Biology subjects

Oates, A.

Publications and source records attributed to Oates, A..

5 recordsLinked to original sources

bioRxiv2025

TopoTome: Topology-informed unsupervised segmentation and analysis of 3D images

Biological systems are three-dimensional and complex. Today, images of biological structures can be acquired using different imaging technologies and at increasing resolutions. However, identifying relevant structural features in three-dimensional (3D) images remains a significant challenge. 3D image segmentation is usually performed using deep-learning segmentation models. Such models are trained on manually annotated and segmented, dataset-specific images. Consequently, they rarely generalize across datasets. Here, we overcome these limitations with TopoTome, an unsupervised 3D image segmentation and analysis algorithm. TopoTome is based on topological data analysis, and conceptually distinct from standard clustering and deep learning image analysis models. It encodes the 3D image directly in topological space. Then, it performs unsupervised clustering to detect and segment features represented by salient and spatially coherent voxel intensity gradients. We demonstrate on simple, complex, synthetic and real-world 3D image data that it outperforms all 3D clustering algorithms. Its segmentation ranks with or outperforms best-in-class deep learning 3D image segmentation software. Beyond image segmentation, it provides streamlined topological data analysis of 3D images, advancing 3D image analysis from conventional mesh volumetry to structural topology. Owing to its conceptually different topological data analysis core, TopoTome does not need prior information and tuning to generalize across different imaging modalities, including fluorescence microscopy and X-ray computed tomography. We show it also readily generalizes across biological subjects, such as different species, organs and cells. TopoTome is thus one of the most versatile and accurate unsupervised 3D image segmentation algorithms.

bioinformatics↗

bioRxiv2023

Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform

Drug repurposing is an important strategy in COVID-19 treatment, but many clinically approved compounds have not been extensively studied in the context of embryogenesis, thus limiting their administration during pregnancy. Here we used the zebrafish embryo model organism to test the effects of 162 marketed drugs on cardiovascular development. Among the compounds used in the clinic for COVD-19 treatment, we found that Remdesivir led to reduced body size and heart functionality at clinically relevant doses. Ritonavir and Baricitinib showed reduced heart functionality and Molnupiravir and Baricitinib showed effects on embryo activity. Sabizabulin was highly toxic at concentrations only 5 times higher than Cmax and led to a mean mortality of 20% at Cmax. Furthermore, we tested if zebrafish could be used as a model to study inflammatory response in response to spike protein treatment and found that Remdesivir, Ritonavir, Molnupiravir, Baricitinib as well as Sabizabulin counteracted the inflammatory response related gene expression upon SARS-CoV-2 spike protein treatment. Our results show that the zebrafish allows to study immune-modulating properties of COVID-19 compounds and highlights the need to rule out secondary defects of compound treatment on embryogenesis. All results are available on a user friendly web-interface https://share.streamlit.io/alernst/covasc_dataapp/main/CoVasc_DataApp.py that provides a comprehensive overview of all observed phenotypic effects and allows personalized search on specific compounds or group of compounds. Furthermore, the presented platform can be expanded for rapid detection of developmental side effects of new compounds for treatment of COVID-19 and further viral infectious diseases. Summary statementA zebrafish screening platform assesses side effects on cardiovascular development and behavior of FDA approved drugs used in clinical practice to treat COVID-19 and their immune modulatory effect upon spike protein treatment.

developmental biology↗

bioRxiv2021

Ipsilesional motor cortex activation with high-force unimanual handgrip contractions of the less-affected limb in participants with stroke

