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Opportunities for More Tailored Approaches to Genotoxicity Testing and Carcinogenicity Strategy for Oligonucleotide Therapeutics: Outcome of an Industry Survey.
Nucleic Acid Ther
January 2025
Global Preclinical Safety, AbbVie Inc., North Chicago, Illinois, USA.
The Oligonucleotide Nonclinical Working Group (WG) of the European Federation of Pharmaceutical Industries and Associations conducted an industry survey to understand current practices and regulatory expectations for genotoxicity and carcinogenicity assessment of oligonucleotide therapeutics (ONTs), along with historical genotoxicity testing results. The survey, involving 29 pharmaceutical and biotechnology companies, revealed a consistent absence of genotoxicity across a diverse range of oligonucleotide classes and chemistries, consistent with previous observations. Despite the lack of genotoxicity, companies continue to follow standard testing guidelines, with only limited divergence.
View Article and Find Full Text PDFThe genomes of the most diverse AA genome rice species provide a resource for rice improvement and studies of rice evolution and domestication.
BMC Genomics
January 2025
Queensland Alliance for Agriculture and Food Innovation, University of Queensland, Brisbane, QLD, Australia.
Rice (Oryza sativa) is a staple food crop globally, with origins in wild progenitors within the AA genome group of Oryza species. Oryza rufipogon and Oryza meridionalis are native to tropical Asia and Northern Australia and offer unique genetic reservoirs. Here we explored the relationships of the genomes of these wild rice species with the domesticated rice genome.
View Article and Find Full Text PDFDispersal of influenza virus populations within the respiratory tract shapes their evolutionary potential.
Proc Natl Acad Sci U S A
January 2025
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.
Viral infections are characterized by dispersal from an initial site to secondary locations within the host. How the resultant spatial heterogeneity shapes within-host genetic diversity and viral evolutionary pathways is poorly understood. Here, we show that virus dispersal within and between the nasal cavity and trachea maintains diversity and is therefore conducive to adaptive evolution, whereas dispersal to the lungs gives rise to population heterogeneity.
View Article and Find Full Text PDFAF-FLOW Global Registry Confirms Validity of Electrographic Flow Mapping as a Phenotyping Tool for Atrial Fibrillation.
J Cardiovasc Electrophysiol
January 2025
McGill University Health Centre, Montreal, Canada.
Background: Electrographic flow (EGF) mapping allows for the visualization of global atrial wavefront propagations. One mechanism of initiation and maintenance of atrial fibrillation (AF) is stimulation from EGF-identified focal sources that serve as driver sites of fibrillatory conduction. Electrographic flow consistency (EGFC) further quantifies the concordance of observed wavefront patterns, indicating that a healthier substrate shows more organized wavefront propagation and higher EGFC.
View Article and Find Full Text PDFDivergent roles of mA in orchestrating brown and white adipocyte transcriptomes and systemic metabolism.
Nat Commun
January 2025
Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center; Department of Medicine, BIDMC; Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.
N-methyladenosine (mA) is among the most abundant mRNA modifications, yet its cell-type-specific regulatory roles remain unclear. Here we show that mA methyltransferase-like 14 (METTL14) differentially regulates transcriptome in brown versus white adipose tissue (BAT and WAT), leading to divergent metabolic outcomes. In humans and mice with insulin resistance, METTL14 expression differs significantly from BAT and WAT in the context of its correlation with insulin sensitivity.
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