Biology subjects

Rodriguez, C.

Publications and source records attributed to Rodriguez, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Wild Luteibacter populations exhibit climate-associated divergence and distinct genomic strategies for osmotic stress tolerance

Soil bacteria play a crucial role in supporting ecosystem health, yet little is known about how wild populations adapt to abiotic stressors, like limited water availability. We used 186 Luteibacter isolates from maize roots grown in never-irrigated prairie soils collected from a steep precipitation gradient in Kansas, US to test whether climate history is associated with osmotic stress tolerance and genomic differentiation. In vitro, strains from semi-arid sites were more tolerant to osmotic-stress treatment than those from humid sites. Comparative genomics of a subset of 96 isolates identified four strongly biogeographically structured lineages and extensive accessory-genome diversity. Semi-arid climate-associated strains were enriched for genes involved in osmotic homeostasis, oxidative stress protection, motility, and type IV secretion. Humid climate-associated strains were enriched in environmental sensing, metabolic versatility, biofilm formation, iron acquisition, type VI secretion, and resource competition. GWAS identified 22 candidate genes associated with osmotic-stress tolerance, including those related to type IV pili, biofilm production, DNA repair, and phage. No candidates were shared between semi-arid and humid strains, suggesting distinct genetic mechanisms of osmotic tolerance. Predicted prophage composition was also geographically structured, although total prophage gene content did not predict osmotic-stress tolerance. Together, these results show that adaptation to long-term differences in water availability likely involves coordinated shifts in stress physiology, genome content, and ecological interactions in wild bacterial populations, providing insight into predicting microbial responses to changing climates.

microbiology↗

bioRxiv2026

In situ pulse dispersion estimation via third-harmonic generation interferometric autocorrelation for multiphoton microscopy

Three-photon microscopy enables deep-tissue imaging but is highly sensitive to excitation pulse quality, since three-photon excitation efficiency scales with the cube of instantaneous intensity. Group-delay dispersion (GDD) and third-order dispersion (TOD) accumulated through the laser and microscope optics can substantially reduce peak intensity at the focal plane, yet these quantities are rarely measured where imaging occurs. Here, we use third-harmonic generation (THG) interferometric autocorrelation, together with Dispersion Look-Up-Table Estimation (D-LUTE) and a joint two-measurement fitting procedure validated on synthetic data, to estimate baseline GDD and TOD directly at the objective focal plane, requiring only a compact autocorrelator module added to the microscope beam path. Applying this method at 1300 nm and 1600 nm excitation across two microscope systems equipped with different units of the same laser model, we find pulse durations 1.4- to 1.7-fold longer than the transform limit at every condition, driven predominantly by TOD, which varied by roughly 2.7-fold between the two systems. Using the endogenous THG signal from myelinated fibers, we further demonstrate in vivo pulse characterization in the mouse brain, finding no measurable broadening between the tissue surface and a depth of nearly a millimeter. This low-cost, easily implemented approach enables routine, in situ pulse monitoring across multiphoton microscopy platforms.

bioengineering↗

bioRxiv2026

Circulating Immune Profiling Reveals Immune Signatures Associated with Disease Stage and Outcome in Endometrial Cancer

