Biology subjects

Cooper, E. A.

Publications and source records attributed to Cooper, E. A..

10 recordsLinked to original sources

bioRxiv2026

Ependymomas are cancers of the pre-neural crest/roof plate lineage

Distinct molecular variants of the brain cancer ependymoma are distributed along the rostral-caudal extent of the central nervous system (CNS). Historically proposed to arise from ventricular ependyma, recent studies have suggested conflicting cellular origins, including the neural radial glia and the roof plate lineages. Using single-cell transcriptomics, immunohistochemistry, and lineage tracing, we demonstrate that ependymomas across all CNS compartments transcriptionally mirror MSX1+ve pre-neural crest/roof plate (Pre-NC/RP) lineage derivatives. Ependymoma subgroups recapitulate the spatial and molecular diversity of regional Pre-NC/RP populations, while retaining conserved MSX1 expression. Expression of the oncogenic fusion ZFTA-RELA within the murine Pre-NC/RP lineage generated tumors that faithfully resembled human ependymoma. These findings identify a common embryonic cellular origin for ependymomas and reconcile previously conflicting models of tumorigenesis.

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

Childhood brain tumours instruct cranial haematopoiesis and immunotolerance

Recent research has revealed a remarkable role for immunosurveillance in healthy and diseased brains, dispelling the notion that this organ is a passive immune-privileged site1-3. Better understanding of how this immunosurveillance operates could improve the treatment of neurological diseases. Here, using a novel genetically engineered mouse model of ZFTA-RELA ependymoma4-a childhood brain tumour-we characterised an immune circuit between the tumour and antigen presenting, haematopoietic stem/progenitor cells (HSPCs) in the skull bone marrow. The presentation of antigens in the cerebrospinal fluid (CSF) by HSPCs to CD4+ T cells, biased HSPC lineages toward myelopoiesis and polarised CD4+ T-cells to regulatory T cells (T- regs), culminating in tumour immunotolerance. Remarkably, a single infusion of antibodies directed against cytokines enriched in the CSF of mice bearing ZFTA-RELA ependymomas, choroid plexus carcinomas or Group-3 medulloblastoma-all aggressive childhood brain tumours-disrupted this process and caused profound tumour regression. These data unmask a mechanism by which skull bone marrow-derived HSPCs and CD4+ T cells cooperate to promote the immunotolerance of childhood brain tumours. Antibodies that disrupt this immunosurveillance could prove an effective therapy for these cancers that are less toxic than current treatments.

immunology↗

bioRxiv2025

Utilizing a pan-transcriptome reveals genotype-specific responses to iron deficiency in Sorghum bicolor

IntroductionSweet sorghum genotypes are distinguished from non-sweet types by their ability to accumulate high concentrations of sugar in their stems, which makes them valuable for both bioenergy production and as an alternative source of sugar. Previous work has reported numerous gene copy number differences in metal metabolism and iron transport genes between the sweet and non-sweet genotypes. The objective of this study was to investigate which genes are differentially expressed by the sweet and non-sweet genotypes under varying iron conditions. MethodsThree sweet and three non-sweet sorghum genotypes were grown hydroponically under two conditions (control and low iron), and root tissue from the plants was harvested for RNA extraction and sequencing after 9 days. To obtain a more complete picture of diverse iron-response mechanisms in sorghum, we constructed a pan-transcriptome from 10 founder parents of the Carbon-Partitioning Nested Association Mapping population. ResultsDifferential expression analysis using the pan-transcriptome revealed 209 genes that responded differently to iron stress in the sweet and non-sweet types, which was more than twice as many genes found using only a single reference genome. Enrichment analysis based on age of duplication event showed that duplicate gene copies that are differentially expressed due to genotype effect appear to be specific to sorghum while most duplicate gene copies that are differentially expressed due to iron treatment appear to be more evolutionary conserved across plants. DiscussionThis study highlights the importance of the non-core genome and the utility of the pan-transcriptome in sorghum. It also revealed that different sorghum genotypes respond to iron stress differently.

