Analysis of a comprehensive dataset of diversity generating retroelements generated by the program DiGReF.

BACKGROUND: Diversity Generating Retroelements (DGRs) are genetic cassettes that can introduce tremendous diversity into a short, defined region of the genome. They achieve hypermutation through replacement of the variable region with a strongly mutated cDNA copy generated by the element-encoded reverse transcriptase. In contrast to "selfish" retroelements such as group II introns and retrotransposons, DGRs impart an advantage to their host by increasing its adaptive potential. DGRs were discovered in a bacteriophage, but since then additional examples have been identified in some bacterial genomes. RESULTS: Here we present the program DiGReF that allowed us to comprehensively screen available databases for DGRs. We identified 155 DGRs which are found in all major classes of bacteria, though exhibiting sporadic distribution across species. Phylogenetic analysis and sequence comparison showed that DGRs move between genomes by associating with various mobile elements such as phages, transposons and plasmids. The DGR cassettes exhibit high flexibility in the arrangement of their components and easily acquire additional paralogous target genes. Surprisingly, the genomic data alone provide new insights into the molecular mechanism of DGRs. Most notably, our data suggest that the template RNA is transcribed separately from the rest of the element. CONCLUSIONS: DiGReF is a valuable tool to detect DGRs in genome data. Its output allows comprehensive analysis of various aspects of DGR biology, thus deepening our understanding of the role DGRs play in prokaryotic genome plasticity, from the global down to the molecular level.

Dental and periodontal status and risk for progression of carotid atherosclerosis: the inflammation and carotid artery risk for atherosclerosis study dental substudy.

BACKGROUND AND PURPOSE: Dental and periodontal disease are potentially involved in the pathogenesis of atherosclerosis. We investigated whether dental and periodontal status is associated with the presence and future progression of carotid stenosis. METHODS: We randomly selected 411 of 1268 participants from the prospective Inflammation and Carotid Artery Risk for Atherosclerosis Study and evaluated dental and periodontal status and oral hygiene at baseline measuring three World Health Organization-validated indices: DMFT (decayed, missing, filled teeth), SLI (Silness-Löe Index), and CPITN (community periodontal index for treatment needs), respectively. The degree of carotid stenosis was measured by duplex ultrasound at baseline and after median 7.5 months (range=6 to 9 months) to identify patients with progressive carotid stenosis. RESULTS: DMFT (P<0.01), SLI (P=0.048), CPITN (P=0.007), and edentulousness (P=0.007) were associated with the baseline degree of carotid stenosis. Atherosclerosis progression was observed in 48 of 411 patients (11.7%). DMFT (adjusted odds ratio [OR]=1.11, 95% CI=1.01 to 1.22, P=0.032) and SLI (adjusted OR=1.77, 95% CI=1.09 to 2.79, P=0.021), but not CPITN (adjusted OR=1.51, 95% CI=0.89 to 2.45, P=0.16) were significant predictors of disease progression, irrespective of traditional cardiovascular risk factors and the baseline degree of stenosis. Edentulous patients had a significantly increased risk for disease progression as compared with patients with teeth (adjusted OR=2.10, 95% CI=1.06 to 4.16, P=0.33). CONCLUSIONS: Dental status, oral hygiene, and particularly tooth loss are associated with the degree of carotid stenosis and predict future progression of the disease.

The low incidence of diversity-generating retroelements in sequenced genomes.

The insertion of a retrotransposable element is usually associated with adverse or, at best, neutral effects on the host. Diversity-generating retroelements (DGRs) are the first elements that seem to offer a direct selective advantage to their phage or prokaryote host by exact replacement of a short, defined region of a host gene with a hypermutated variant. In a previous study, we presented the software DiGReF for identification of DGRs in genome sequences, and compiled the first comprehensive set of diversity-generating retroelements in public databases. We identified 155 elements in more than 6000 prokaryotic and phage genomes, which was a surprisingly low number. In this commentary, we will discuss the low incidence of these elements and speculate about the biological role of bacterial DGRs.

The impact of dental disease on mortality in patients with asymptomatic carotid atherosclerosis.

BACKGROUND: Dental status and oral hygiene are associated with progression of atherosclerosis in patients with carotid stenosis. It remains unclear whether dental disease is a risk factor for mortality in these patients. We evaluated the bearing of dental disease on mortality among patients with asymptomatic carotid atherosclerosis. METHODS: Three World Health Organization-validated indices in 411 patients with asymptomatic carotid atherosclerosis were evaluated, measuring DMFT (decayed, missing, filled teeth) for dental status, CPITN (community periodontal index for treatment needs) for periodontal status and SLI (Silness-Löe Index) for oral hygiene respectively. Patients were prospectively followed for median 6.2 years (IQR 5.8 to 6.6 years) for all-cause mortality. RESULTS: During follow-up, 107 (26%) deaths occurred (74 cardiovascular causes). DMFT and SLI, but not CPITN, showed a significant and gradual association with mortality. For continuous variables, the adjusted hazard ratios (HR) for death were 1.06 (95% CI 1.0 to 1.12; p = 0.04) for DMFT, and 1.43 (95% CI, 1.01 to 2.03; p = 0.04) for SLI respectively. Edentulousness was a significant risk factor for death (adjusted HR 1.99, 95% CI, 1.18 to 3.02; p = 0.008). CONCLUSION: Dental status and oral hygiene were associated with mortality in patients with carotid atherosclerosis regardless of conventional cardiovascular risk factors.