Although the tumor immune microenvironment has been studied in endometrial cancer, the systemic immune alterations associated with disease progression and their potential prognostic significance remain poorly defined. In this study, peripheral blood immune subsets were characterized by multiparametric flow cytometry in 67 patients with EC and 20 healthy controls, including dendritic cells, MDSCs, T-cell subsets, NK cells, and exhaustion and senescence associated markers. Immune profiles were similar between healthy controls and patients with early-stage disease, whereas advanced tumors showed marked changes, including dendritic cell expansion, reduced CD4+ T-cell proportions, and increased frequencies of CD8+CD27-CD28- and CD8+CD57+ populations. Among clinicopathologic features, MDSC levels were associated with tumor grade and myometrial infiltration, while regulatory T cells were increased in TP53-mutated and microsatellite-stable tumors. In the advanced cohort (n=31), non-responders frequently displayed elevated CD8+, CD8+CD27-CD28-, and CD8+CD57+ levels alongside decreased CD27+CD28+ proportions. In multivariable Cox models, higher baseline CD8+ (HR 1.13), CD8+ CD27-CD28- (HR 1.04), and CD8+CD57+ proportions (HR 1.07; all p<0.05) were independently associated with shorter PFS, whereas higher CD27+CD28+ levels were associated with improved PFS. CD27-CD28- proportions were also linked to worse PFS by Kaplan-Meier analysis (HR 5.1, log-rank p=0.005). Longitudinal analysis (n=28) showed that senescent-like lymphocyte levels remained associated with progression across timepoints (OR 18.80), whereas total CD8+ proportions diverged progressively, reaching significance only from 6 months onward. Together, these findings identify systemic immune remodeling as a characteristic of advanced endometrial cancer and support the potential of circulating immune profiling for patient stratification and prognostic assessment, pending validation in larger prospective cohorts.

cancer biology↗

bioRxiv2026

Dual Th1 and tissue-repair Treg cells accumulate in skeletal muscle preserving tissue integrity during infection

Chronic infections require mechanisms that limit tissue damage while preserving pathogen control, yet the contribution of regulatory T (Treg) cells to this balance remains unclear. In this study, we characterized Treg cell responses during a chronic parasitic infection using experimental Trypanosoma cruzi infection as a model of persistent low-level parasitism and chronic tissue inflammation. We found that, although Treg cell numbers decline in the spleen, they accumulate in parasite-affected tissues such as skeletal muscle, where they adopt a combined Th1-associated and tissue-repair program. Systemic Treg cell depletion had limited impact on immune and disease-associated parameters, whereas local depletion in skeletal muscle exacerbated tissue damage and increased parasite burden. Moreover, transient systemic perturbation of Treg cells during the acute phase impaired their long-term accumulation in skeletal muscle, resulting in increased tissue damage and parasite burden during chronic infection. Additionally, accumulation of reparative Treg cells in skeletal muscle was impaired in the absence of ST2. Together, these findings identify a tissue-adapted Treg cell population that integrates inflammatory and reparative programs to preserve skeletal muscle integrity during chronic parasitic infection. SUMMARYChronic parasite infection drives the emergence of tissue-adapted regulatory T cells that integrate Th1-associated and tissue-repair programs. These cells accumulate in skeletal muscle, where they preserve tissue integrity while contributing to microbial control, highlighting the dynamic specialization of Treg cells across disease stages.

immunology↗

bioRxiv2026

Quantifying the mechanisms of vaccine-induced serotype replacement in Streptococcus pneumoniae using genome-informed modelling

Streptococcus pneumoniae is a colonizer of the childs nasopharynx and a leading cause of invasive pneumococcal disease (IPD). Despite widespread use of pneumococcal conjugate vaccines, recent rebounds in IPD incidence have coincided with serotype replacement. Whether this phenomenon is driven by the replacement of serotypes within lineages or the replacement of the lineages themselves is unclear. Here, we quantified the relative contribution of these two mechanisms to serotype replacement in carriage and their consequences for IPD. We combined nationwide longitudinal surveillance of carriage and IPD in children from 2002 to 2023 with whole-genome sequencing. Observed lineage-specific carriage rates across PCV-related periods were fitted with polynomial logistic regression and compared with two counterfactual scenarios, each isolating one mechanism with: (i) fixed serotype composition within varying lineages and (ii) serotype shifts within fixed lineage carriage rates over time. Carriage dynamics were consistent with an 82% contribution of serotype shifts within persistent lineages. Estimates of serotype-specific IPD incidence derived from this predominant scenario correlated with observed IPD trends. These findings quantify the dominant role of serotype replacement within persistent lineages, disentangling the vaccine-driven adaptive history of S. pneumoniae.

