Biology subjects

Anderson, M. D.

Publications and source records attributed to Anderson, M. D..

4 recordsLinked to original sources

bioRxiv2025

Development of the Early Childhood Duodenum across Ancestry, Geography and Environment

During early childhood, the proximal small intestinal mucosa plays a central role in growth, metabolism, immune priming, and neuronal development. Yet the cellular architecture and environmental responsiveness of the human small intestinal mucosa during this period remain poorly defined. Here, we generate a comprehensive cellular and spatial map of the duodenum from 87 children aged 6 months to 13 years, representing diverse ancestries and geographic contexts. This atlas integrates single-cell transcriptomic and spatial profiling with data on diet, social drivers of health, and environmental exposures. Using these data, we define mucosal cellular composition and chart its developmental trajectory in early childhood. Comparative analyses of children residing in the United States (US) and Pakistan reveal a differentiated enterocyte subset expressing the aquaglyceroporin, AQP10 (AQP10+ enterocyte), that is enriched in children from the US. We show that emergence of this enterocyte state depends on lipid exposure to intestinal stem cells and correlates with dietary fat intake. We also identify a previously-undescribed thyrotropin-releasing hormone (TRH+) enteroendocrine cell and provide evidence for a local endocrine-epithelial-lymphocyte circuit. Our work establishes a detailed framework for pediatric duodenal mucosal development and illuminates how intestinal cellular dynamics are shaped by age and environment.

developmental biology↗

bioRxiv2025

Behavioral and Modeling Evidence that Eye Movements Bias Self-motion Perception

To navigate the world, humans must integrate what they see with how they move. As the body moves, for example, the eyes rotate to explore the environment; these eye rotations, in turn, alter the visual signals used to judge body motion. Yet the practical impact of gaze dynamics on self-motion perception remains poorly understood. We tested how gaze position and gaze velocity shape self-motion perception--specifically heading direction--from visual signals in two behavioral experiments. In Experiment 1, we directly manipulated gaze position and velocity; in Experiment 2, a range of task demands evoked distinct gaze patterns. Across both experiments, heading estimates showed systematic, gaze-dependent errors: these estimates shifted toward the direction of eye motion and grew with horizontal gaze eccentricity and speed. A Bayesian ideal observer reproduced these error patterns across participants and tasks when it included three known features of visuomotor processing: (i) encoding retinal motion with eccentricity-dependent noise, (ii) underestimating eye-rotation speed, and (iii) a prior for moving straight ahead. These results reveal a lawful coupling between oculomotor behavior and heading perception. They further suggest that natural gaze strategies, such as keeping gaze near the optic-flow singularity and limiting pursuit speed, help mitigate gaze-dependent biases during navigation.

neuroscience↗

bioRxiv2025

SPECTRE-Plex: an automated, fast, high-resolution-enabled approach for multiplexed cyclic imaging and tissue spatial analysis

Mapping the spatial organization of tissues is critical to understanding organ biology in health and disease. Developments in multiplexed antibody-based, fluorescence labelling methods have provided unique insights into tissue microenvironments. However, many current methods have a variety of limitations that reduce their practical utilization. To address this, we developed SPECTRE-Plex; an end-to-end solution based on a series of methods that significantly improve speed, automation, and resolution of cyclic multiplex immunofluorescence imaging.

bioengineering↗

bioRxiv2016

Motivational, proteostatic and transcriptional deficits precede synapse loss, gliosis and neurodegeneration in the B6.HttQ111/+ model of Huntington’s disease

We investigated the appearance and progression of disease-relevant signs in the B6.HttQ111/+ mouse, a genetically precise model of the mutation that causes Huntingtons disease (HD). We find that B6.HttQ111/+ mice are healthy, show no overt signs of central or peripheral inflammation, and no gross motor impairment as late as 12 months of age. Behaviorally, we find that 4-9 month old B6.HttQ111/+ mice have normal activity levels and show no clear signs of anxiety or depression, but do show clear signs of reduced motivation. The neuronal density, neuronal size, synaptic density and number of glia is normal in B6.HttQ111/+ striatum, the most vulnerable brain region in HD, up to 12 months of age. Despite this preservation of the synaptic and cellular composition of the striatum, we observe clear progressive, striatal-specific, transcriptional dysregulation and accumulation of neuronal intranuclear inclusions (NIIs). Simulation studies suggest these molecular endpoints are sufficiently robust for future preclinical studies, and that B6.HttQ111/+ mice are a useful tool for modeling disease-modifying or neuroprotective strategies for disease processes before the onset of overt phenotypes.

neuroscience↗