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Wachter, B.

Publications and source records attributed to Wachter, B..

3 recordsLinked to original sources

Bed and breakfast in the bush: Selection of resting sites and kill sites by leopards (Panthera pardus) on Namibian farmland

Sleeping and feeding are crucial for survival of any animal. In case of large predators, knowing where these activities occur can help us understand their behavioural adaptations for coexisting with people and could help mitigating human-carnivore conflicts. Leopard (Panthera pardus) is an elusive and highly adaptable large felid that mostly lives outside protected areas and can survive also in close proximity to humans. However, most leopard research in Africa has been conducted in protected areas and we poorly understand leopards habitat selection while resting and hunting. To shed light on their coexistence with humans, we investigated habitat features influencing leopard selection of resting and kill sites on farmlands in central Namibia, using generalized linear mixed models (GLMM) under a use-availability study design and blinded field-sampling. Leopards primarily selected resting sites that were located in mountainous, steep, rugged terrain and sites with good concealment while kill sites were selected in mountainous habitats. Human infrastructure did not affect leopard resting and kill site selection. Thus, the capacity of leopards to perform essential life-supporting behaviours while coexisting with people appears to be primarily driven by their ability to remain concealed, rather than spatially avoiding humans.

ecology↗

A spatial human thymus cell atlas mapped to a continuous tissue axis

T cells develop from circulating precursors, which enter the thymus and migrate throughout specialised sub-compartments to support maturation and selection. This process starts already in early fetal development and is highly active until the involution of the thymus in adolescence. To map the micro-anatomical underpinnings of this process in pre- vs. post-natal states, we undertook a spatially resolved analysis and established a new quantitative morphological framework for the thymus, the Cortico-Medullary Axis. Using this axis in conjunction with the curation of a multimodal single-cell, spatial transcriptomics and high-resolution multiplex imaging atlas, we show that canonical thymocyte trajectories and thymic epithelial cells are highly organised and fully established by post-conception week 12, pinpoint TEC progenitor states, find that TEC subsets and peripheral tissue genes are associated with Hassalls Corpuscles and uncover divergence in the pace and drivers of medullary entry between CD4 vs. CD8 T cell lineages. These findings are complemented with a holistic toolkit for spatial analysis and annotation, providing a basis for a detailed understanding of T lymphocyte development.

immunology↗

Constitutively active TrkB kinase signalling reduces actin filopodia dynamics and cell migration

Trk receptors and gene fusions of NTRK are targets in precision oncology. Classical Trk signalling concepts fail to explain ligand-independent signalling of intracellular TrkB or NTRK fusion proteins. Here, we show that abundance of the intracellular domain of TrkB is sufficient for ligand-independent autophosphorylation. This constitutive TrkB signalling reduced actin filopodia dynamics, could phosphorylate FAK, and changed cell morphology. Mutating Y705 in the kinase domain of TrkB alone specifically blocked these pathways. Engineered intracellular kinase domain proteins and a cancer-related intracellular NTRK2-fusion protein (SQSTM1-NTRK2) also underwent constitutive activation. In migrating glioblastoma-like U87MG cells, self-active TrkB kinase reduced cell migration. Moreover, we found evidences for constitutively active, intracellular TrkB in tissue of human grade IV glioblastoma. Structural modelling of the kinase domain let us postulate that release from cis-autoinhibition by abundance is sufficient for TrkB/FAK/Actin signalling via Y705. These constitutive signalling pathways could be fully blocked within minutes by clinically approved, anti-tumorigenic Trk inhibitors. In conclusion, our data provide an explanation and biological function for TrkB kinase domain signalling in the absence of a ligand.

neuroscience↗