microbiology↗

bioRxiv2026

Smad1 and Smad5 differentially transduce BMP signaling during in vitro differentiation of mouse embryonic stem cells into dorsal interneurons

A central unresolved question in development biology is how systems of overwhelming complexity arise from relatively few families of growth factors. Compounding this issue, signaling pathways often show signal convergence, where many ligands interact with fewer receptors, which then signal through a single second messenger complex. Here we investigate this question in the context of bone morphogenetic protein (BMP) signaling and its role directing dorsal spinal cord development, focusing on two receptor-regulated (R) Smads, Smad1 and Smad5. Multiple models have been proposed for their mode of action from acting redundantly through combined signal strength, to having distinct activities that drive different fate outcomes. We sought to distinguish between these models by generating CRISPR-edited Smad1 and Smad5 null mouse embryonic stem cell (ESC) lines to dissect the cell fate of activities of individual R-Smads, with a resolution not possible in vivo. Using a directed differentiation protocol for dorsal interneurons (dI), together with bioinformatic analyses, we have defined the roles of the R-Smads at key decision points along the dI specification timeline. Together, these findings support a model in which Smad1 and Smad5 play largely distinct roles in dorsal spinal cord development. While both R-Smads can activate canonical BMP-responsive transcriptional targets, they asymmetrically contribute to cell fate specification. Smad1 plays a restricted role, while Smad5 has a dominant role, regulating dorsal progenitor transcriptional dynamics and reiteratively directing the dorsal-most dI fates.

developmental biology↗

bioRxiv2026

Improving All-Atom Molecular Dynamics Models for Quantitative Prediction of Nanopore Blockade Current

All-atom molecular dynamics has become an indispensable tool in development of nanopore sensors of biological information. In a typical nanopore experiment, measurements of ionic current flowing through a nanopore report on the chemical structure of biomolecules that pass through the nanopore. Such experiments alone are often insufficient to relate the structure of the biomolecules to the ionic current modulations. The molecular dynamics method can establish such a relationship directly through a brute force simulation under applied electric field. Here, we examine the ability of molecular dynamics force fields to reproduce experimentally measured nanopore blockade currents produced by single-stranded DNA. Our simulations show that none of the "off the shelf" force fields (CHARMM36, AMBER Parmbsc1 and DES-AMBER) is capable of reproducing experimental data with the desired level of accuracy. To improve the accuracy, we examined and refined interactions between ions, protein nanopores and DNA, guided by experiments designed specifically for this purpose. Ultimately, the introduction of surgical corrections to non-bonded interactions within the CHARMM36 force field produced a favorable agreement between simulation and experiment. This refined parameterization, initially developed for nanopore sensing simulations, may have broader applications in computational studies of DNA-protein systems.

biophysics↗

bioRxiv2026

A family of small proteins links c-di-GMP riboswitch signaling with sporulation in Clostridioides difficile

Cyclic diguanosine monophosphate (c-di-GMP) is a ubiquitous bacterial second messenger that coordinates lifestyle transitions, virulence, and developmental processes. In Clostridioides difficile, elevated c-di-GMP levels inhibit sporulation, but the underlying mechanism remained unclear. Here, we identified a conserved family of small, membrane-associated proteins encoded by c-di-GMP riboswitch-regulated genes. Transcriptomic analyses revealed that c-di-GMP represses these genes, and reporter assays demonstrated riboswitch-dependent transcriptional regulation via premature termination mechanism. Overexpression of a single member, CD1980.2, was sufficient to trigger the transcriptional activation of sporulation genes, including sigma factors and their regulons, and to increase spore formation. Conversely, sporulation efficiency decreased proportionally with the number of deleted small protein genes, and the strain lacking all seven genes displayed a severe sporulation defect, underscoring their cumulative and functionally redundant roles. Elevating c-di-GMP levels in the deletion mutant did not further reduce sporulation, supporting a model in which c-di-GMP inhibits spore formation by repressing the expression of this small-protein family. Our work establishes these small proteins, encoded by c-di-GMP riboswitch-regulated genes, as important mediators of developmental output in C. difficile. Their redundancy, conservation, and integration into riboswitch regulatory pathways highlight their central role in spore formation, a process essential for pathogen persistence and transmission. These findings expand the repertoire of components regulated by second-messenger signaling in bacterial physiology.