Stroke is a leading cause of severe disability that often presents with unilateral motor impairment. Conventional rehabilitation approaches focus on motor practice of the affected limb and aim to suppress brain activity in the contralesional hemisphere to facilitate ipsilesional hemispheric neuroplasticity subserving motor recovery. Previous research has also demonstrated that exercise of the less-affected limb can promote motor recovery of the affected limb through the interlimb transfer of the trained motor task, termed cross-education. One of the leading theories for cross-education proposes that the interlimb transfer manifests from ipsilateral cortical activity during unimanual motor tasks, and that this ipsilateral cortical activity results in motor related neuroplasticity giving rise to contralateral improvements in motor performance. Conversely, exercise of the less-affected limb promotes contralesional brain activity which is typically viewed as contraindicated in stroke recovery due to the interhemispheric inhibitory influence onto the ipsilesional hemisphere. High-force unimanual handgrip contractions are known to increase ipsilateral brain activation in control participants, but it remains to be determined if this would be observed in participants with stroke. Therefore, this study aimed to determine how parametric increases in handgrip force during repeated contractions with the less-affected limb impacts brain activity bilaterally in participants with stroke and in a cohort of neurologically intact controls. In this study, higher force contractions were found to increase brain activation in the ipsilesional/ipsilateral hemisphere in both groups (p = .002), but no between group differences were observed. These data suggest that high-force exercise with the less-affected limb may promote ipsilesional cortical plasticity to promote motor recovery of the affected-limb in participants with stroke.

neuroscience↗

bioRxiv2020

From local resynchronization to global pattern recovery in the zebrafish segmentation clock

ABSTRACTRhythmic spatial gene expression patterns termed the segmentation clock regulate vertebrate body axis segmentation during embryogenesis. The integrity of these patterns requires local synchronization between neighboring cells by Delta-Notch signaling and its inhibition results in defective segment boundaries. The oscillating tissue deforms substantially throughout development, but whether such tissue-scale morphogenesis complements local synchronization during pattern generation and segment formation is not understood. Here, we investigate pattern recovery in the zebrafish segmentation clock by washing out a Notch inhibitor, allowing resynchronization at different developmental stages, and analyzing the recovery of normal segments. Although from previous work no defects are expected after recovery, we find that washing out at early stages causes a distinctive intermingling of normal and defective segments, suggesting unexpectedly large fluctuations of synchrony before complete recovery. To investigate this recovery behavior, we develop a new model of the segmentation clock combining key ingredients motivated by prior experimental observations: coupling between neighboring oscillators, a frequency profile, a gradient of cell mixing, tissue length change, and cell advection pattern. This model captures the experimental observation of intermingled normal and defective segments through the formation of persistent phase vortices of the genetic oscillators. Experimentally observed recovery patterns at different developmental stages are predicted by temporal changes of tissue-level properties, such as tissue length and cell advection pattern in the model. These results suggest that segmental pattern recovery occurs at two scales: local pattern formation and transport of these patterns through tissue morphogenesis, highlighting a generic mechanism of pattern dynamics within developing tissues.SIGNIFICANCE Interacting genetic oscillators can generate a coherent rhythm and a tissue-level pattern from an initially desynchronized state. Using experiment and theory we study resynchronization and pattern recovery of the zebrafish segmentation clock, which makes the embryonic body segments. Experimental perturbation of intercellular signaling with an inhibitor results in intermingled normal and defective segments. According to theory, this behavior may be caused by persistent local vortices scattered in the tissue during pattern recovery. Full pattern recovery follows dynamic global properties, such as tissue length and advection pattern, in contrast to other genetic oscillators in a static tissue such as circadian clocks. Our work highlights how dynamics of tissue level properties may couple to biochemical pattern formation in tissues and developing embryos.Competing Interest StatementThe authors have declared no competing interest.View Full Text

developmental biology↗

bioRxiv2019

Do direct nose-to-brain pathways underlie intranasal oxytocin-induced changes in regional cerebral blood flow in humans?

Could nose-to-brain pathways mediate the effects of peptides such as oxytocin (OT) on brain physiology when delivered intranasally? We address this question by contrasting two methods of intranasal administration (a standard nasal spray, and a nebulizer expected to improve OT deposition in nasal areas putatively involved in direct nose-to-brain transport) to intravenous administration in terms of effects on regional cerebral blood flow during two hours post-dosing. We demonstrate that OT-induced decreases in amygdala perfusion, a key hub of the OT central circuitry, are explained entirely by OT increases in systemic circulation following both intranasal and intravenous OT administration. Yet we also provide robust evidence confirming the validity of the intranasal route to target specific brain regions. Our work has important translational implications and demonstrates the need to carefully consider the method of administration in our efforts to engage specific central oxytocinergic targets for the treatment of neuropsychiatric disorders.

neuroscience↗