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Sphingolipids are pivotal for plant development and stress responses. Growing interest has been directed towards fully comprehending the regulatory mechanisms of the sphingolipid pathway. We explore its biosynthesis and homeostasis in cell cultures, shedding light on fundamental metabolic mechanisms. Employing N isotope labeling and quantitative dynamic modeling approach, we developed a egularized and constraint-based ynamic etabolic lux nalysis (r-DMFA) framework to predict metabolic shifts due to enzymatic changes. Our analysis revealed key enzymes such as sphingoid-base hydroxylase (SBH) and long-chain-base kinase (LCBK) to be critical for maintaining sphingolipid homeostasis. Disruptions in these enzymes were found to affect cellular viability and increase the potential for programmed cell death (PCD). Thus, this work enhances our understanding of sphingolipid metabolism and demonstrates the utility of dynamic modeling in analyzing complex metabolic pathways.
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http://dx.doi.org/10.1101/2023.12.08.570827 | DOI Listing |
Acta Neuropathol Commun
September 2025
Department of Biomedical and Clinical Sciences and Department of Clinical Pathology, Linköping University, 58185, Linköping, Sweden.
Disruptions in synaptic transmission and plasticity are early hallmarks of Alzheimer's disease (AD). Endosomal trafficking, mediated by the retromer complex, is essential for intracellular protein sorting, including the regulation of amyloid precursor protein (APP) processing. The VPS35 subunit, a key cargo-recognition component of the retromer, has been implicated in neurodegenerative diseases, with mutations such as L625P linked to early-onset AD.
View Article and Find Full Text PDFPulm Ther
September 2025
Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55216, Ingelheim am Rhein, Germany.
Introduction: The modification of an inhaler's air flow resistance influences a patient's inhalation flow profile, thereby affecting the exit velocity of an aerosol leaving the Respimat® mouthpiece. A slower inhalation maneuver results in reduced plume velocity and thus a decreased oropharyngeal deposition due to reduced impaction. This could not only lead to fewer unwanted side effects associated with inhaled therapies, but also enhance lung deposition.
View Article and Find Full Text PDFNature
September 2025
Centre for Evolution and Cancer, Institute of Cancer Research, London, UK.
Cancer development and response to treatment are evolutionary processes, but characterizing evolutionary dynamics at a clinically meaningful scale has remained challenging. Here we develop a new methodology called EVOFLUx, based on natural DNA methylation barcodes fluctuating over time, that quantitatively infers evolutionary dynamics using only a bulk tumour methylation profile as input. We apply EVOFLUx to 1,976 well-characterized lymphoid cancer samples spanning a broad spectrum of diseases and show that initial tumour growth rate, malignancy age and epimutation rates vary by orders of magnitude across disease types.
View Article and Find Full Text PDFMicrobes Environ
September 2025
Sustainable Process Engineering Center, Department of Chemical Engineering, Faculty of Engineering, Universiti Malaya.
Nitrifying communities in activated sludge play a crucial role in biological nitrogen removal processes in municipal wastewater treatment plants. While extensive research has been conducted in temperate regions, limited information is available on nitrifiers in tropical regions. The present study investigated all currently known nitrifying communities in two full-scale municipal wastewater treatment plants in Malaysia operated under low-dissolved oxygen (DO) (0.
View Article and Find Full Text PDFNucleic Acids Res
September 2025
Department of Chemistry and Henry Eyring Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112, United States.
Glycine is an important metabolite and cell signal in diverse organisms, yet tools to visualize intracellular glycine dynamics have not been developed. In this study, diverse and bright RNA-based glycine biosensors were developed by fusing the architecturally complex glycine riboswitch with Broccoli class fluorogenic aptamers. The brightest sensor with the highest activation, glyS, and its two-dye ratiometric counterpart, Pepper-glyS, allowed for visualization of a drug-induced accumulation of endogenous glycine in live Escherichia colicells.
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