Biology subjects

Brown, J. D.

Publications and source records attributed to Brown, J. D..

6 recordsLinked to original sources

bioRxiv2026

Perceiving latent dynamics: Innate and coachable visual estimation of limb damping

Humans are remarkably adept at extracting latent dynamic information from purely visual cues. Prior work shows that people can innately estimate differences in limb stiffness using solely their visual observation of movement, which suggests that components of mechanical impedance may be embedded within humans internal predictive models of movement. We tested whether humans can similarly perceive damping, a force-velocity relationship, and whether targeted coaching can enhance this visual ability. Specifically, 30 participants observed abstract two-link arm simulations with systematically varied elbow damping and rated their perceived level of damping for several trials. Participants completed two sessions separated by one of three brief coaching interventions: (1) no coaching, (2) coaching to attend to hand velocity, or (3) coaching to attend to elbow-angle velocity. Results reveal that (1) humans can innately perceive changes in arm damping using solely their visual observation of motion and (2) coaching further improved performance, with the elbow-angle coaching group showing a significantly greater increase in rating accuracy compared to the other two groups. This work extends our understanding of how action-perception coupling supports inference of mechanical impedance. Moreover, we demonstrated that perceptual strategies for estimating damping are malleable and can be systematically improved through coaching. We not only identified the visual cues observers relied on but also guided them toward more classifiable features, effectively strengthening their perceptual models of limb dynamics. Author summaryHumans are remarkably adept at understanding an objects latent dynamic properties simply by watching it move, even when the underlying forces are unseen. In this paper, we demonstrated that people can notice differences in how "damped" a moving limb is using vision alone. Moreover, we found that brief coaching helped participants focus on the most informative features, significantly improving their ability to differentiate the damping levels. These results demonstrate how people can visually infer aspects of movement that are normally thought to require physical interaction, offering insight into how the motor system links action and perception. They also show that strategies can be shaped and improved, supporting real-world healthcare applications. In stroke rehabilitation, physical therapists physically assess the resistance of a patients limb, so better guidance on the most relevant visual cues can help clinicians learn faster and even provide care remotely. In robot-assisted surgery, surgeons operate a console to perform procedures with limited or no force feedback, so they must estimate tissue dynamics properties largely from visual observation. Understanding how people visually estimate these dynamics can inform training for more precise surgical decisions. Overall, our findings clarify how humans interpret movement dynamics and how coaching can support more consistent and accurate perceptual decisions.

neuroscience↗

bioRxiv2025

Moisture and material shape microbial communities in the built environment through disturbance-productivity relationships

The built environment houses diverse microbial communities whose diversity and composition differ among building materials and environmental conditions. Ecological theory makes predictions about how productivity and diversity shape communities, and experiments in the built environment provide an opportunity to test these. We manipulated moisture (constant or repeated wet-dry cycling) on three common building materials to test predictions about alpha and beta diversity. The most productive material (oriented strand board) supported the highest bacterial alpha and beta diversity, and these diversity levels were reduced by repeated drying disturbances. Diversity patterns for fungi were more variable, with the highest alpha diversity on low-moderate productivity material (gypsum wallboard). Fungal beta diversity was reduced by disturbance on high-productivity material, but increased on the other materials. These patterns were driven largely by members of Bacillaceae, Sphingomonadaceae, and Aspergillaceae that reached high abundances in some treatments. Differences between bacteria and fungi may be due to the scale-dependence of productivity-diversity relationships. Together, these results indicate that disturbances can interact with building materials, in some cases leading to variation in community composition that makes it difficult to predict the conditions under which microorganisms with potential importance to health and safety will occur. ImportanceThe built environment--the homes, workplaces, vehicles, and other spaces where people spend most of their time--contains an enormous diversity of microorganisms with significance for human wellbeing, yet we know little about the factors shaping these microbial communities. We found that patterns of wetting and drying that mimic indoor leaks on common building materials affects the diversity of bacteria and fungi growing on the materials. But the identity of these microorganisms differed from one building material to another, and this was especially variable with wetting and drying. This means that common disturbances that lead to microbial growth in homes and offices can make it difficult to predict which microbes, including those that represent health threats to people, will occur in the built environment.

