E-64 [trans-epoxysuccinyl-1-leucyl-amido (4-guanido) butane] is teratogenic, inducing a spec-trum of malformations in vivo and producing similar effects in vitro. Numerous studies support the concept that E-64-induced malformations result from embryonic nutritionaldeficiency, without affecting the maternal nutritional status. This has provided a useful model with which to investigate the nutritional requirements of the early embryo, as well as the role of various nutrients in the etiology of congenital defects. In the current investigation, we examined effects of L-methionine on E-64-induced embryotoxicity in vitro. For these experiments, we cultured rat embryos 9.5 days postconception (p.c.) for 48 hours with E-64 and/or L-methionine. We found that the addition of L-methionine to E-64-exposed cultures reduced optic abnormality and increased embryo protein. These results suggest that embryopathy largely results from a deficiency of L-methionine although E-64 limits the supply of all amino acids to the embryo. Furthermore, although endocytosis and degradation of proteins by the visceral yolk sac (VYS) supply most amino acids to the embryo, free amino acids may be compensatory when this source is reduced. These results support those of previous investigations that suggest L-methionine is a limiting nutrient for embryonic development.
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http://dx.doi.org/10.1111/j.1741-4520.2003.tb01014.x | DOI Listing |
Sci Rep
December 2024
Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, is widely used to treat heart failure. Despite its efficacy, sacubitril/valsartan inevitably causes adverse events such as hypotension, renal dysfunction, hyperkalemia, and angioedema. Sacubitril/valsartan-associated ototoxicity is often underreported in clinical studies and real-world settings.
View Article and Find Full Text PDFNPJ Biofilms Microbiomes
December 2024
Costerton Biofilm Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, 2200, Denmark.
The evolution of antimicrobial resistance (AMR) in biofilms, driven by mechanisms like oxidative stress, is a major challenge. This study investigates whether antioxidants (AOs) such as N-acetyl-cysteine (NAC) and Edaravone (ED) can reduce AMR in Pseudomonas aeruginosa biofilms exposed to sub-inhibitory concentrations of ciprofloxacin (CIP). In vitro experimental evolution studies were conducted using flow cells and glass beads biofilm models.
View Article and Find Full Text PDFNat Commun
December 2024
State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
The faithful charging of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (AARSs) determines the fidelity of protein translation. Isoleucyl-tRNA synthetase (IleRS) distinguishes tRNA from tRNA solely based on the nucleotide at wobble position (N34), and a single substitution at N34 could exchange the aminoacylation specificity between two tRNAs. Here, we report the structural and biochemical mechanism of N34 recognition-based tRNA discrimination by Saccharomyces cerevisiae IleRS (ScIleRS).
View Article and Find Full Text PDFNat Commun
December 2024
Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
The mechanism(s) underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) is unknown. Herein we observe elevation in circulating phenylacetylglutamine (PAGln), a known CVD-associated GMM, in individuals living with alcohol use disorder. In a male murine binge-on-chronic alcohol model, we confirm gut microbial reorganization, elevation in PAGln levels, and the presence of cardiovascular pathophysiology.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Chemistry, Ulsan National Institute of Science and Technology, Ulsan, 44919, Republic of Korea.
Oxidative modifications can disrupt protein folds and functions, and are strongly associated with human aging and diseases. Conventional oxidation pathways typically involve the free diffusion of reactive oxygen species (ROS), which primarily attack the protein surface. Yet, it remains unclear whether and how internal protein folds capable of trapping oxygen (O) contribute to oxidative damage.
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