Indirect DNA Readout by an H-NS Related Protein: Structure of the DNA Complex of the C-Terminal Domain of Ler

Ler, a member of the H-NS protein family, is the master regulator of the LEE pathogenicity island in virulent Escherichia coli strains. Here, we determined the structure of a complex between the DNA-binding domain of Ler (CT-Ler) and a 15-mer DNA duplex. CT-Ler recognizes a preexisting structural pattern in the DNA minor groove formed by two consecutive regions which are narrower and wider, respectively, compared with standard B-DNA. The compressed region, associated with an AT-tract, is sensed by the side chain of Arg90, whose mutation abolishes the capacity of Ler to bind DNA. The expanded groove allows the approach of the loop in which Arg90 is located. This is the first report of an experimental structure of a DNA complex that includes a protein belonging to the H-NS family. The indirect readout mechanism not only explains the capacity of H-NS and other H-NS family members to modulate the expression of a large number of genes but also the origin of the specificity displayed by Ler. Our results point to a general mechanism by which horizontally acquired genes may be specifically recognized by members of the H-NS family

Performance of experimental approach embankments at Salt Fork river bridges on U.S. 177 (FHWA-97-04) 2195

In an effort to address the bump at the endˆ of the bridge problem, ODOT has undertaken an experimental construction research project to evaluate five different approach embankment construction methods. The research is being conducted at a relocation project in which three new bridges are being constructed to relocate a two-mile section of U.S. 177 north of Stillwater, Oklahoma. Five of the six approach embankments are approximately the same height and the foundation soils are relatively uniform, consisting of fine to medium dense sands. Materials and construction methods used for the five approach embankments in the study include: unclassified borrow placed by contractor's discretion (i.e., equipment)-this serves as the control for the research study; geotextile reinforced approach embankment using a nonwoven geotextile and granular backfill (i.e., concrete sand); controlled low strength material; dynamically compacted granular backfill; and flooded and vibrated granular backfill. During and following construction, all five approach embankments and. bridge abutments were instrumented to evaluate the performance of the approach embankments and interaction with the abutment walls. Specific instruments and the parameters they monitored included: total pressure cells on the back of the abutment walls to monitor lateral earth pressures caused by the approach embankments; amplified liquid settlement gages beneath the approach embankments to monitor settlement; inclinometer casings with telescoping couplings to monitor lateral displacement and settlement within the approach embankment and foundation materials; piezometers to monitor pore water pressures; and surface survey points to monitor total surface movement. In terms of settlement, the flooded and vibrated granular backfill appears to be performing the best. Lateral earth pressure values are closest to the predicted values for the geotextile reinforced backfill. The CLSM is performing well with respect to settlement. The dynamically compacted granular backfill embankment has the highest amount of settlement. The least expensive embankment construction was the control section which had a total cost of $1500. The most expensive was the geotextile reinforced backfill at$25,000. The remaining embankments cost in the range of $14,500 to$16,000.Final Report July 1993-June 1997N

Prognostic association of plasma NT-proBNP levels in patients with microvascular angina - A report from the international cohort study by COVADIS

Backgroud: The aim of this study was to assess the prognostic association of plasma levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) with clinical outcomes of patients with microvascular angina (MVA). Methods: In this international prospective cohort study of MVA by the Coronary Vasomotor Disorders International Study (COVADIS) group, we examined the association between plasma NT-proBNP levels and the incidence of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure or unstable angina. Results: We examined a total of 226 MVA patients (M/F 66/160, 61.9±10.2 [SD] yrs.) with both plasma NT-proBNP levels and echocardiography data available at the time of enrolment. The median level of NT-proBNP level was 94 pg/ml, while mean left ventricular ejection fraction was 69.2±10.9% and E/e’ 10.7±5.2. During follow-up period of a median of 365 days (IQR 365-482), 29 MACEs occurred. Receiver-operating characteristics curve analysis identified plasma NT-proBNP level of 78 pg/ml as the optimal cut-off value. Multivariable logistic regression analysis revealed that plasma NT-proBNP level ≥78 pg/ml significantly correlated with the incidence of MACE (odds ratio (OR) [95% confidence interval (CI)] 3.11[1.14-8.49], P=0.001). Accordingly, Kaplan-Meier survival analysis showed a significantly worse prognosis in the group with NT-proBNP ≥78 (log-rank test, P<0.03). Finally, a significant positive correlation was observed between plasma NT-proBNP levels and E/e’ (R=0.445, P<0.0001). Conclusions: These results indicate that plasma NT-proBNP levels may represent a novel prognostic biomarker for MVA patients