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Mapping the developmental trajectory of human astrocytes reveals divergence in glioblastoma.
Nat Cell Biol
January 2025
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Glioblastoma (GBM) is defined by heterogeneous and resilient cell populations that closely reflect neurodevelopmental cell types. Although it is clear that GBM echoes early and immature cell states, identifying the specific developmental programmes disrupted in these tumours has been hindered by a lack of high-resolution trajectories of glial and neuronal lineages. Here we delineate the course of human astrocyte maturation to uncover discrete developmental stages and attributes mirrored by GBM.
View Article and Find Full Text PDFStargardt disease is a currently untreatable, inherited neurodegenerative disease that leads to macular degeneration and blindness due to loss-of-function mutations in the ABCA4 gene. We have designed a dual adeno-associated viral vector encoding a split-intein adenine base editor to correct the most common mutation in ABCA4 (c.5882G>A, p.
View Article and Find Full Text PDFA decade of advances in human gut microbiome-derived biotherapeutics.
Nat Microbiol
January 2025
Sitala Bio, Cambridge, UK.
Microbiome science has evolved rapidly in the past decade, with high-profile publications suggesting that the gut microbiome is a causal determinant of human health. This has led to the emergence of microbiome-focused biotechnology companies and pharmaceutical company investment in the research and development of gut-derived therapeutics. Despite the early promise of this field, the first generation of microbiome-derived therapeutics (faecal microbiota products) have only recently been approved for clinical use.
View Article and Find Full Text PDFPredicting cell morphological responses to perturbations using generative modeling.
Nat Commun
January 2025
Department of Computational Health, Institute of Computational Biology, Helmholtz Zentrum München, Munich, Germany.
Advancements in high-throughput screenings enable the exploration of rich phenotypic readouts through high-content microscopy, expediting the development of phenotype-based drug discovery. However, analyzing large and complex high-content imaging screenings remains challenging due to incomplete sampling of perturbations and the presence of technical variations between experiments. To tackle these shortcomings, we present IMage Perturbation Autoencoder (IMPA), a generative style-transfer model predicting morphological changes of perturbations across genetic and chemical interventions.
View Article and Find Full Text PDFMenthol-based Novel Ultra-Deformable Vesicle: Formulation, Optimization and Evaluation of an Antifungal Drug.
AAPS PharmSciTech
January 2025
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576107, India.
The current study aims to establish a novel ultra-deformable vesicular system to enhance the drug penetration across the skin by preparing the ketoconazole-loaded menthosomes. It was achieved through regular thin-film evaporation & hydration techniques. To examine the effect of formulation parameters on menthosome characteristics, a 2 full factorial design was used using Design-Expert® software.
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