A computational approach for identifying pathogenicity islands in prokaryotic genomes

BACKGROUND: Pathogenicity islands (PAIs), distinct genomic segments of pathogens encoding virulence factors, represent a subgroup of genomic islands (GIs) that have been acquired by horizontal gene transfer event. Up to now, computational approaches for identifying PAIs have been focused on the detection of genomic regions which only differ from the rest of the genome in their base composition and codon usage. These approaches often lead to the identification of genomic islands, rather than PAIs. RESULTS: We present a computational method for detecting potential PAIs in complete prokaryotic genomes by combining sequence similarities and abnormalities in genomic composition. We first collected 207 GenBank accessions containing either part or all of the reported PAI loci. In sequenced genomes, strips of PAI-homologs were defined based on the proximity of the homologs of genes in the same PAI accession. An algorithm reminiscent of sequence-assembly procedure was then devised to merge overlapping or adjacent genomic strips into a large genomic region. Among the defined genomic regions, PAI-like regions were identified by the presence of homolog(s) of virulence genes. Also, GIs were postulated by calculating G+C content anomalies and codon usage bias. Of 148 prokaryotic genomes examined, 23 pathogenic and 6 non-pathogenic bacteria contained 77 candidate PAIs that partly or entirely overlap GIs. CONCLUSION: Supporting the validity of our method, included in the list of candidate PAIs were thirty four PAIs previously identified from genome sequencing papers. Furthermore, in some instances, our method was able to detect entire PAIs for those only partial sequences are available. Our method was proven to be an efficient method for demarcating the potential PAIs in our study. Also, the function(s) and origin(s) of a candidate PAI can be inferred by investigating the PAI queries comprising it. Identification and analysis of potential PAIs in prokaryotic genomes will broaden our knowledge on the structure and properties of PAIs and the evolution of bacterial pathogenesis

Towards pathogenomics: a web-based resource for pathogenicity islands

Pathogenicity islands (PAIs) are genetic elements whose products are essential to the process of disease development. They have been horizontally (laterally) transferred from other microbes and are important in evolution of pathogenesis. In this study, a comprehensive database and search engines specialized for PAIs were established. The pathogenicity island database (PAIDB) is a comprehensive relational database of all the reported PAIs and potential PAI regions which were predicted by a method that combines feature-based analysis and similarity-based analysis. Also, using the PAI Finder search application, a multi-sequence query can be analyzed onsite for the presence of potential PAIs. As of April 2006, PAIDB contains 112 types of PAIs and 889 GenBank accessions containing either partial or all PAI loci previously reported in the literature, which are present in 497 strains of pathogenic bacteria. The database also offers 310 candidate PAIs predicted from 118 sequenced prokaryotic genomes. With the increasing number of prokaryotic genomes without functional inference and sequenced genetic regions of suspected involvement in diseases, this web-based, user-friendly resource has the potential to be of significant use in pathogenomics. PAIDB is freely accessible at

The Differential Effects of Acute Right- vs. Left-Sided Vestibular Deafferentation on Spatial Cognition in Unilateral Labyrinthectomized Mice

This study aimed to investigate the disparity in locomotor and spatial memory deficits caused by left- or right-sided unilateral vestibular deafferentation (UVD) using a mouse model of unilateral labyrinthectomy (UL) and to examine the effects of galvanic vestibular stimulation (GVS) on the deficits over 14 days. Five experimental groups were established: the left-sided and right-sided UL (Lt.-UL and Rt.-UL) groups, left-sided and right-sided UL with bipolar GVS with the cathode on the lesion side (Lt.-GVS and Rt.-GVS) groups, and a control group with sham surgery. We assessed the locomotor and cognitive-behavioral functions using the open field (OF), Y maze, and Morris water maze (MWM) tests before (baseline) and 3, 7, and 14 days after surgical UL in each group. On postoperative day (POD) 3, locomotion and spatial working memory were more impaired in the Lt.-UL group compared with the Rt.-UL group (p < 0.01, Tamhane test). On POD 7, there was a substantial difference between the groups; the locomotion and spatial navigation of the Lt.-UL group recovered significantly more slowly compared with those of the Rt.-UL group. Although the differences in the short-term spatial cognition and motor coordination were resolved by POD 14, the long-term spatial navigation deficits assessed by the MWM were significantly worse in the Lt.-UL group compared with the Rt.-UL group. GVS intervention accelerated the vestibular compensation in both the Lt.-GVS and Rt.-GVS groups in terms of improvement of locomotion and spatial cognition. The current data imply that right- and left-sided UVD impair spatial cognition and locomotion differently and result in different compensatory patterns. Sequential bipolar GVS when the cathode (stimulating) was assigned to the lesion side accelerated recovery for UVD-induced spatial cognition, which may have implications for managing the patients with spatial cognitive impairment, especially that induced by unilateral peripheral vestibular damage on the dominant side

Complexity of Atherosclerotic Coronary Artery Disease and Long-Term Outcomes in Patients With Unprotected Left Main Disease Treated With Drug-Eluting Stents or Coronary Artery Bypass Grafting

