Much of the human genome is transcribed into RNAs, many of which contain structural elements that are important for their function. Such RNA molecules-including those that are structured and well-folded-are conformationally heterogeneous and flexible, which is a prerequisite for function, but this limits the applicability of methods such as NMR, crystallography and cryo-electron microscopy for structure elucidation. Moreover, owing to the lack of a large RNA structure database, and no clear correlation between sequence and structure, approaches such as AlphaFold for protein structure prediction do not apply to RNA. Therefore, determining the structures of heterogeneous RNAs remains an unmet challenge. Here we report holistic RNA structure determination method using atomic force microscopy, unsupervised machine learning and deep neural networks (HORNET), a novel method for determining three-dimensional topological structures of RNA using atomic force microscopy images of individual molecules in solution. Owing to the high signal-to-noise ratio of atomic force microscopy, this method is ideal for capturing structures of large RNA molecules in distinct conformations. In addition to six benchmark cases, we demonstrate the utility of HORNET by determining multiple heterogeneous structures of RNase P RNA and the HIV-1 Rev response element (RRE) RNA. Thus, our method addresses one of the major challenges in determining heterogeneous structures of large and flexible RNA molecules, and contributes to the fundamental understanding of RNA structural biology.
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http://dx.doi.org/10.1038/s41586-024-07559-x | DOI Listing |
Int J Pharm
December 2024
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine.
Aim: This study focuses on the design and investigation a transethosomal formulation for enhanced topical delivery and improved analgesic activity of caryophyllene oxide. In addition, this work explores new potential mechanisms of analgesic activity of the active compound including alpha-amino-3-hydroxy-5-methyl-4-isooxazole-propionic acid (AMPA) and Cyclooxygenase 2 (COX-2).
Methods: The transethosomal system containing various caryophyllene concentrations was prepared.
Int J Biol Macromol
December 2024
Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin 300457, PR China; Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, PR China; College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address:
Soluble cytotoxic oligomers produced during the fibrillation of both α-synuclein (αS) and amyloid-β protein (Aβ) are key pathogenic factors in Parkinson's disease (PD) and Alzheimer's disease (AD). Reducing toxic oligomers by regulating the aggregation process of αS and Aβ is an important strategy for the treatment of PD and AD. Herein, tetrahydrofolic acid (THF) is found to accelerate amyloid fibrillization, decreases cytotoxic oligomers and suppresses their toxicity.
View Article and Find Full Text PDFWater Res
December 2024
School of Architecture, Civil and Environmental Engineering (ENAC), École Polytechnique Fedérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland; Eawag, Swiss Federal Institute of Aquatic Science and Technology (Eawag), CH-8600 Dübendorf, Switzerland. Electronic address:
Bacterial spores pose significant risks to human health, yet the inactivation of spores is challenging due to their unique structures and chemical compositions. This study investigated the synergistic effect between surfactants and chlorine on the inactivation kinetics of Bacillus subtilis spores. Two surfactants, cocamidopropyl betaine (CAPB) and cetyltrimethylammonium chloride (CTMA) were selected to investigate chlorine disinfection in absence and presence of surfactants.
View Article and Find Full Text PDFACS Appl Mater Interfaces
December 2024
Department of Materials and Environmental Chemistry, Stockholm University, Svante Arrhenius väg 16C, 10691 Stockholm, Sweden.
There is a growing demand for biobased functional materials that can ensure targeted pesticide delivery and minimize active ingredient loss in the agricultural sector. In this work, we demonstrated the use of esterified lignin nanoparticles (ELNPs) as carriers and controlled-release agents of hydrophobic compounds. Curcumin was selected as a hydrophobic model compound and was incorporated during ELNP fabrication with entrapment efficiencies exceeding 95%.
View Article and Find Full Text PDFJ Mol Model
December 2024
School of Mechanical and Electrical Engineering, Lanzhou University of Technology, Lanzhou, 730050, China.
Context: This study employs molecular dynamics simulations to investigate the nanoscale tribological behavior of a single transverse grain boundary in a nickel-based polycrystalline alloy. A series of simulations were conducted using a repetitive rotational friction method to explore the mechanisms by which different grain boundary positions influence variations in wear depth, friction force, friction coefficient, dislocation, stress, and internal damage during repeated friction processes. The results reveal that the grain boundary structure enhances the strength of the nanoscale nickel-based polycrystalline alloy.
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