Biology subjects

Travers, L.

Publications and source records attributed to Travers, L..

3 recordsLinked to original sources

bioRxiv2026

Ultrastructural remodelling of tau fibrils during ghost tangle formation in Alzheimer's disease brain

Tau aggregation into intracellular neurofibrillary tangles (NFTs) is one of the major hallmarks of Alzheimers disease (AD). Based on neuropathological studies, NFTs have been classified into pre-tangles, mature tangles, and ghost tangles, however the ultrastructural transitions between these stages remain poorly understood. Here, we used correlative light and electron microscopy (CLEM) to structurally characterize tau tangle maturity states in post-mortem human AD brain tissue. Pre-tangles showed no consistent fibrillar ultrastructure. Mature tangles contained densely packed, highly aligned paired helical filaments (PHF) and straight filaments (SF), often organized in spatially distinct bundles within the neuronal soma. Ghost tangles lacked cellular organelles and were composed predominantly of thin fibrils compartmentalized by membranous structures, with fibril morphology differing between compartmentalized and non-compartmentalized regions. Electron tomography and fibril segmentation demonstrated that these fibrils were significantly thinner than PHFs and SFs while immunogold labeling using the 2E9 tau marker confirmed the presence of tau within both mature and ghost tangle fibrils. GFAP-positive astrocytic processes infiltrated fibril-rich compartments within ghost tangles, linking astrocytic engagement with the emergence of this distinct ultrastructural organization. Together, our findings show that ghost-tangles contain a structurally distinct population of tau fibrils, suggesting that tau aggregates undergo astrocytic-mediated structural remodeling at late stages of pathology.

pathology↗

bioRxiv2026

Arginine Kinase 1 regulates energy homeostasis in Drosophila muscle development

In Drosophila, Arginine kinase 1 (Argk1) is involved in maintaining ATP homeostasis during bursts of activity in tissues with high and variable rates of energy turnover such as muscle. However, its role beyond stress conditions is less understood. Here, we show that Argk1 maintains energy homeostasis during flight muscle development and is required for animal viability and proper muscle function. The knockdown of Argk1 causes defects in both early and late stages of myogenesis. In the proliferating myoblasts associated with the wing disc, Argk1 depletion results in a reduction in cell size without changes in cell cycle progression. Single cell RNA-sequencing revealed that the overall composition of differentiating and undifferentiating myoblasts is not altered. Nonetheless, Argk1 knockdown causes broad alterations in the expression of genes involved in various metabolic pathways. This correlates with low levels in both ATP content and NAD+/NADH ratio. Later in muscle development, Argk1-depleted muscles completely lack spontaneous muscle contractions that are essential in myofibrillogenesis. Accordingly, Argk1 knockdown results in severe defects in sarcomere structure, while the mitochondrial network is highly fragmented. Furthermore, muscle growth is severely reduced. Thus, our data reveal an essential role for Argk1 in maintaining energy homeostasis throughout muscle development, which is required to meet the demand to support myofibrillogenesis, muscle growth and proper muscle function.

developmental biology↗

bioRxiv2019

Genetic integration of the stress response

The vertebrate stress response comprises a suite of behavioural and physiological traits that must be functionally integrated to ensure organisms cope adaptively with acute stressors. Natural selection should favour functional integration, leading to a prediction of genetic integration of these traits. Despite the implications of such genetic integration for our understanding of human and animal health, as well as evolutionary responses to natural and anthropogenic stressors, formal quantitative genetic tests of this prediction are lacking. Here we demonstrate that acute stress response components in Trinidadian guppies are both heritable and integrated on the major axis of genetic covariation. This integration could either facilitate or constrain evolutionary responses to selection, depending upon the alignment of selection with this axis. Such integration also suggests artificial selection on the genetically correlated behavioural responses to stress could offer a viable non-invasive route to the improvement of health and welfare in captive animal populations.

evolutionary biology↗