microbiology↗

bioRxiv2025

Wnt5a-mediated Adipo-Cardiac Interorgan Communication in HFpEF

BackgroundObesity is an important risk factor in heart failure with preserved ejection fraction (HFpEF), but the precise mechanisms that drive obesity-associated cardiac remodeling are not well understood. Our previous work has shown that increased expression of the natriuretic peptide clearance receptor (Nprc) may drive cardiac remodeling in response to high fat diet. In this study, we hypothesized that Nprc plays a central role in preventing and reversing experimental HFpEF. MethodsNprc knockout mice were generated to induce global, cardiomyocyte-specific, or adipocyte-specific disruption of the Nprc (Npr3) gene. HFpEF was induced by the 2-hit stress of L-NAME and high fat diet. Outcomes measured included echocardiography, exercise endurance, invasive catheterization, and histologic assessment. Differential gene expression in adipocyte Nprc knockout visceral adipose tissue was investigated via bulk RNA sequencing and validated by RT-qPCR and culture of H9C2 cells with or without Wnt5a treatment. Adipocyte-mediated Wnt ligand release was interrupted in vivo via LGK974 injection in mice subjected to HFpEF conditions. ResultsGlobal inducible Nprc knockout prevented and reversed structural, hemodynamic, echocardiographic, and exercise tolerance features of HFpEF. This effect was found to be driven by adipocyte-specific, not cardiomyocyte-specific Nprc expression. Bulk RNA sequencing of adipocyte-specific Nprc knockout in peri-gonadal visceral adipose tissue identified downregulation of several secretory pathways, including Wnt pathways. Wnt5a was identified as one of the most downregulated genes by RNA sequencing and specifically validated by qPCR. Wnt5a exposure increased cardiomyocyte hypertrophy in vitro, and LGK974 (PORCN inhibitor) treatment in vivo decreased circulating Wnt5a levels and improved cardiac remodeling in HFpEF. ConclusionsOur study identifies a novel crosstalk mechanism between cardiomyocytes and adipocytes in obesity-associated HFpEF driven by natriuretic peptide-mediated inhibition of release of Wnt5a from adipocytes.

molecular biology↗

bioRxiv2024

The transcription factor ZNF469 regulates collagen production in liver fibrosis

Non-alcoholic fatty liver disease (NAFLD) - characterized by excess accumulation of fat in the liver - now affects one third of the worlds population. As NAFLD progresses, extracellular matrix components including collagen accumulate in the liver causing tissue fibrosis, a major determinant of disease severity and mortality. To identify transcriptional regulators of fibrosis, we computationally inferred the activity of transcription factors (TFs) relevant to fibrosis by profiling the matched transcriptomes and epigenomes of 108 human liver biopsies from a deeply-characterized cohort of patients spanning the full histopathologic spectrum of NAFLD. CRISPR-based genetic knockout of the top 100 TFs identified ZNF469 as a regulator of collagen expression in primary human hepatic stellate cells (HSCs). Gain- and loss-of-function studies established that ZNF469 regulates collagen genes and genes involved in matrix homeostasis through direct binding to gene bodies and regulatory elements. By integrating multiomic large-scale profiling of human biopsies with extensive experimental validation we demonstrate that ZNF469 is a transcriptional regulator of collagen in HSCs. Overall, these data nominate ZNF469 as a previously unrecognized determinant of NAFLD-associated liver fibrosis.

molecular biology↗

bioRxiv2020

Erythropoietin regulates transcription and YY1 dynamics in a pre-established chromatin architecture

The three dimensional architecture of the genome plays an essential role in establishing and maintaining cell identity. By contrast, the magnitude and temporal kinetics of changes in chromatin structure that arise during cell differentiation remain poorly understood. Here, we leverage a murine model of erythropoiesis to study the relationship between chromatin conformation, the epigenome, and transcription in erythroid cells. We discover that acute transcriptional responses induced by erythropoietin (EPO), the hormone necessary for erythroid differentiation, occur within an invariant chromatin topology. Within this pre-established landscape, Yin Yang 1 (YY1) occupancy dynamically redistributes to sites in proximity to EPO-regulated genes. Using HiChIP, we identify chromatin contacts mediated by H3K27ac and YY1 that are enriched for enhancer-promoter interactions of EPO-responsive genes. Taken together, these data are consistent with an emerging model that rapid, signal-dependent transcription occurs in the context of a pre-established chromatin architecture.

molecular biology↗

bioRxiv2020

BET Bromodomain Proteins Regulate Transcriptional Reprogramming in Genetic Dilated Cardiomyopathy

The bromodomain and extraterminal (BET) family of epigenetic reader proteins are key regulators of pathologic gene expression in the heart. Using mice carrying a human mutation in phospholamban (PLNR9C) that develop progressive dilated cardiomyopathy (DCM), we previously identified the activation of inflammatory gene networks as a key early driver of DCM. We reasoned that BETs control this inflammatory process, representing a key node in the progression of genetic DCM. Using a chemical genetic strategy, PLNR9C or age-matched wild type mice were treated longitudinally with the BET inhibitor JQ1 or vehicle. JQ1 abrogated DCM, reduced cardiac fibrosis, and prolonged survival in PLNR9C mice by inhibiting inflammatory gene network expression at all disease stages. Cardiac fibroblast proliferation was also substantially reduced by JQ1. Interestingly, JQ1 had profound effects on pathologic gene network expression in cardiac fibroblasts, while having little effect on transcription in cardiomyocytes. Using co-immunoprecipitation, we identified BRD4 as a direct and essential regulator of NF{kappa}B-mediated inflammatory gene transcription in cardiac fibroblasts. In this this model of chronic, heritable DCM, BETs activate inflammatory gene networks in cardiac fibroblasts via an NF{kappa}B-dependent mechanism, marking them as critical effectors of pathologic gene expression.

cell biology↗