microbiology↗

bioRxiv2026

Fluorescently-labeled split-QF hemidrivers: simplifying and enhancing methods enabling intersectional targeting of discrete cell types

Single cell transcriptomics data predict greater cell type diversity than previously appreciated, defined by combinatorial gene expression "codes". These codes can enable intersectional targeting strategies for selectively labeling and manipulating predicted cell types, thereby facilitating functional tests to resolve cell-specific roles and refine cell-type definitions. One such approach cleaves driver components of binary expression systems (e.g., Gal4/UAS and QF/QUAS) into two co-dependent halves, an Activation Domain (AD) and a DNA Binding Domain (DBD). The transcriptional activity of these "split-drivers" (aka, hemidrivers) is only reconstituted in cells that co-express them. While widely used in invertebrates, these systems have yet to be systematically deployed in vertebrates. Here, we developed a series of fluorescently labeled split-QF and QF2 hemidrivers via direct reporter fusions or the 2A viral peptide co-expression system. Fluorescent labeling serves to 1) simplify hemidriver transgenic line creation and maintenance, 2) allow AD and DBD intersects to be visualized directly, and 3) enable robust quality control assessments of on-target efficacy and off-target activity. These resources can enhance transgenic targeting specificity, enabling functional dissections of cell types revealed by single cell transcriptomics. SUMMARYWe engineered fluorescently labeled split-QF and -QF2 hemidrivers in zebrafish to simplify intersectional targeting tool generation and enable robust quality control assessments of split-driver function.

genetics↗

bioRxiv2026

Performance of shotgun metagenomic sequencing for detection of fungi and parasites across clinical sample types: a multicenter retrospective study.

To evaluate the diagnostic performance of clinical shotgun metagenomic sequencing (SMg) for detecting medically relevant fungi and parasites compared with standard of care (SoC), and to define read-based thresholds for interpretation, we retrospectively analyzed 198 clinical samples from 187 patients across four university hospitals (2018-2022): blood (n=37), faeces (n=63), respiratory fluids (n=54), other biological fluids (n=24), and tissue biopsies (n=20). Total nucleic acids were sequenced ([≥]10 million reads per library) and processed with MetaMIC v2.2.1. Data were normalized as reads per million (RPM). Receiver operating characteristic analyses were used to derive optimal RPM thresholds by sample type. SoC identified microorganisms in 152/198 samples (76.8%). All 46 SoC-negative samples were also negative by SMg. At the genus level, SoC identified 187 taxa and SMg 175. Of these, 147 (78.6%) were detected by both methods, 40 (21.4%) by SoC only, and 28 (14.9%) by SMg only. The overall genus-level F1-score was 0.84. Quantification cycle (Cq) values (n=57) correlated inversely with RPM (p<0.001), and no false negatives occurred with Cq<28.6. Optimal thresholds were 0.06 RPM for faeces (AUC 0.89), 0.07 for respiratory fluids (AUC 0.93; sensitivity 88.9%, specificity 90.7%), 0.09 for blood (AUC 0.99), 0.19 for other fluids (AUC 0.94), and 0.57 for biopsies (AUC 0.89). A global threshold of 0.06 RPM yielded an AUC of 0.92 (sensitivity 88.9%, specificity 88.5%). A pragmatic uniform 0.1 RPM threshold maintained performance, while sample-type specific thresholds further improved accuracy, supporting standardized implementation of clinical metagenomics for fungal and parasitic diagnostics.

