 infection causes a UL12.5-dependent inhibition of mitochondrial biogenesis through the loss of mitochondrial DNA and mitochondrial transcription factors, PGC-1 (peroxisome proliferator-activated receptor-gamma co-activator) and TFAM (mitochondrial transcription factor). Conversely, UL12.5-independent mechanisms inhibit mitochondrial fusion by activating the OMA1 metallopeptidase that cleaves the inner mitochondrial membrane fusion protein OPA1 (optic atrophy protein 1) and by down-modulating the outer mitochondrial membrane fusion protein MFN2 (mitofusin 2). This inhibition of fusion results in a smaller mitochondrial network that clusters to perinuclear regions, likely supplying energy for viral replication and envelopment. The inner mitochondrial membrane protein TIM23 is also down-modulated during infection in a UL12.5-independent mechanism. Failure of the virus to promote these changes negatively impacts the infection. Despite these changes, mitochondria are protected from mitophagy due to the viral-induced degradation of several mitophagy adaptor proteins, whereby damaged mitochondrial components, including mitochondrial DNA, are extruded via extracellular vesicles. These mitochondrial changes still support functions necessary for HSV-1 infection. Basal cell respiration is preserved, while spare respiratory capacity and extracellular acidification rates increase, indicating glycolytic activity. Mitochondrial membrane potential is also preserved. Overall, our studies provide mechanistic insight into how HSV-1 impacts mitochondria, which could contribute to viral pathogenesis.

microbiology↗

bioRxiv2026

Sport expertise and motor imagery abilities shape sensorimotor rhythm modulations during visualisation tasks: Implications for neurofeedback-based cognitive training in athletes

Kinaesthetic motor imagery (kMI) is widely used in sport to enhance motor performance by engaging cortical sensorimotor networks. Neurofeedback may further support kMI, but the optimal neural target to reinforce remains unclear. Maximal sensorimotor event-related desynchronisation (SMR-ERD) represents a relevant target as it may index sensorimotor cortex engagement, yet sport expertise has been associated with reduced SMR-ERD, potentially reflecting neural efficiency. The optimal neurofeedback target may therefore depend on sport expertise, movement expertise, and individual kMI ability. This study examined how these factors influence sensorimotor activity during kMI. We compared 17 basketball players (Experts) and 16 individuals without formal basketball training (Novices). kMI ability and frequency of use were assessed using questionnaires, while SMR-ERD was quantified using electroencephalography (EEG) during kMI. Participants imagined either a basketball-specific movement (Free throw), for which only Experts had extensive experience, or a generic movement (Box lifting), familiar to both groups. Experts reported greater kMI ability and more frequent kMI use than Novices. Only Experts exhibited significant and sustained SMR-ERD during kMI. Moreover, SMR-ERD was stronger in Experts than Novices specifically during Free throw kMI, corresponding to their movement of expertise. Nonetheless, within the Expert group, higher kMI ability was associated with reduced SMR-ERD. These findings suggest that sport expertise initially enhances voluntary recruitment of sensorimotor networks during kMI, whereas greater kMI ability may subsequently promote neural efficiency, resulting in reduced overall sensorimotor cortical activation. These results highlight the need to tailor kMI-based neurofeedback training to users' sport expertise and kMI ability levels.

neuroscience↗

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

DNA Sequence-Programmed Protein Coronas Determine Intracellular Fate and Proteostatic Stress of Carbon Nanotubes

Single-walled carbon nanotubes (SWCNTs) show promise for optical biosensing, imaging, and drug delivery, but turning them into safe, precision nanomedicine tools requires understanding how nanotube surface chemistry dictates recognition and processing by cells. Like other nanomaterials, carbon nanotubes acquire a biomolecular corona on contact with biological fluids, and corona identity is increasingly recognized as central to sensor performance and drug delivery efficacy. However, whether corona identity also governs the intracellular fate of carbon nanotubes remains largely unknown. Here, we show that the single-stranded DNA wrapping of (6,5)-enriched single-walled carbon nanotubes reprograms their protein corona, intracellular trafficking, and macrophage response. By profiling (AT)15, (GT)15, and (CT)15 wrapped SWCNTs, we show that the wrapping sequence programs both the protein corona and the resulting proteostatic stress on macrophages. Photoluminescence imaging and confocal Raman measurements reported that (AT)15 is internalized the most yet leaves the proteome and nanotube structure largely undisturbed, whereas (CT)15, taken up the least, undergoes the most aggressive intracellular degradation and drives the highest oxidative and proteostatic stress. Corona proteomics indicated that all three tested nanotubes form coronas with distinct functional identities that are responsible for divergent intracellular routes. Time-resolved intracellular proteomics combined with functional assays resolved how the host cell reorganizes its biomolecular complexity over time, including oxidative outputs, aside from a sequence-independent core response involving particle engagement, phagosomal sorting, and lysosomal processing. These findings provide mechanistic insight into nanomaterial-cell interactions and the wrapping sequence as a tunable, nucleotide-level design handle for controlling the intracellular fate of carbon nanomaterials, with potential implications for safe and effective nanomedicine platforms.

bioengineering↗

bioRxiv2026

Linoleic Acid-Lyso PG Axis promoting lipid droplet-mitochondria tethering by stabilizing Noncanonically Mitochondrial PPAR β/δ to Ameliorate Microglial Dysfunction in subarachnoid hemorrhage

Background Microglial lipid handling and mitochondrial failure contribute to brain injury after subarachnoid hemorrhage (SAH), but the lipid signals coupling these processes remain unclear. We investigated whether linoleic acid (LA) restores microglial homeostasis through lysophosphatidylglycerol 16:0 (LPG[16:0]) and peroxisome proliferator-activated receptor-{delta} (PPAR{delta}). Methods Cerebrospinal fluid metabolomics included 30 patients with aneurysmal SAH and 10 control participants. Mechanisms were examined in a blood-injection mouse model and hemoglobin-exposed primary mouse microglia using targeted lipidomics, RNA sequencing, mitochondrial and phagocytosis assays, pharmacological perturbation, fractionation, coimmunoprecipitation, thermal shift analysis, and structural modeling. Behavioral outcomes were evaluated by open-field, Y-maze, and Morris water-maze testing. Results; CSF LA was higher in SAH and discriminated the groups within this cohort (area under the curve, 0.9967 [95% CI, 0.9859-1.000]; P<0.001). LA attenuated inflammatory activation and restored phagocytosis, mitochondrial membrane potential, respiration, and ATP production in hemoglobin-exposed microglia. LA restored PLA2G15-associated LPG(16:0), which phenocopied these effects. Transcriptomic and inhibitor analyses identified PPAR{delta} as a downstream effector. LPG(16:0) increased PPAR{delta} stability, and fractionation and protease protection identified a PPAR{delta} pool on the cytosolic face of the outer mitochondrial membrane. PPAR{delta} associated with PLIN2 and CPT1A, promoted lipid droplet-mitochondria apposition, and supported fatty acid oxidation. In mice, LA reduced neuroinflammatory injury and partially improved anxiety-related behavior and spatial memory.

neuroscience↗