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Ladakis, D.

Publications and source records attributed to Ladakis, D..

2 recordsLinked to original sources

Depositing biological segmentation datasets FAIRly

Segmentation of biological images identifies regions of an image which correspond to specific features of interest, which can be analysed quantitatively to answer biological questions. This task has long been a barrier to conducting large-scale biological imaging studies as it is time- and labour-intensive. Modern artificial intelligence segmentation tools can automate this process, but require high quality segmentation data for training, which is challenging to acquire. Biological segmentation data has been produced for many years, but this data is not often reused to develop new tools as it is hard to find, access, and use. Recent disparate efforts (Iudin, et al., 2023; Xu, et al., 2021; Vogelstein, et al., 2018; Ermel, et al., 2024) have been made to facilitate deposition and re-use of these valuable datasets, but more work is needed to increase re-usability. In this work, we review the current state of publicly available annotation and segmentation datasets and make specific recommendations to increase re-usability following FAIR (findable, accessible, interoperable, re-usable) principles (Wilkinson, et al., 2016) for the future.

bioinformatics↗

Restoring the Multiple Sclerosis Associated Imbalance of Gut Indole Metabolites Promotes Remyelination and Suppresses Neuroinflammation

In multiple sclerosis (MS) the circulating metabolome is dysregulated, with indole lactate (ILA) being one of the most significantly reduced metabolites. We demonstrate that oral supplementation of ILA impacts key MS disease processes in two preclinical models. ILA reduces neuroinflammation by dampening immune cell activation as well as infiltration; and promotes remyelination and in vitro oligodendrocyte differentiation through the aryl hydrocarbon receptor (AhR). Supplementation of ILA, a reductive indole metabolite, restores the gut microbiomes oxidative/reductive metabolic balance by lowering circulating indole acetate (IAA), an oxidative indole metabolite, that blocks remyelination and oligodendrocyte maturation. The ILA-induced reduction in circulating IAA is linked to changes in IAA-producing gut microbiota taxa and pathways that are also dysregulated in MS. Notably, a lower ILA:IAA ratio correlates with worse MS outcomes. Overall, these findings identify ILA as a potential anti-inflammatory remyelinating agent and provide insights into the role of gut dysbiosis-related metabolic alterations in MS progression. One Sentence SummaryIndole lactate, a postbiotic metabolite reduced in MS, corrects gut microbiome metabolic imbalances associated with remyelination and neuroinflammation.

neuroscience↗