microbiology↗

bioRxiv2026

Behavioral, hormonal, and chemical responses to seasonality in poison frogs with divergent reproductive strategies

Seasonal rainfall shapes biological responses in tropical ecosystems, yet how tropical organisms integrate behavioral and physiological responses to cope with seasonality remains poorly understood. We assessed how four poison frog species with contrasting reproductive strategies respond to dry and wet season environmental conditions. We quantified spatial behavior, microhabitat use, hormone release rates, and chemical defenses in two seasonal breeders (Allobates femoralis and Ameerega trivittata) and two year-round breeders (Ameerega macero and Ameerega shihuemoy). Seasonal breeders exhibited pronounced sex-specific shifts in space use, where males expanded their space use during the wet season, likely to track reproductive opportunities, while A. femoralis females increased their spatial use during the dry season, likely responding to foraging demands when prey resources are sparse. Year-round breeders maintained similar space use across seasons, likely reflecting their ability to access key resources within the same space to reproduce year-round. Microhabitat use was flexible, as seasonal breeders shifted toward humid refugia during the dry season and reproduction-associated microhabitats during the wet season, whereas year-round breeders selected microhabitats that facilitate continuous reproduction across seasons. Despite these behavioral responses, water-borne corticosterone and testosterone, as well as chemical defenses, showed no consistent seasonal variation, suggesting that behavioral responses may be partially decoupled from shifts in endocrine and chemical defenses. These results support a role for behavioral buffering in mediating responses to seasonal environmental variation. However, given the increasing unpredictability in rainfall timing and intensity as a result of climate change, how these coping strategies will function in the long term is uncertain.

animal behavior and cognition↗

bioRxiv2026

Therapeutic scheduling of WEE1 inhibition preserves T cell function and promotes immune control of HPV⁺ tumors

Human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV OPC) is driven by viral E6 and E7 oncoproteins, which disrupt G1 checkpoint control and impose selective dependency on WEE1-mediated G2/M regulation. While this vulnerability confers sensitivity to WEE1 inhibition, its immunologic consequences remain poorly defined, and the challenge of eliciting antitumor immunity without compromising immune fitness has limited clinical translation. Here, we show that WEE1 inhibition elicits durable antitumor immunity in immunocompetent models of HPV OPC. Using murine and human preclinical systems, we demonstrate that the WEE1 inhibitor azenosertib (ZN-c3) mediates tumor control through both cell-autonomous cytotoxicity and immune-dependent mechanisms requiring T cells and conventional dendritic cells. Mechanistically, HPV tumor cells are deficient in STING signaling and fail to mount canonical type I interferon responses. Instead, tumor cell-intrinsic cGAS drives immune activation through STING-competent host cells within the tumor microenvironment, revealing a non-cell-autonomous relay that circumvents viral immune evasion. Intermittent WEE1 inhibition preserves T cell fitness while maintaining antitumor efficacy, and mice achieving complete responses develop immunologic memory capable of rejecting tumor rechallenge. These findings establish intermittent WEE1 inhibition as an immune-permissive therapeutic strategy that enables antigen-specific T cell responses in HPV-driven malignancies and provides a mechanistic rationale for combination with immunotherapy.

cancer biology↗

bioRxiv2025

In vivo human embryonic spinal cord atlas validates stem cell-derived human dorsal interneurons and reveals ASD spinal signatures

Restoring somatosensory function after spinal cord injury (SCI) faces fundamental challenges: neuronal subtypes must match both axial position and circuit identity, yet the developmental patterning of human dorsal spinal interneurons (dIs) remains incompletely defined. Here, we integrate six single-cell transcriptomics datasets derived from human embryonic spinal cord tissue spanning gestational weeks 4-25 to generate a reference atlas of early human somatosensory circuit development. The atlas reveals molecular signatures underlying expansion and specialization of dI4 and dI5 interneuron populations associated with mechanosensory and nociceptive processing. Guided by this resource, we established a neuromesodermal progenitor-based differentiation approach that generates dorsal interneurons spanning anterior-posterior identities. Comparison of in vivo and in vitro dI4/dI5 subclasses identified conserved gene networks associated with sensory modalities and revealed enrichment of autism spectrum disorder-associated genes within mechanosensory interneuron populations. Together, these findings clarify how human dorsal spinal interneuron diversity is established.

