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Biology subjects

Merino, M.

Publications and source records attributed to Merino, M..

4 recordsLinked to original sources

A human-in-the-loop approach for faster cell tracking

Traditional cell tracking methods focus on fully automated tracking. The quality of the generated tracks, however, is heavily influenced by factors such as cell speed and density. In complex scenarios where track correctness is essential, an efficient and reliable tool for manual track correction remains a key component of the cell tracking process. Most tracking tools that allow for such manual correction do so only as a post-processing step, using human feedback to correct one track error at a time -- without improving the quality of other tracks in the dataset. This highlights the need for a more efficient track correction method that iteratively integrates human feedback into the automated tracking process. In this paper we propose a human-in-the-loop approach to cell tracking and investigate the extent to which a tracking algorithm can learn from human input during the tracking process. We combine a graph representation of cell detections, Dijkstra's shortest path algorithm, and a neural network that predicts cell displacement to generate initial track suggestions. We introduce a tool that enables human feedback on individual tracks suggested by the algorithm; this feedback is then propagated to improve subsequent track generation. Compared to the traditional approach of fully automated tracking with correction as a post-processing step, our human-in-the-loop tracking framework reduces the number of corrections required. Finally, we show how this approach can be integrated with existing state-of-the-art tracking algorithms by using pre-generated tracks as a prior, improving the quality of tracks suggested to the human annotator.

bioinformatics↗

Cooperative motility emerges in crowds of T cells but not neutrophils

Interacting, self-propelled particles are prone to jamming when crowded. This well-described phenomenon is shared by diverse systems including cars, animal colonies, and pedestrians. T cells, essential effectors of adaptive immunity, seemingly defy this principle: the rapid migration enabling their protective function persists even in tightly packed tissue environments - from the thymus where T cells develop, to lymphoid organs they survey for antigen, to tissues they clear from infection. Here we studied T cell crowds by combining experiments of T cells migrating in microfluidic devices with in silico models. We observed that while single T cells are highly heterogeneous in their motility, in crowds they synchronized their speeds and formed stable, motile trains. Our models showed that the emergence of this flocking-like behavior can be explained by a combination of two interaction mechanisms at the cell-cell interface: adhesion maintains cohesive T cell groups, and force transmission accelerates slower cells. Not all immune cells flock when they are crowded: neutrophils in the same settings slowed down with increasing cell density. Thus, cooperative motion may enable T cells to remain motile in densely packed tissue environments, preventing jams that curtail the motion of other crowded systems.

cell biology↗

DOCK8 regulates a mechanosensitive actin redistribution that maintains immune cell cohesion and protects the nucleus during migration

Immune cells navigate through complex 3-dimensional tissue architectures, utilizing an amoeboid mode of migration, characterized by extensive cellular deformation, low adhesion, and high cell velocities. In the absence of expression of Dedicator of Cytokinesis 8 (Dock8), a gene identified with loss-of-function mutations in immunodeficiency, cells become entangled during migration through dense, confined environments and consequently undergo catastrophic cell rupturing, while migration on 2D surfaces remains entirely intact. Here we investigated the specific cytoskeletal defect of Dock8-deficient activated T cells, showing that even prior to entanglement they display a striking difference in F-actin distribution compared to wild type (WT) cells. We describe a central pool of F-actin in WT murine and human T cells which is absent in Dock8 KO T cells, and determine that the relocalization of F-actin is a mechanoresponsive circuit, emerging only when cells are very confined. Our works shows that the central actin pool is nucleo-protective, reducing nuclear deformation and DNA damage during confined migration. We identify the Hippo-pathway kinase Mst1 as a co-mediator of this mechanosensitive pathway in conjunction with Dock8, allowing for cell cohesion and survival during migration through complex environments.

immunology↗

Exploration of the Ixodes ricinus virosphere unveils an extensive virus diversity including novel Coltiviruses and other reoviruses

Recent metagenomics studies have revealed several tick species to host a variety of previously undiscovered RNA viruses. Ixodes ricinus, which is known to be a vector for many viral, bacterial and protozoan pathogens, is the most prevalent tick species in Europe. For this study, we decided to investigate the virosphere of Belgian I. ricinus ticks. High-throughput sequencing of tick pools collected from six different sampling sites revealed the presence of viruses belonging to many different viral orders and families, including Mononegavirales, Bunyavirales, Partitiviridae and Reoviridae. Of particular interest was the detection of several new reoviruses, two of which cluster together with members of the genus Coltivirus. This includes a new strain of Eyach virus, a known causative agent of tick-borne encephalitis. All genome segments of this new strain are highly similar to those of previously published Eyach virus genomes, except for the fourth segment, encoding VP4, which is markedly more dissimilar, potentially indicating the occurrence of a genetic reassortment. Further PCR-based screening of over 230 tick pools for 14 selected viruses showed that most viruses could be found in all six sampling sites, indicating the wide spread of these viruses throughout the Belgian tick population. Taken together, these results illustrate the role of ticks as important virus reservoirs, highlighting the need for adequate tick control measures.

microbiology↗