Biology subjects

Noone, D.

Publications and source records attributed to Noone, D..

6 recordsLinked to original sources

bioRxiv2025

Direct cerebellar control over motor production in a species with extreme cerebellar enlargement

The cerebellum is thought to fine-tune movement without being required for its production. However, this textbook view derives mainly from studies of mammalian species with highly developed cerebral cortices. Here we examined cerebellar function in the elephant-nose fish, a member of a family of African weakly electric fish (Mormyridae) in which the cerebellum is massively enlarged. The elephant-nose fish is named for a flexible facial appendage that is used to probe surfaces and extract prey from substrate. Results from microstimulation, electrophysiological recordings, and lesions support a direct role for the C1 region of the mormyrid cerebellum in controlling movement of this appendage. These findings suggest that the cerebellum is capable of performing functions typically ascribed to the cerebral cortex, emphasizing the importance of evolutionary history on the functional specialization of brain regions.

neuroscience↗

bioRxiv2025

Alpha modulation of spiking activity across multiple brain regions in mice performing a tactile selective detection task

Many cognitive and sensory processes are characterized by strong relationships between the timing of neuronal spiking and the phase of ongoing local field potential oscillations. The coupling of neuronal spiking in neocortex to the phase of alpha oscillations (8-12 Hz) has been well studied in nonhuman primates but remains largely unexplored in other mammals. How this alpha modulation of spiking differs between brain areas and cell types, as well as its role in sensory processing and decision making, are not well understood. We used Neuropixels 1.0 probes to chronically record neural activity from somatosensory cortex, prefrontal cortex, striatum, and amygdala in mice performing a whisker-based selective detection task. We observed strong spontaneous alpha modulation of single-neuron spiking activity during inter-trial intervals while mice performed the task. The prevalence and strength of alpha phase modulation differed significantly across regions and between cell types. Phase modulated neurons exhibited stronger responses to both go and no-go stimuli, as well as stronger motor- and reward-related changes in firing rate, than their unmodulated counterparts. The increased responsiveness of phase modulated neurons suggests they are innervated by more diverse populations. Alpha modulation of neuronal spiking during baseline activity also correlated with task performance. In particular, many neurons exhibited strong alpha modulation before correct trials, but not before incorrect trials. These data suggest that dysregulation of spiking activity with respect to alpha oscillations may characterize lapses in attention.

neuroscience↗

bioRxiv2025

The MicroMap is a network visualisation resource for microbiome metabolism

The human microbiome plays a crucial role in metabolism and thereby influences health and disease. Constraint-based reconstruction and analysis (COBRA) has proven an attractive framework to generate mechanism-derived hypotheses along the nutrition-host-microbiome-disease axis within the computational systems biology community. Unlike for human, no large-scale visualisation resource for microbiome metabolism has been available to date. To address this gap, we created the MicroMap, a manually curated microbiome metabolic network visualisation, which captures the metabolic content of over a quarter million microbial genome-scale metabolic reconstructions. The MicroMap contains 5,064 unique reactions and 3,499 unique metabolites, including for 98 drugs. The MicroMap allows users to intuitively explore microbiome metabolism, inspect microbial metabolic capabilities, and visualise computational modelling results. Further, the MicroMap shall serve as an educational tool to make microbiome metabolism accessible to broader audiences beyond computational modellers. For example, we utilised the MicroMap to generate a comprehensive collection of 257,429 visualisations, corresponding to the entire scope of our current microbiome reconstruction resources, to enable users to visually compare and contrast the metabolic capabilities for diaerent microbes. The MicroMap seamlessly integrates with the Virtual Metabolic Human (VMH, www.vmh.life) and the COBRA Toolbox (opencobra.github.io), and is freely accessible at the MicroMap dataverse (https://dataverse.harvard.edu/dataverse/micromap), in addition to all the generated reconstruction visualisations.

systems biology↗

bioRxiv2024

Structural basis for surface activation of the classical complement cascade by the short pentraxin C-reactive protein

