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High-resolution fleezers reveal duplex opening and stepwise assembly by an oligomer of the DEAD-box helicase Ded1p.
Nat Commun
January 2025
Department of Physics and Astronomy, Michigan State University, East Lansing, MI, USA.
DEAD-box RNA-dependent ATPases are ubiquitous in all domains of life where they bind and remodel RNA and RNA-protein complexes. DEAD-box ATPases with helicase activity unwind RNA duplexes by local opening of helical regions without directional movement through the duplexes and some of these enzymes, including Ded1p from Saccharomyces cerevisiae, oligomerize to effectively unwind RNA duplexes. Whether and how DEAD-box helicases coordinate oligomerization and unwinding is not known and it is unclear how many base pairs are actively opened.
View Article and Find Full Text PDFMetabolic profiles of cutaneous lupus have abnormalities in the nicotinamide adenine dinucleotide pathway.
Lupus Sci Med
January 2025
Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
Objective: Metabolic reprogramming plays a critical role in modulating the innate and adaptive immune response, but its role in cutaneous autoimmune diseases, such as cutaneous lupus erythematosus (CLE), is less well studied. An improved understanding of the metabolic pathways dysregulated in CLE may lead to novel treatment options, biomarkers and insights into disease pathogenesis. The objective was to compare metabolomic profiles in the skin and sera of CLE and control patients using liquid chromatography-mass spectrometry (LC-MS).
View Article and Find Full Text PDFPurine but Not Pyrimidine De Novo Nucleotide Biosynthesis Inhibitors Strongly Enhance the Antiviral Effect of Corresponding Nucleobases Against Dengue Virus.
Molecules
January 2025
Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
Every year, dengue virus affects hundreds of millions of individuals worldwide. To date, there is no specific medication to treat dengue virus infections. Nucleobases, the base of a nucleoside without ribose, are understudied as potential treatments for viral infections.
View Article and Find Full Text PDFThe Pentose Phosphate Pathway: From Mechanisms to Implications for Gastrointestinal Cancers.
Int J Mol Sci
January 2025
Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
The pentose phosphate pathway (PPP), traditionally recognized for its role in generating nicotinamide adenine dinucleotide phosphate (NADPH) and ribose-5-phosphate (R5P), has emerged as a critical metabolic hub with involvements in various gastrointestinal (GI) cancers. The PPP plays crucial roles in the initiation, development, and tumor microenvironment (TME) of GI cancers by modulating redox homeostasis and providing precursors for nucleotide biosynthesis. Targeting PPP enzymes and their regulatory axis has been a potential strategy in anti-GI cancer therapies.
View Article and Find Full Text PDFVX-770, C-A1, and Increased Intracellular cAMP Have Distinct Acute Impacts upon CFTR Activity.
Int J Mol Sci
January 2025
Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA.
The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel that is dysfunctional in individuals with cystic fibrosis (CF). The permeability of CFTR can be experimentally manipulated though different mechanisms, including activation via inducing the phosphorylation of residues in the regulatory domain as well as altering the gating/open probability of the channel. Phosphorylation/activation of the channel is achieved by exposure to compounds that increase intracellular cAMP, with forskolin and IBMX commonly used for this purpose.
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