neuroscience↗

bioRxiv2025

Subtype-Specific Dependencies and Drug Vulnerabilities Enable Precision Therapeutics in Head and Neck Cancer

Molecular heterogeneity in head and neck squamous cell carcinoma (HNSCC) is well recognized, yet existing subtype frameworks remain largely descriptive and have not translated into therapeutic decision-making. Here, we establish a mechanistic platform that converts transcriptomic diversity into drug-actionable tumor states. Integrating multi-cohort RNA-seq from 727 tumors across five independent datasets, genome-scale CRISPR dependency maps, and pharmacologic screening, we define distinct tumor survival circuits across HPV-negative HNSCC and nominate subtype-matched therapeutic strategies. These circuits encompass a proliferative axis (MYC, MET/FAK, inflammatory and translational programs), an epithelial-differentiated/adhesion program, an EMT-like state with stromal activation, and mitochondrial/oxidative metabolic states, each mapping to selective liabilities (e.g., mitotic/autophagy control, ERBB/PI3K and cadherin signaling, OXPHOS/mitochondrial translation, and G2/M-integrin-Notch pathways, respectively). We then develop a transcriptomic predictor of EGFR-inhibitor response using machine learning and validate it in prospectively collected, fresh patient-derived 3D microtumors. The resulting 13-gene signature identifies erlotinib-responsive tumors (R = 0.93) and maps biologically to an epithelial-differentiated state, outperforming EGFR expression alone. Our study establishes a subtype-to-dependency-to-therapy framework, enabling precision stratification and providing a clinically feasible path for prospective biomarker deployment.

bioinformatics↗

bioRxiv2025

Nanobodies targeting hnRNPA2/B1 and tau

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) is an RNA-binding protein that mislocalizes to the cytoplasm and forms stress-induced granules in tauopathy and multisystem proteinopathy. It also preferentially interacts with oligomeric tau and is required for tau-mediated neurodegeneration in a mouse model of Alzheimers disease. To study endogenous hnRNPA2/B1 and tau, we generated nanobodies that specifically recognize these proteins. We screened yeast surface display nanobody libraries using an avidity-enhanced screening strategy that enabled selection of binders against short peptide ligands. This led to isolation of anti-hnRNPA2/B1 and anti-tau nanobodies with defined epitopes. Directed evolution of the anti-hnRNPA2/B1 nanobody improved binding affinity by over 20-fold but caused cytoplasmic aggregation, demonstrating a tradeoff between affinity and intracellular behavior. Although the final nanobodies retained modest affinities, they showed robust intracellular colocalization with their targets. Furthermore, fusion to ubiquitin ligase adaptor domains significantly decreased hnRNPA2/B1 and tau levels. Collectively, these nanobodies provide valuable tools for studying hnRNPA2/B1 and tau dynamics in their native cellular context.

bioengineering↗

bioRxiv2025

Lower Airway Dysbiosis in NTM+ Bronchiectasis is Associated with NET-Predominant Severe Phenotypes

