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Palmitate potentiates the SMAD3-PAI-1 pathway by reducing nuclear GDF15 levels.
Cell Mol Life Sci
January 2025
Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Unitat de Farmacologia, Universitat de Barcelona, Av. Joan XXIII 27-31, 08028, Barcelona, Spain.
Nuclear growth differentiation factor 15 (GDF15) reduces the binding of the mothers' against decapentaplegic homolog (SMAD) complex to its DNA-binding elements. However, the stimuli that control this process are unknown. Here, we examined whether saturated fatty acids (FA), particularly palmitate, regulate nuclear GDF15 levels and the activation of the SMAD3 pathway in human skeletal myotubes and mouse skeletal muscle, where most insulin-stimulated glucose use occurs in the whole organism.
View Article and Find Full Text PDFDefective homologous recombination and genomic instability predict increased responsiveness to carbon ion radiotherapy in pancreatic cancer.
NPJ Precis Oncol
January 2025
Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Pancreatic ductal adenocarcinoma (PDAC) is notably resistant to conventional chemotherapy and radiation treatment. However, clinical trials indicate that carbon ion radiotherapy (CIRT) with concurrent gemcitabine is effective for unresectable locally advanced PDAC. This study aimed to identify patient characteristics predictive of CIRT response.
View Article and Find Full Text PDFDecoding the mA epitranscriptomic landscape for biotechnological applications using a direct RNA sequencing approach.
Nat Commun
January 2025
National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, National Engineering Research Center for New Drug and Druggability (cultivation), Guangdong Province Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
Epitranscriptomic modifications, particularly N6-methyladenosine (mA), are crucial regulators of gene expression, influencing processes such as RNA stability, splicing, and translation. Traditional computational methods for detecting mA from Nanopore direct RNA sequencing (DRS) data are constrained by their reliance on experimentally validated labels, often resulting in the underestimation of modification sites. Here, we introduce pum6a, an innovative attention-based framework that integrates positive and unlabeled multi-instance learning (MIL) to address the challenges of incomplete labeling and missing read-level annotations.
View Article and Find Full Text PDFStructural basis for metal ion transport by the human SLC11 proteins DMT1 and NRAMP1.
Nat Commun
January 2025
Department of Biochemistry, University of Zurich, Zurich, Switzerland.
Iron and manganese are essential nutrients whose transport across membranes is catalyzed by members of the SLC11 family. In humans, this protein family contains two paralogs, the ubiquitously expressed DMT1, which is involved in the uptake and distribution of Fe and Mn, and NRAMP1, which participates in the resistance against infections and nutrient recycling. Despite previous studies contributing to our mechanistic understanding of the family, the structures of human SLC11 proteins and their relationship to functional properties have remained elusive.
View Article and Find Full Text PDFA sensitive immunoassay for the rapid analysis of fluopicolide.
Talanta
January 2025
Institute of Agrochemistry and Food Technology, Spanish Council for Scientific Research (IATA-CSIC), Av. Agustí Escardino 7, Paterna, 46980, Valencia, Spain. Electronic address:
The analysis of chemical xenobiotics in human, food, and environmental samples has become a global priority. Consequently, both public and private laboratories require rapid, cost-effective analytical methods for quality and safety control. Fluopicolide, a fungicide used to combat plant diseases, poses potential toxicological risks to humans and animals.
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