The GimA Locus of Extraintestinal Pathogenic E. coli: Does Reductive Evolution Correlate with Habitat and Pathotype?

IbeA (invasion of brain endothelium), which is located on a genomic island termed GimA, is involved in the pathogenesis of several extraintestinal pathogenic E. coli (ExPEC) pathotypes, including newborn meningitic E. coli (NMEC) and avian pathogenic E. coli (APEC). To unravel the phylogeny of GimA and to investigate its island character, the putative insertion locus of GimA was determined via Long Range PCR and DNA-DNA hybridization in 410 E. coli isolates, including APEC, NMEC, uropathogenic (UPEC), septicemia-associated E. coli (SEPEC), and human and animal fecal isolates as well as in 72 strains of the E. coli reference (ECOR) collection. In addition to a complete GimA (∼20.3 kb) and a locus lacking GimA we found a third pattern containing a 342 bp remnant of GimA in this strain collection. The presence of GimA was almost exclusively detected in strains belonging to phylogenetic group B2. In addition, the complete GimA was significantly more frequent in APEC and NMEC strains while the GimA remnant showed a higher association with UPEC strains. A detailed analysis of the ibeA sequences revealed the phylogeny of this gene to be consistent with that obtained by Multi Locus Sequence Typing of the strains. Although common criteria for genomic islands are partially fulfilled, GimA rather seems to be an ancestral part of phylogenetic group B2, and it would therefore be more appropriate to term this genomic region GimA locus instead of genomic island. The existence of two other patterns reflects a genomic rearrangement in a reductive evolution-like manner

Accuracy of accelerated cine MR imaging at 3 Tesla in longitudinal follow-up of cardiac function.

The ability of fast, parallel-imaging-based cine magnetic resonance (MR) to monitor global cardiac function in longitudinal exams at 3 Tesla was evaluated. Seventeen patients with chronic cardiac disease underwent serial cine MR imaging exams (n = 3) at 3 Tesla. Data were acquired in short-axis orientation using cine steady-state free precession (SSFP) with a spatial resolution of 2.5 x 1.9 mm(2) at 45 ms temporal resolution. Multislice imaging (three slices/breath-hold) was performed using TSENSE acceleration (R = 3) and standard single-slice cine (non-TSENSE) was performed at identical locations in consecutive breath-holds. End-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF) and myocardial mass (MM) of both cine approaches were compared for individual time-points as well as for longitudinal comparison. TSENSE-cine did not show significant differences for EDV (2.6 ml; P = 0.79), ESV (2.2 ml; P = 0.81), EF (-0.3%; P = 0.95) and MM (2.4 g; P = 0.72) in comparison with non-TSENSE. Longitudinal ANOVA analysis did not reveal significant differences for any parameter, neither for non-TSENSE data (all P> 0.7) nor for TSENSE data (all P> 0.9). Multifactorial ANOVA showed non-significant differences (all P> 0.7) at comparable data variances. Data acquisition was significantly shortened using TSENSE. Threefold accelerated multislice cine at 3 Tesla allows accurate assessment of volumetric LV data and accurate longitudinal monitoring of global LV function at a substantially shorter overall examination time

Anti‐fibrotic mechanisms of angiotensin AT 2

The angiotensin AT2 -receptor is a main receptor of the protective arm of the renin-angiotensin-system. Understanding of this unconventional G-protein coupled receptor has significantly advanced during the past decade, largely because of the availability of a selective non-peptide AT2 -receptor agonist, which allowed the conduct of a multitude of studies in animal disease models. This article reviews such preclinical studies that in their entirety provide strong evidence for an anti-fibrotic effect mediated by activation of the AT2 -receptor. Prevention of the development of fibrosis by AT2 -receptor stimulation has been demonstrated in lung, heart, blood vessels, kidney, pancreas and skin. In lung, AT2 -receptor stimulation was even able to reverse existing fibrosis. The article further discusses intracellular signalling mechanisms mediating the AT2 -receptor coupled anti-fibrotic effect, including activation of phosphatases and subsequent interference with pro-fibrotic signalling pathways, induction of matrix-metalloproteinases, and hetero-dimerisation with the AT1 -receptor, the TGF-βRII-receptor or the RXFP1-receptor for relaxin. Knowledge of the anti-fibrotic effects of the AT2 -receptor is of particular relevance, because drugs targeting this receptor have entered clinical development for indications involving fibrotic diseases. This article is protected by copyright. All rights reserved.</p