RationaleThe discoveries of neutrophilic inflammation and Pseudomonas-dominant pulmonary dysbiosis have helped pave the way for host-directed therapy in bronchiectasis. Substantial knowledge gaps remain about the interplay between neutrophilic signatures and microbes in non-tuberculous mycobacterial lung disease (NTM-LD), a phenotypically diverse lung infection that is increasingly prevalent in the United States and other parts of the world. ObjectivesEvaluate the lower airway microbiota and neutrophilic traits in NTM- and NTM+ bronchiectasis. Methods16S rRNA gene sequencing, cell counts and neutrophil extracellular trap (NET) immunoassays were performed on bronchoscopic lower airway samples in 200 bronchiectasis subjects (108 NTM-, 92 NTM+). A preclinical model of oral commensal micro-aspiration and NTM infection was used to profile the murine lower airways with flow cytometry and a NET assay. Measurements and Main ResultsLower airways of NTM+ bronchiectasis patients were enriched with Mycobacterium and oral commensals (e.g., Veillonella, Prevotella). NET levels were higher in NTM+ BAL. Mycobacterium and oral commensals co-occurred with NET and neutrophils in network studies. Distinct oral commensal taxa associated with severe disease phenotypes such as cavitary disease and exacerbators. In a murine micro-aspiration model, the combination of oral commensals and Mycobacterium led to a sustained pro-inflammatory immune response marked by an increase in Th17, {gamma}8T cells, PD-1+ T lymphocytes as well as higher NET levels. ConclusionsOur analyses showed that distinct microbiome features beyond the primary pathogen can contribute to neutrophilic inflammation and severe disease phenotypes in bronchiectasis/ NTM-LD.

immunology↗

bioRxiv2025

Expression of vimentin intermediate filaments in epithelial cells promotes cell migration and cell matrix interaction in 3D

During a variety of physiological and pathological processes, such as development, wound healing, and tumor progression, epithelial cells collectively invade into their surroundings. Vimentin intermediate filaments (VIFs) are often observed to play a role in the epithelial cells located at the margins of 2D cultures. However, their role in 3D collective cell behavior remains underexplored. Here, we investigate how induced vimentin expression affects 3D multicellular architecture and mechanics in luminal breast cancer cells (MCF-7) that ordinarily express keratin intermediate filaments only. We find that vimentin expression significantly alters 3D cell cluster morphology, inducing protrusions and increasing boundary fluctuations. Furthermore, cells in vimentin-expressing clusters show enhanced, more stochastic migration. In addition, these clusters exert stronger and localized traction forces on the surrounding matrix, indicating increased cell-matrix interactions. Transcriptomic analysis corroborates these biophysical findings, revealing upregulated gene expression for cell migration and matrix adhesion, and downregulated cell-cell adhesion genes. Our results demonstrate that VIFs are critical in modulating 3D multicellular collective morphology and dynamics, promoting invasive-like behavior by enhancing cell migration and cell-matrix interactions. These results provide fundamental insights into understanding tissue morphogenesis and disease progression.

biophysics↗

bioRxiv2025

Social observation influences the trajectory of performance monitoring across trials: evidence from single-trial estimates of the ERN and CRN

The error-related negativity (ERN) and correct-related negativity (CRN) are event-related potentials (ERPs) that reflect performance monitoring following error and correct responses, respectively. Prior work demonstrates the ERN is sensitive to the motivational significance of errors, which increases under social observation. However, most studies testing how social observation impacts performance monitoring rely on trial-averaged ERPs, potentially obscuring meaningful fluctuations in ERN/CRN over time. Here, we had participants complete a Flanker task twice (social observation vs. alone) and employed mixed-effects modeling of single-trial ERPs to test if social observation impacts ERN/CRN trajectories over short (within blocks) or long (between blocks) timescales. We found that social observation selectively influenced ERN/CRN trajectories over short timescales: for blocks performed under social observation (but not alone), ERN magnitudes increased across trials and CRN magnitudes decreased. At longer timescales, ERN/CRN significantly decreased across all blocks, regardless of social observation and consistent with a vigilance decrement. To our knowledge, this is the first demonstration that social observation influences performance monitoring trajectories over short timescales. Results highlight the importance of analyzing ERN/CRN trajectories over relatively short timescales to fully characterize the impact of social observation on performance monitoring dynamics. These findings lay the groundwork for future investigation into whether social observation interacts with individual differences in motivation/affect to differentially impact performance monitoring dynamics.

neuroscience↗