plant biology↗

bioRxiv2024

Climate Adaptation and Genetic Differentiation in the Mosquito Species Culex tarsalis

The increasing prevalence of vector-borne diseases around the world highlights the pressing need for an in-depth exploration of the genetic and environmental factors that shape the adaptability and widespread distribution of mosquito populations. This research focuses on Culex tarsalis, a principal vector for various viral diseases including West Nile Virus (WNV). Through the development of a new reference genome and the examination of Restriction-Site Associated DNA sequencing (RAD-seq) data from over 300 individuals and 28 locations, we demonstrate that variables such as temperature, evaporation rates, and the density of vegetation significantly impact the genetic makeup of Cx. tarsalis populations. Among the alleles most strongly associated with environmental factors is a nonsynonymous mutation in a key gene related to circadian rhythms. These results offer new insights into the mechanisms of spread and adaptation in a key North American vector species, which is poised to become a growing health threat to both humans and animals in the face of ongoing climate change.

genomics↗

bioRxiv2023

Transformations of sensory information in the brain reflect a changing definition of optimality

Neurons throughout the brain modulate their firing rate lawfully in response to changes in sensory input. Theories of neural computation posit that these modulations reflect the outcome of a constrained optimization: neurons aim to efficiently and robustly represent sensory information under resource limitations. Our understanding of how this optimization varies across the brain, however, is still in its infancy. Here, we show that neural responses transform along the dorsal stream of the visual system in a manner consistent with a transition from optimizing for information preservation to optimizing for perceptual discrimination. Focusing on binocular disparity - the slight differences in how objects project to the two eyes - we re-analyze measurements from neurons characterizing tuning curves in macaque monkey brain regions V1, V2, and MT, and compare these to measurements of the natural visual statistics of binocular disparity. The changes in tuning curve characteristics are computationally consistent with a shift in optimization goals from maximizing the information encoded about naturally occurring binocular disparities to maximizing the ability to support fine disparity discrimination. We find that a change towards tuning curves preferring larger disparities is a key driver of this shift. These results provide new insight into previously-identified differences between disparity-selective regions of cortex and suggest these differences play an important role in supporting visually-guided behavior. Our findings support a key re-framing of optimal coding in regions of the brain that contain sensory information, emphasizing the need to consider not just information preservation and neural resources, but also relevance to behavior. SignificanceA major role of the brain is to transform information from the sensory organs into signals that can be used to guide behavior. Neural activity is noisy and can consume large amount of energy, so sensory neurons must optimize their information processing so as to limit energy consumption while maintaining key behaviorally-relevant information. In this report, we re-examine classically-defined brain areas in the visual processing hierarchy, and ask whether neurons in these areas vary lawfully in how they represent sensory information. Our results suggest that neurons in these brain areas shift from being an optimal conduit of sensory information to optimally supporting perceptual discrimination during natural tasks.

neuroscience↗

bioRxiv2022

Ten new high-quality genome assemblies for diverse bioenergy sorghum genotypes

Sorghum (Sorghum bicolor (L.) Moench) is an agriculturally and economically important staple crop that has immense potential as a bioenergy feedstock due to its relatively high productivity on marginal lands. To capitalize on and further improve sorghum as a potential source of sustainable biofuel, it is essential to understand the genomic mechanisms underlying complex traits related to yield, composition, and environmental adaptations. Expanding on a recently developed mapping population, we generated de novo genome assemblies for 10 parental genotypes from this population and identified a comprehensive set of over 24 thousand large structural variants (SVs) and over 10.5 million single nucleotide polymorphisms (SNPs).These resources can be integrated into both ongoing and future mapping and trait discovery for sorghum and its myriad uses including food, feed, bioenergy, and increasingly as a carbon dioxide removal mechanism. We show that SVs and nonsynonymous SNPs are enriched in different gene categories, emphasizing the need for long read sequencing in crop species to identify novel variation. Furthermore, we highlight SVs and SNPs occurring in genes and pathways with known associations to critical bioenergy-related phenotypes and characterize the landscape of genetic differences between sweet and cellulosic genotypes.