ObjectivesThe aim of this study was to compare treatment effects of drug-eluting stents (DES) or coronary artery bypass grafting (CABG) for left main coronary artery (LMCA) disease according to the complexity of atherosclerotic disease burden.BackgroundLimited information is available on the relationships between the extent of coronary atherosclerosis and very long-term outcomes of surgical or percutaneous LMCA revascularization.MethodsA total of 1,146 patients with unprotected LMCA disease who received DES (n = 645) or underwent CABG (n = 501) were evaluated. The extent of atherosclerotic disease burden was measured using the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score; a low-risk score was defined as ≤22, an intermediate-risk score as 23 to 32, and a high-risk score as ≥33.ResultsAfter multivariate adjustment with the inverse-probability-of-treatment weighting method, the 5-year risks for death (6.1% for DES vs. 16.2% for CABG; hazard ratio [HR]: 0.52; 95% confidence interval [CI]: 0.21 to 1.28; p = 0.15) and the composite of death, Q-wave myocardial infarction, or stroke (6.4% vs. 16.2%; HR: 0.54; 95% CI: 0.22 to 1.34; p = 0.18) favored DES in patients with low-risk SYNTAX scores; in contrast, the 5-year risks for death (26.9% vs. 17.8%; HR: 1.46; 95% CI: 0.92 to 2.30; p = 0.11) and the composite outcome (27.6% vs. 19.5%; HR: 1.36; 95% CI: 0.87 to 2.12; p = 0.18) favored CABG in patients with high-risk SYNTAX scores (interaction p = 0.047 for death, interaction p = 0.08 for composite outcome). Patients undergoing CABG consistently had lower rates of target vessel revascularization.ConclusionsAccording to the complexity of concomitant coronary disease, there were differential treatment effects on long-term mortality in patients with unprotected LMCA disease who received DES or underwent CABG

bending resistance and cyclic fatigue resistance of waveone gold reciproc blue and hyflex edm instruments

Abstract Background/purpose Several single-file systems manufactured using different heat treatment and operated by different kinematics have been released. This study compared the bending resistance and cyclic fatigue resistance of three NiTi files, and examined their phase-transformation behavior. Materials and methods WaveOne Gold Primary (WOG), Reciproc Blue R25 (RPB), and HyFlex EDM OneFile (HDM) were tested (N = 40/instrument). A vertical load was applied to a point 3 mm from the tip, and the stress was measured until a displacement of 3 mm. Tests were conducted at either room temperature (RT: 22 °C) or body temperature (BT: 37 °C) (n = 10). Cyclic fatigue resistance tests were performed in an artificial canal, which had a curvature angle of 40° and a 5-mm radius. Tests were conducted at either RT or BT (n = 10). Instruments were operated according to the manufacturers' instructions. Test results were analyzed using the Kruskal–Wallis and the Mann–Whitney tests. Additional three instruments of each brand were subjected to differential scanning calorimetry (DSC). Results At RT the bending resistance of three files were not significantly different. However, at BT the bending resistance of RPB was highest, followed by WOG, and HDM (P  Conclusion HDM presented superior flexibility and cyclic fatigue resistance at BT

Direct cell-to-cell transfer in stressed tumor microenvironment aggravates tumorigenic or metastatic potential in pancreatic cancer.

Pancreatic cancer exhibits a characteristic tumor microenvironment (TME) due to enhanced fibrosis and hypoxia and is particularly resistant to conventional chemotherapy. However, the molecular mechanisms underlying TME-associated treatment resistance in pancreatic cancer are not fully understood. Here, we developed an in vitro TME mimic system comprising pancreatic cancer cells, fibroblasts and immune cells, and a stress condition, including hypoxia and gemcitabine. Cells with high viability under stress showed evidence of increased direct cell-to-cell transfer of biomolecules. The resulting derivative cells (CD4

Beneficial Effect of Efonidipine, an L- and T-Type Dual Calcium Channel Blocker, on Heart Rate and Blood Pressure in Patients With Mild-to-Moderate Essential Hypertension

Background and Objectives: Efonidipine hydrochloride, an L- and T-type dual calcium channel blocker, is suggested to have a heart rate (HR)-slowing action in addition to a blood pressure (BP)-lowering effect. The aim of this study was to determine the effect of efonidipine on HR and BP in patients with mild-to-moderate hypertension. Subjects and Methods: In a multi-center, prospective, open-labeled, single-armed study, we enrolled 53 patients who had mild-to-moderate hypertension {sitting diastolic BP (SiDBP) 90-110 mmHg}. After a 2-week washout, eligible patients were treated with efonidipine (40 mg once daily for 12 weeks). The primary end point was the change in HR from baseline to week 12. The secondary end-point included the change in trough sitting BP and 24-hour mean BP between baseline and week 12. Laboratory and clinical adverse events were monitored at each study visit (4, 8, and 12 weeks). Results: Fifty-two patients were included in the intention-to-treat analysis. After 12 weeks of treatment with efonidipine, the resting HR decreased significantly from baseline to week 12 (from 81.5??5.3 to 71.8??9.9 beats/minute (difference, -9.9??9.0 beats/minute), p<0.0001}. The trough BP {sitting systolic blood pressure (SiSBP) and SiDBP} and 24-hour mean BP also decreased significantly (SiSBP: from 144.6??8.2 to 132.9??13.5 mmHg, p<0.0001; SiDBP: from 96.9??5.4 to 88.3??8.6 mmHg, p<0.0001, 24-hour mean systolic BP: from 140.4??13.5 to 133.8??11.6 mmHg, p<0.0001; 24-hour mean diastolic BP: from 91.7??8.7 to 87.5??9.5 mmHg, p<0.0001). Conclusion: Efonidipine was effective in controlling both HR and BP in patients with mild-to-moderate hypertension. Copyright ?? 2010 The Korean Society of Cardiology