ABSTRACT
Meiotic crossovers can be formed through the interfering pathway, in which one crossover prevents another from forming nearby, or by an independent non-interfering pathway. In Arabidopsis, local sequence polymorphism between homologs can stimulate interfering crossovers in a MSH2-dependent manner. To understand how MSH2 regulates crossovers formed by the two pathways, we combined Arabidopsis mutants that elevate non-interfering crossovers with msh2 mutants. We demonstrate that MSH2 blocks non-interfering crossovers at polymorphic loci, which is the opposite effect to interfering crossovers. We also observe MSH2-independent crossover inhibition at highly polymorphic sites. We measure recombination along the chromosome arms in lines differing in patterns of heterozygosity and observe a MSH2-dependent crossover increase at the boundaries between heterozygous and homozygous regions. Here, we show that MSH2 is a master regulator of meiotic DSB repair in Arabidopsis, with antagonistic effects on interfering and non-interfering crossovers, which shapes the crossover landscape in relation to interhomolog polymorphism.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/genetics , Crossing Over, Genetic , MutS Homolog 2 Protein/genetics , Arabidopsis Proteins/genetics , Polymorphism, Genetic , Meiosis/geneticsABSTRACT
The COVID-19 pandemic provoked a global health crisis and highlighted the need for new therapeutic strategies. In this study, we explore the potential of the molecular consortia of cannabidiol (CBD) and non-steroidal anti-inflammatory drugs (NSAIDs) as novel antiviral dual-target agents against SARS-CoV-2/COVID-19. CBD is a natural compound with a wide range of therapeutic activities, including antiviral and anti-inflammatory properties, while NSAIDs are commonly used to mitigate the symptoms of viral infections. Chemical modifications of CBD with NSAIDs were performed to obtain dual-target agents with enhanced activity against SARS-CoV-2. The synthesised compounds were characterised using spectroscopic techniques. The biological activity of three molecular consortia (CBD-ibuprofen, CBD-ketoprofen, and CBD-naproxen) was evaluated in cell lines transduced with vesicular stomatitis virus-based pseudotypes bearing the SARS-CoV-1 or SARS-CoV-2 spike proteins or infected with influenza virus A/Puerto Rico/8/34. The results showed that some CBD-NSAID molecular consortia have superior antiviral activity against SARS-CoV-1 and SARS-CoV-2, but not against the influenza A virus. This may suggest a potential therapeutic role for these compounds in the treatment of emerging coronavirus infections. Further studies are needed to investigate the efficacy of these compounds in vivo, and their potential use in clinical settings. Our findings provide a promising new approach to combatting current and future viral emergencies.
ABSTRACT
OBJECTIVES: Wastewater-based epidemiology can determine the scale of a mpox epidemic and thus is a promising additional tool that can complete data gathered by the clinical monitoring approach and predict more accurately the development and progress of the current mpox outbreak. METHODS: We collected daily average samples from two wastewater treatment plants (WTPs): Central and Left-Bank, in Poznan, Poland from July to December 2022. The mpox DNA was detected using real-time polymerase chain reaction and compared with the number of hospitalizations. RESULTS: We detected the mpox DNA in the Central WTP in weeks 29, 43, and 47 and the Left-Bank WTP mostly from mid-September till the end of October. A total of 22 patients with mpox were reported by the public health authority from July to December 2022, with the highest number of hospitalized individuals from mid-July to mid-August. The mpox virus detection does not correlate with the number of hospitalizations in Poznan, Poland. CONCLUSION: Our results suggest that the scale of the mpox epidemic is underestimated, and many mpox virus-infected individuals are not identified by the public health authority.
