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A high-throughput platform for single-molecule tracking identifies drug interaction and cellular mechanisms.
Elife
January 2025
Eikon Therapeutics Inc, Hayward, United States.
The regulation of cell physiology depends largely upon interactions of functionally distinct proteins and cellular components. These interactions may be transient or long-lived, but often affect protein motion. Measurement of protein dynamics within a cellular environment, particularly while perturbing protein function with small molecules, may enable dissection of key interactions and facilitate drug discovery; however, current approaches are limited by throughput with respect to data acquisition and analysis.
View Article and Find Full Text PDFA weight of evidence review on the mode of action, adversity, and the human relevance of xylene's observed thyroid effects in rats.
Crit Rev Toxicol
January 2025
Product Stewardship, Science & Regulatory, Shell Global Solutions International B.V. The Hague, the Netherlands.
Xylene substances have wide industrial and consumer uses and are currently undergoing dossier and substance evaluation under Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) for further toxicological testing including consideration of an additional neurotoxicological testing cohort to an extended one-generation reproduction toxicity (EOGRT) study. New repeated dose study data on xylenes identify the thyroid as a potential target tissue, and therefore a weight of evidence review is provided to investigate whether or not xylene-mediated changes on the hypothalamus-pituitary-thyroid (HPT) axis are secondary to liver enzymatic induction and are of a magnitude that is relevant for neurological human health concerns. Multiple published studies confirm xylene-mediated increases in liver weight, hepatocellular hypertrophy, and liver enzymatic induction the oral or inhalation routes, including an increase in uridine 5'-diphospho-glucuronosyltransferase (UDP-GT) activity, the key step in thyroid hormone metabolism in rodents.
View Article and Find Full Text PDFA mechanistic model for determining factors that influence inorganic nitrogen fate in corn cultivation.
Environ Sci Process Impacts
January 2025
Department of Civil and Environmental Engineering, University of Pittsburgh, Pittsburgh, PA, USA.
Conventional practices for inorganic nitrogen fertilizer are highly inefficient leading to excess nitrogen in the environment. Excess environmental nitrogen induces ecological (, hypoxia, eutrophication) and public health (, nitrate contaminated drinking water) consequences, motivating adoption of management strategies to improve fertilizer use efficiency. Yet, how to limit the environmental impacts from inorganic nitrogen fertilizer while maintaining crop yields is a persistent challenge.
View Article and Find Full Text PDFMapping 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 PDFDisruption of seasonal influenza circulation and evolution during the 2009 H1N1 and COVID-19 pandemics in Southeastern Asia.
Nat Commun
January 2025
School of Public Health, Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.
East, South, and Southeast Asia (together referred to as Southeastern Asia hereafter) have been recognized as critical areas fuelling the global circulation of seasonal influenza. However, the seasonal influenza migration network within Southeastern Asia remains unclear, including how pandemic-related disruptions altered this network. We leveraged genetic, epidemiological, and airline travel data between 2007-2023 to characterise the dispersal patterns of influenza A/H3N2 and B/Victoria viruses both out of and within Southeastern Asia, including during perturbations by the 2009 A/H1N1 and COVID-19 pandemics.
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