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is a member of the vaginal and gastrointestinal human microbiota. Here we determined the complete genome sequence of the probiotic strain M247 combining Nanopore and Illumina technologies. The M247 genome is organized in one circular chromosome of 2 336 109 bp, with a GC content of 37.04 % and 2303 ORFs, of which 1962 could be annotated. Analysis of the M247 mobilome, which accounts for 14 % of the whole genome, revealed the presence of: (i) Tn, a novel 14 105 bp long integrative and mobilizable element (IME) containing 16 ORFs; (ii) ΦM247, a novel 42 510 bp long siphovirus prophage containing 52 ORFs; (iii) three clustered regularly interspaced short palindromic repeats (CRISPRs); and (iv) 226 insertion sequences (ISs) belonging to 14 different families. Tn has a modular organization including a mobilization module encoding FtsK homologous proteins and a relaxase, an integration/excision module coding for an integrase and an excisionase, and an adaptation module coding for a class I bacteriocin and homologous to the listeriolysin S () locus of . Genome-wide homology search analysis showed the presence of Tn-like elements in 12 out of 23 . complete public genomes. Mobilization and integration/excision modules are essentially conserved, while the adaptation module is variable since it is the target site for the integration of different ISs. Prophage ΦM247 contains genes for phage structural proteins, DNA replication and packaging, lysogenic and lytic cycles. ΦM247-like prophages are present in seven . complete genomes, with sequence variability mainly due to the integration of ISs. PCR and sequencing showed that the Tn IME excises from the M247 chromosome producing a circular form at a concentration of 4.32×10 copies per chromosome, and reconstitution of the Tn chromosomal target site occurred at 6.65×10 copies per chromosome. The ΦM247 prophage produces an excised form and a reconstituted target site at a level of 3.90×10 and 2.48×10 copies per chromosome, respectively. This study identified two novel genetic elements in . Tn represents the first example of an IME carrying a biosynthetic gene cluster for a class I bacteriocin in .
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http://dx.doi.org/10.1099/mgen.0.001150 | DOI Listing |
Adv Ther
September 2025
Bristol Myers Squibb, Princeton, NJ, 08540, USA.
Background And Objectives: Deucravacitinib, a first-in-class, oral, selective, allosteric tyrosine kinase 2 inhibitor, demonstrated efficacy across the primary endpoint and all key secondary endpoints in the phase 2 PAISLEY SLE trial in patients with active systemic lupus erythematosus (SLE). Here, we describe 2 phase 3 trials [POETYK SLE-1 (NCT05617677), POETYK SLE-2 (NCT05620407)] which will assess the efficacy and safety of deucravacitinib in patients with active SLE. These phase 3 trials have been designed to replicate the successful elements of the phase 2 trial, including its glucocorticoid-tapering strategy and disease activity adjudication.
View Article and Find Full Text PDFJ Cardiovasc Transl Res
September 2025
Department of Cardiology, Bei'an Hospital, Beidahuang Group, Heihe, 164000, Heilongjiang Province, China.
Myocardial ischemia/reperfusion injury (MIRI) worsens ischemic damage, with ferroptosis as a key mediator of this iron-dependent cell death. Lactylation, a novel epigenetic modification, remains poorly understood in MIRI-associated ferroptosis. This study aimed to elucidate the mechanistic link between lactylation and ferroptosis in MIRI.
View Article and Find Full Text PDFJ Med Chem
September 2025
Repare Therapeutics, 7171 Frederick-Banting, Building 2, H4S 1Z9 Montréal, Québec, Canada.
DNA polymerase theta (Polθ) plays a critical role in repairing DNA double-strand breaks through microhomology-mediated end joining (MMEJ) and has emerged as a key synthetic lethal drug target in cancers with homologous recombination (HR) deficiencies. Its inhibition has shown a strong potential to synergize with PARP inhibitors, particularly in tumors with deleterious or mutations. Here, we describe the discovery and preclinical development of RP-2119, a selective, potent, and bioavailable Polθ ATPase inhibitor.
View Article and Find Full Text PDFJ Chem Phys
September 2025
Department of Chemistry, Princeton University, Princeton, New Jersey 08544, USA.
We present a self-consistent algorithm for optimal control simulations of many-body quantum systems. The algorithm features a two-step synergism that combines discrete real-time machine learning (DRTL) with Quantum Optimal Control Theory (QOCT) using the time-dependent Schrödinger equation. Specifically, in step (1), DRTL is employed to identify a compact working space (i.
View Article and Find Full Text PDFJ Bacteriol
September 2025
Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Essential genes are interesting in their own right and as potential antibiotic targets. To date, only one report has identified essential genes on a genome-wide scale in , a problematic pathogen for which treatment options are limited. That foundational study used large-scale transposon mutagenesis to identify 404 protein-encoding genes as likely to be essential for vegetative growth of the epidemic strain R20291.
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