genomics↗

bioRxiv2022

Low vision impairs implicit sensorimotor adaptation in response to small errors, but not large errors

Successful goal-directed actions require constant fine-tuning of the motor system. This fine-tuning is thought to rely on an implicit adaptation process that is driven by sensory prediction errors (i.e., where you see your hand after reaching versus where you expected it to be). Individuals with low vision experience challenges with visuomotor control, but whether they also experience challenges with implicit adaptation is unknown. To explore this question, we assessed individuals with low vision and matched controls with normal vision on a visuomotor task designed to isolate implicit adaptation. We found that low vision was associated with attenuated implicit adaptation only for small visual errors, but not large visual errors. This result not only underscores an unappreciated motor learning impairment associated with low vision, but also highlights an important constraint on how low-fidelity visual information is processed by the nervous system to enable successful implicit adaptation. New and NoteworthyWhether implicit adaptation is also impacted by visual uncertainty intrinsic to the nervous system remains unknown. To test this, we examined 20 people who live with visual uncertainty in daily life due to low vision on a visuomotor task that isolates implicit adaptation. We found that low vision attenuates adaptation in response to small errors only, paving the way for new developments in rehabilitation and assistive devices for individuals with sensory impairments.

neuroscience↗

bioRxiv2021

Individual differences in frontoparietal plasticity in humans

Neuroplasticity, defined as the brains potential to change in response to its environment, has been extensively studied at the cellular and molecular levels. Work in animal models suggests that stimulation to the ventral tegmental area (VTA) enhances plasticity, and that myelination constrains plasticity. Little is known, however, about whether proxy measures of these properties in the human brain are associated with learning. Here, we investigated the plasticity of the frontoparietal system by asking whether VTA resting-state functional connectivity and myelin map values (T1w/T2w ratios) predicted learning after short-term training on the adaptive n-back (n = 46, ages 18-25). We found that stronger baseline connectivity between VTA and lateral prefrontal cortex predicted greater improvements in accuracy. Lower myelin map values predicted improvements in response times, but not accuracy. Our findings suggest that proxy markers of neural plasticity can predict learning in humans.

neuroscience↗

bioRxiv2020

Natural image statistics at depth edges modulate perceptual stability

Binocular fusion relies on matching points in the two eyes that correspond to the same physical feature in the world. However, not all world features are binocularly visible. In particular, at depth edges parts of a scene are often visible to only one eye (so-called half occlusions). Accurate detection of these monocularly visible regions is likely to be important for stable visual perception. If monocular regions are not detected as such, the visual system may attempt to binocularly fuse non-corresponding points, which can result in unstable percepts. We investigated the hypothesis that the visual system capitalizes upon statistical regularities associated with depth edges in natural scenes to aid binocular fusion and facilitate perceptual stability. By sampling from a large set of stereoscopic natural image patches, we found evidence that monocularly visible regions near depth edges in natural scenes tend to have features more visually similar to the adjacent binocularly visible background region than to the adjacent binocularly visible foreground. The generality of these results was supported by a parametric study of three-dimensional (3D) viewing geometry in simulated environments. In two perceptual experiments, we examined if this statistical regularity may be leveraged by the visual system. The results show that perception tended to be more stable when the visual properties of the depth edge were statistically more likely. Exploiting regularities in natural environments may allow the visual system to facilitate fusion and perceptual stability of natural scenes when both binocular and monocular regions are visible. PrecisWe report an analysis of natural scenes and two perceptual studies aimed at understanding how the visual statistics of depth edges impact perceptual stability. Our results suggest that the visual system exploits natural scene regularities to aid binocular fusion and facilitate perceptual stability.

neuroscience↗