Anti-SP6 (aa 187-251) polyclonal antibody

Cystic fibrosis (CF) is a monogenetic disease caused mostly by the F508del mutation, a deletion of phenylalanine at position 508 of the CF transmembrane conductance regulator (CFTR) protein, which causes improper localization and functioning of this chloride channel in lung, pancreas, and intestine by affecting the normal fluid homeostasis. In CF the lungs are the most affected organ due to the accumulation of thick mucus, which results into heavy bacterial load and associated chronic inflammation. Therefore, novel state-of-theart therapies are needed to circumvent this problem. To address this, a series of compounds (thiazolidin-4-one-1,3,5-triazines) was tested for the inhibition of NF-kappa B, and compounds SP6 and SP5 showed most significant activity (respectively with relative NF-kB activity: 1.82 +/- 1.87 and 1.96 +/- 1.56). Docking studies of the active compounds in the DNA binding surface of the N-terminal domains of NF-kB were also carried out to identify which structural motifs are vital for activity. These compounds were also tested for antibiofilm activity against P. aeruginosa and S. aureus where they showed MIC ranges from 7.81-125 mg mL(-1). The most active compound - SP6 was further assayed by micro-Ussing chamber experiments to determine its CFTR inhibitory properties, given its structural similarity to CFTR Inh(172). Results suggest that SP6 does not inhibit CFTR alone or in combination with Inh(172).

The gain in fitness during adaptation depends on the supply of beneficial mutations. Despite a good theoretical understanding of how evolution proceeds for a defined set of mutations, there is little understanding of constraints on net fitnesswhether fitness will reach a limit despite ongoing selection and mutation, and if there is a limit, what determines it. Here, the dsDNA bacteriophage SP6, a virus of Salmonella, was adapted to Escherichia coli K-12. From an isolate capable of modest growth on E. coli, four lines were adapted for rapid growth by protocols differing in use of mutagen, propagation method, and duration, but using the same media, temperature, and a continual excess of the novel host. Nucleotide changes underlying those adaptations differed greatly in number and identity, but the four lines achieved similar absolute fitness at the end, an increase of more than 4000-fold phage descendants per hour. Thus, the fitness landscape allows multiple genetic paths to the same approximate fitness limit. The existence and causes of fitness limits have ramifications to genome engineering, vaccine design, and lethal mutagenesis treatments to cure viral infections.