Mobility of the SecA 2-helix-finger is not essential for polypeptide translocation via the SecYEG complex

The bacterial ATPase SecA and protein channel complex SecYEG form the core of an essential protein translocation machinery. The nature of the conformational changes induced by each stage of the hydrolytic cycle of ATP and how they are coupled to protein translocation are not well understood. The structure of the SecA–SecYEG complex revealed a 2-helix-finger (2HF) of SecA in an ideal position to contact the substrate protein and push it through the membrane. Surprisingly, immobilization of this finger at the edge of the protein channel had no effect on translocation, whereas its imposition inside the channel blocked transport. This analysis resolves the stoichiometry of the active complex, demonstrating that after the initiation process translocation requires only one copy each of SecA and SecYEG. The results also have important implications on the mechanism of energy transduction and the power stroke driving transport. Evidently, the 2HF is not a highly mobile transducing element of polypeptide translocation

Understanding the national performance of flood forecasting models to guide incident management and investment

The preparation of routine flood guidance statements and formulation of incident management strategies requires national operating agencies to have a firm understanding of the performance of flood forecasting models. Studies of flood forecasting model performance are commonly evaluated on a groupedcatchment or local basis and can lack the analytical consistency required for integration into coherent national assessments. Here, the first nationally consistent analysis of flood forecasting model performance across England and Wales is presented. Application of the assessment framework, accounting for regional and model-type differences, yields a national overview of relative forecasting capability for models in current operational use. To achieve extensive site coverage, information from many existing local performance studies are pooled into a single structure for analysis under a national framework. The performance information spanning a variety of local models is also compared against the area-wide national G2G (Grid-to-Grid) distributed model. An integrated national assessment gives an evidence base of model performance useful for guiding strategic planning and investment in flood forecasting models. A concise single-page Performance Summary has been created for each site model that contains performance statistics, forecast hydrographs and catchment properties to aid operational use. A prototype web portal has been developed to make information on forecasting model performance more accessible and understandable for end-users

The dynamic action of SecA during the initiation of protein translocation

Biotechnology and Biological Sciences Research Council (BBSRC) [a doctoral training grant Ph.D. studentship to S.W. and project grant number BB/I008675/1] and the Wellcome Trust [project grant number 084452]

Temperature dependence of the zero-phonon linewidth in quantum dots: An effect of the fluctuating environment

We report systematic measurements on the broadening of the emission spectrum of single quantum dots as a function of temperature and incident power. Spectral diffusion effects in the motional narrowing regime provide a quantitative interpretation of our experimental results. We show that, at low incident power, the thermal activation of spectral diffusion results in a Lorentzian zero-phonon line with a width that increases linearly with temperature. Our study provides a unified interpretation to the widely debated issue of the dispersion of the data on the temperature dependence of this zero-phonon linewidth. Our explanation is based on an original model where acoustic phonons interact with carriers outside the quantum dot

Structural and Functional Analysis of Cell Wall-Anchored PolypeptideAdhesin BspA in <i>Streptococcus agalactiae</i>

Streptococcus agalactiae (group B Streptococcus, GBS) is the predominant cause of early-onset infectious disease in neonates and is responsible for life-threatening infections in elderly and immunocompromised individuals. Clinical manifestations of GBS infection include sepsis, pneumonia, and meningitis. Here, we describe BspA, a deviant antigen I/II family polypeptide that confers adhesive properties linked to pathogenesis in GBS. Heterologous expression of BspA on the surface of the non-adherent bacterium Lactococcus lactis confers adherence to scavenger receptor gp340, human vaginal epithelium, and to the fungus Candida albicans. Complementary crystallographic and biophysical characterization of BspA reveal a novel β-sandwich adhesion domain and unique asparagine-dependent super-helical stalk. Collectively, these findings establish a new bacterial adhesin structure that has in effect been hijacked by a pathogenic Streptococcus species to provide competitive advantage in human mucosal infections

An optical-IR jet in 3C133

We report the discovery of a new optical-IR synchrotron jet in the radio galaxy 3C133 from our HST/NICMOS snapshot survey. The jet and eastern hotspot are well resolved, and visible at both optical and IR wavelengths. The IR jet follows the morphology of the inner part of the radio jet, with three distinct knots identified with features in the radio. The radio-IR SED's of the knots are examined, along with those of two more distant hotspots at the eastern extreme of the radio feature. The detected emission appears to be synchrotron, with peaks in the NIR for all except one case, which exhibits a power-law spectrum throughout.Comment: ApJ accepted. 14 pages, 6 figure

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations