Replication-associated inversions are the dominant form of bacterial chromosome structural variation.

The structural arrangements of bacterial chromosomes vary widely between closely related species and can result in significant phenotypic outcomes. The appearance of large-scale chromosomal inversions that are symmetric relative to markers for the origin of replication (OriC) has been previously observed; however, the overall prevalence of replication-associated structural rearrangements (RASRs) in bacteria and their causal mechanisms are currently unknown. Here, we systematically identify the locations of RASRs in species with multiple complete-sequenced genomes and investigate potential mediating biological mechanisms. We found that 247 of 313 species contained sequences with at least one large (>50 Kb) inversion in their sequence comparisons, and the aggregated inversion distances away from symmetry were normally distributed with a mean of zero. Many inversions that were offset from dnaA were found to be centered on a different marker for the OriC Instances of flanking repeats provide evidence that breaks formed during the replication process could be repaired to opposing positions. We also found a strong relationship between the later stages of replication and the range in distance variation from symmetry.

Complete Genome Sequences of Klebsiella michiganensis and Citrobacter farmeri, KPC-2-Producers Serially Isolated from a Single Patient.

Carbapenemase-producing Enterobacterales, including KPC-2 producers, have become a major clinical problem. During an outbreak in Quebec City, Canada, KPC-2-producing Klebsiella michiganensis and Citrobacter farmeri were isolated from a patient six weeks apart. We determined their complete genome sequences. Both isolates carried nearly identical IncN2 plasmids with blaKPC-2 on a Tn4401b element. Both strains also carried IncP1 plasmids, but that of C. farmeri did not carry a Beta-lactamase gene, whereas that of K. michiganensis carried a second copy of blaKPC-2 on Tn4401b. These results suggest recent plasmid transfer between the two species and a recent transposition event.

Comparison of short-acting versus extended-release nifedipine: Effects on hemodynamics and sympathetic activity in patients with stable coronary artery disease.

We investigated the impact of short-acting and extended release nifedipine on sympathetic activity using radiotracer methodology in patients with stable coronary artery disease in order to more accurately document the response of the sympathetic nervous system to different formulations of this dihydropyridine calcium channel antagonist. Participants were randomized to placebo, short-acting or extended release nifedipine for 7-10 days. On the final day, systemic blood pressure, cardiac filling pressures, cardiac output, plasma norepinephrine (NE) and total body NE spillover were measured at baseline (time 0) and repeated at intervals for 6 hours. There were no differences in baseline measures between groups. Following the morning dose of study medication there were no changes in hemodynamics or sympathetic activity in the placebo group. However, there was a significant fall in blood pressure and a significant increase in total body NE spillover in both nifedipine groups. Importantly, the increase in sympathetic activity in response to short-acting nifedipine began earlier (30 minutes) and was much greater than that observed in the extended release group, which occurred later (270 minutes). These findings confirm that sustained therapy with nifedipine is associated with activation of the sympathetic nervous system which is dependent on the pharmacokinetics of the formulation.