Human C-reactive protein (CRP) is a pentameric complex involved in defence against pathogens and regulation of autoimmunity. CRP is also a therapeutic target, with both administration and depletion of serum CRP being pursued as a possible treatment for autoimmune and cardiovascular diseases, among others. CRP binds to phosphocholine (PC) moieties on membranes in order to activate the complement system via the C1 complex, but it is unknown how CRP, or any pentraxin, binds to C1. Here, we present a cryo-electron tomography (cryoET)-derived structure of CRP bound to PC ligands and the C1 complex. To gain control of CRP binding, a synthetic mimotope of PC was synthesised and used to decorate cell-mimetic liposome surfaces. Structure-guided mutagenesis of CRP yielded a fully-active complex able to bind PC-coated liposomes that was ideal for cryoET and subtomogram averaging. In contrast to antibodies, which form Fc-mediated hexameric platforms to bind and activate the C1 complex, CRP formed rectangular platforms assembled from four laterally-associated CRP pentamers that bind only four of the six available globular C1 head groups. Potential residues mediating lateral association of CRP were identified from interactions between unit cells in existing crystal structures, which rationalised previously unexplained mutagenesis data regarding CRP-mediated complement activation. The structure also enabled interpretation of existing biochemical data regarding interactions mediating C1 binding, and identified additional residues for further mutagenesis studies. These structural data therefore provide a possible mechanism for regulation of complement by CRP, which limits complement progression and has consequences for how the innate immune system influences autoimmunity. Significance statementHuman C-reactive protein (CRP) activates the complement system to protect us from infections, but can also contribute towards progression of cardiovascular and autoimmune diseases when erroneously activated. To understand these processes, the authors used cryo-electron tomography to solve the in situ structure of surface-bound CRP interacting with the complement C1 complex. The structure revealed new interfaces that explain previous, sometimes contradictory, biochemical data. Comparisons with existing structures of antibody-mediated C1 activation revealed distinct structural differences that may explain how CRP modulates complement activity. Together, these structural data identify residues for mutagenesis to gain control over CRP functions, and provide new routes for future therapeutic developments.

immunology↗

bioRxiv2023

Lightning Pose: improved animal pose estimation via semi-supervised learning, Bayesian ensembling, and cloud-native open-source tools

Contemporary pose estimation methods enable precise measurements of behavior via supervised deep learning with hand-labeled video frames. Although effective in many cases, the supervised approach requires extensive labeling and often produces outputs that are unreliable for downstream analyses. Here, we introduce "Lightning Pose," an efficient pose estimation package with three algorithmic contributions. First, in addition to training on a few labeled video frames, we use many unlabeled videos and penalize the network whenever its predictions violate motion continuity, multiple-view geometry, and posture plausibility (semi-supervised learning). Second, we introduce a network architecture that resolves occlusions by predicting pose on any given frame using surrounding unlabeled frames. Third, we refine the pose predictions post-hoc by combining ensembling and Kalman smoothing. Together, these components render pose trajectories more accurate and scientifically usable. We release a cloud application that allows users to label data, train networks, and predict new videos directly from the browser.

neuroscience↗

bioRxiv2018

A High-Resolution Luminescent Assay For Rapid And Continuous Monitoring Of Protein Translocation Across Biological Membranes

Protein translocation is a fundamental process in biology. Major gaps in our understanding of this process arises due the poor sensitivity, low time-resolution and irreproducibility of translocation assays. To address this, we applied NanoLuc split-luciferase to produce a new strategy for measuring protein transport. The system reduces the timescale of data collection from days to minutes, and allows continuous acquisition with a time-resolution in the order of seconds - yielding kinetics parameters suitable for mechanistic elucidation and mathematical fitting. To demonstrate its versatility, we implemented and validated the assay in vitro and in vivo for the bacterial Sec system, and the mitochondrial protein import apparatus. Overall, this technology represents a major step forward, providing a powerful new tool for fundamental mechanistic enquiry of protein translocation and for inhibitor (drug) screening, with an intensity and rigour unattainable through classical methods.

biochemistry↗