Biology subjects

Becker, T.

Publications and source records attributed to Becker, T..

4 recordsLinked to original sources

bioRxiv2018

Regeneration of dopaminergic neurons in adult zebrafish depends on immune system activation and differs for distinct populations

Adult zebrafish regenerate neurons in their brain, but the extent and variability of this capacity is unclear. Here we ask whether loss of various dopaminergic neuron populations is sufficient to trigger their functional regeneration. Genetic lineage tracing shows that specific diencephalic ependymo-radial glial progenitor cells (ERGs) give rise to new dopaminergic (Th+) neurons. Ablation elicits an immune response, increased proliferation of ERGs and increased addition of new Th+ neurons in populations that constitutively add new neurons, e.g. diencephalic population 5/6. Inhibiting the immune response attenuates neurogenesis to control levels. Boosting the immune response enhances ERG proliferation, but not addition of Th+ neurons. In contrast, in populations in which constitutive neurogenesis is undetectable, e.g. the posterior tuberculum and locus coeruleus, cell replacement and tissue integration are incomplete and transient. This is associated with loss of spinal Th+ axons, as well as permanent deficits in shoaling and reproductive behaviour. Hence, dopaminergic neuron populations in the adult zebrafish brain show vast differences in regenerative capacity that correlate with constitutive addition of neurons and depend on immune system activation.

neuroscience↗

bioRxiv2018

Evaluation of Deep Learning Strategies for Nucleus Segmentation in Fluorescence Images

Identifying nuclei is often a critical first step in analyzing microscopy images of cells, and classical image processing algorithms are most commonly used for this task. Recent developments in deep learning can yield superior accuracy, but typical evaluation metrics for nucleus segmentation do not satisfactorily capture error modes that are relevant in cellular images. Besides, large image data sets with ground truth for evaluation have been limiting. We present an evaluation framework to measure accuracy, types of errors, and computational efficiency; and use it to compare two deep learning strategies (U-Net and DeepCell) alongside a classical approach implemented in CellProfiler. We publicly release a set of 23,165 manually annotated nuclei and source code to reproduce experiments. Our results show that U-Net outperforms both pixel-wise classification networks and classical algorithms. Also, our evaluation framework shows that deep learning improves accuracy and reduces the number of biologically relevant errors by half.

bioinformatics↗

bioRxiv2018

Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages is necessary for functional spinal cord regeneration in zebrafish

Spinal cord injury leads to a massive response of innate immune cells (microglia, macrophages, neutrophils) both, in non-regenerating mammals and in successfully regenerating zebrafish, but the role of these immune cells in functional spinal cord regeneration in zebrafish has not been addressed. Here we show that inhibiting inflammation reduces and promoting it accelerates axonal regeneration in larval zebrafish. Mutant analyses show that peripheral macrophages, but not neutrophils or microglia, are necessary and sufficient for full regeneration. Macrophage-less irf8 mutants show prolonged inflammation with elevated levels of Il-1{beta} and Tnf-. Decreasing Il-1{beta} levels or number of Il-1{beta}+ neutrophils rescues functional regeneration in irf8 mutants. However, during early regeneration, interference with Il-1{beta} function impairs regeneration in irf8 and wildtype animals. Inhibiting Tnf- does not rescue axonal growth in irf8 mutants, but impairs it in wildtype animals, indicating a pro-regenerative role of Tnf-. Hence, inflammation is tightly and dynamically controlled by macrophages to promote functional spinal cord regeneration in zebrafish.

developmental biology↗

bioRxiv2017

A novel mitochondrial enriched antioxidant protects neurons against acute oxidative stress

Excessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinsons disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches. We show that, while it has radical scavenging ability on par with other flavonoids in a cell-free system, Proxison is orders of magnitude more potent than natural flavonoids at protecting neural cells against oxidative stress and is capable of rescuing damaged cells. The unique combination of a lipophilic hydrocarbon tail with a modified polyphenolic head group promotes efficient cellular uptake and mitochondrial localisation of Proxison. Importantly, in vivo administration of Proxison demonstrated effective and well tolerated neuroprotection against oxidative stress in a zebrafish model of dopaminergic neuronal loss.

cell biology↗