In research to date, regulation of the pyrimidine biosynthetic pathway at the level of gene expression has not been shown for wild type Pseudomonas aeruginosa. No repression was observed when uracil was added to the growth medium nor was any derepression seen when Pyr(-) auxotrophs were limited for pyrimidines. Here we show that the addition of uracil to Pseudomonas minimal medium influenced the synthesis of pyrimidine enzymes, while starvation of a pyrimidine knockout mutant (pyrD) elicited derepression of the pyrimidine enzymes. Moreover, the inclusion of orotate in the growth medium induced the synthesis of dihydroorotase in both wild type and mutant. These results suggest that the pyrimidine pathway in P. aeruginosa is regulated at the level of enzyme synthesis in a manner similar to a number of other Pseudomonas species.
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http://dx.doi.org/10.1002/jobm.200610248 | DOI Listing |
Clin Transl Med
January 2025
Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China.
RNA pseudouridylation, a dynamic and reversible post-transcriptional modification found in diverse RNA species, is crucial for various biological processes, including tRNA homeostasis, tRNA transport, translation initiation regulation, pre-mRNA splicing, enhancement of mRNA translation, and translational fidelity. Disruption of pseudouridylation impairs cellular homeostasis, contributing to pathological alterations. Recent studies have highlighted its regulatory role in human diseases, particularly in tumourigenesis.
View Article and Find Full Text PDFEur J Neurosci
January 2025
Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology of the Russian Academy of Sciences, Saint Petersburg, Russia.
The serotonergic raphe magnus (RMg) and dorsal raphe (DR) nuclei are crucial pain-regulating structures, which nociceptive activity is shown to be altered in gut pathology, but the underlying neuroplastic changes remain unclear. Considering the importance of 5-HT1A receptors in modulating both pain and raphe neuronal activity, in this study, we aimed to determine whether 5-HT1A-dependent visceral and somatic nociceptive processing within the RMg and DR is modified in postcolitis conditions. In anaesthetised male Wistar rats, healthy control and recovered from TNBS-induced colitis, the microelectrode recordings of RMg and DR neuron responses to noxious colorectal distension (CRD) or tail squeezing (TS) were performed prior and after intravenous administration of 5-HT1A agonist, buspirone.
View Article and Find Full Text PDFMicrob Cell Fact
January 2025
MOE Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, P. R. China.
Background: Hyaluronic acid (HA) is extensively employed in various fields such as medicine, cosmetics, food, etc. The molecular weight (MW) of HA is crucial for its biological functions. Streptococcus zooepidemicus, a prominent HA industrial producer, naturally synthetizes HA with high MW.
View Article and Find Full Text PDFClin Epigenetics
January 2025
School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, 2308, Australia.
Background: Hypomethylating agents (HMA), such as azacytidine (AZA) and decitabine (DAC), are epigenetic therapies used to treat some patients with acute myeloid leukaemia (AML) and myelodysplastic syndrome. HMAs act in a replication-dependent manner to remove DNA methylation from the genome. However, AML cells targeted by HMA therapy are often quiescent within the bone marrow, where oxygen levels are low.
View Article and Find Full Text PDFJ Pharmacokinet Pharmacodyn
January 2025
Department of Clinical Pharmacy and Pharmacy Administration, West China school of Pharmacy, Sichuan University, Chengdu, 610064, China.
Alogliptin is a highly selective inhibitor of dipeptidyl peptidase-4 and primarily excreted as unchanged drug in the urine, and differences in clinical outcomes in renal impairment patients increase the risk of serious adverse reactions. In this study, we developed a comprehensive physiologically-based quantitative systematic pharmacology model of the alogliptin-glucose control system to predict plasma exposure and use glucose as a clinical endpoint to prospectively understand its therapeutic outcomes with varying renal function. Our model incorporates a PBPK model for alogliptin, DPP-4 activity described by receptor occupancy theory, and the crosstalk and feedback loops for GLP-1-GIP-glucagon, insulin, and glucose.
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