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Understanding rapid, nonequilibrium dynamics of single proteins in lipid membranes is crucial but challenging. This study advances fluorescence lifetime analysis by developing a computationally efficient variational Bayesian framework for photon-by-photon hidden Markov modeling. It enables robust and accurate model selection, facilitating real-time tracking of state evolution of a molecule within a brief time frame. We applied the method to investigate nonequilibrium membrane insertion of a model peptide, revealing that unsaturated bonds in acyl chains not only merely modulate the fluidity of lipid membranes but also directly interact with transmembrane proteins, answering a long-standing question about unsaturated bonds' roles in membrane-protein interactions.
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http://dx.doi.org/10.1021/jacs.5c06452 | DOI Listing |
Sci Prog
September 2025
Shenzhen University Sixth Affiliated Hospital, Shenzhen Nanshan People's Hospital, Shenzhen, China.
Colorectal cancer ranks among the most prevalent and lethal malignant tumors globally. Historically, the incidence of colorectal cancer in China has been lower than that in developed European and American countries; however, recent trends indicate a rising incidence due to changes in dietary patterns and lifestyle. Lipids serve critical roles in human physiology, such as energy provision, cell membrane formation, signaling molecule function, and hormone synthesis.
View Article and Find Full Text PDFPsychopharmacology (Berl)
September 2025
Instituto de Biología Celular y Neurociencias "Prof. De Robertis" (IBCN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina.
Rationale: Autism spectrum disorders (ASD) are a group of neurodevelopmental and multifactorial conditions with cognitive manifestations. The valproic acid (VPA) rat model is a well-validated model that successfully reproduces the behavioral and neuroanatomical alterations of ASD. Previous studies found atypical brain connectivity and metabolic patterns in VPA animals: local glucose hypermetabolism in the prefrontal cortex, with no metabolic changes in the hippocampus.
View Article and Find Full Text PDFElife
September 2025
Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, United States.
The microglial surface protein Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) plays a critical role in mediating brain homeostasis and inflammatory responses in Alzheimer's disease (AD). The soluble form of TREM2 (sTREM2) exhibits neuroprotective effects in AD, though the underlying mechanisms remain elusive. Moreover, differences in ligand binding between TREM2 and sTREM2, which have major implications for their roles in AD pathology, remain unexplained.
View Article and Find Full Text PDFMol Omics
September 2025
Division of Animal Sciences, University of Missouri, 920 East Campus Drive, Columbia, Missouri 65211, USA.
Mice lacking caveolin-1 (), a major protein of the lipid raft of plasma membrane, show deregulated cellular proliferation of the mammary gland and an abnormal fetoplacental communication during pregnancy. This study leverages a multi-omics approach to test the hypothesis that the absence of elicits a coordinated crosstalk of genes among the mammary gland, placenta and fetal brain in pregnant mice. Integrative analysis of metabolomics and transcriptomics data of mammary glands showed that the loss of significantly impacted specific metabolites and metabolic pathways in the pregnant mice.
View Article and Find Full Text PDFJ Chem Theory Comput
September 2025
Department of Materials Science and Engineering, City University of Hong Kong, Kowloon 999077, Hong Kong China.
Coarse-grained (CG) lipid models enable efficient simulations of large-scale membrane events. However, achieving both speed and atomic-level accuracy remains challenging. Graph neural networks (GNNs) trained on all-atom (AA) simulations can serve as CG force fields, which have demonstrated success in CG simulations of proteins.
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