Inhibition of Bacterial Conjugation by Phage M13 and Its Protein g3p: Quantitative Analysis and Model

Conjugation is the main mode of horizontal gene transfer that spreads antibiotic resistance among bacteria. Strategies for inhibiting conjugation may be useful for preserving the effectiveness of antibiotics and preventing the emergence of bacterial strains with multiple resistances. Filamentous bacteriophages were first observed to inhibit conjugation several decades ago. Here we investigate the mechanism of inhibition and find that the primary effect on conjugation is occlusion of the conjugative pilus by phage particles. This interaction is mediated primarily by phage coat protein g3p, and exogenous addition of the soluble fragment of g3p inhibited conjugation at low nanomolar concentrations. Our data are quantitatively consistent with a simple model in which association between the pili and phage particles or g3p prevents transmission of an F plasmid encoding tetracycline resistance. We also observe a decrease in the donor ability of infected cells, which is quantitatively consistent with a reduction in pili elaboration. Since many antibiotic-resistance factors confer susceptibility to phage infection through expression of conjugative pili (the receptor for filamentous phage), these results suggest that phage may be a source of soluble proteins that slow the spread of antibiotic resistance genes

Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry

Background: Polygenic risk scores (PRSs) have been demonstrated to identify women of European, Asian, and Latino ancestry at elevated risk of developing breast cancer (BC). We evaluated the performance of existing PRSs trained in European ancestry populations among women of African ancestry. Methods: We assembled genotype data for women of African ancestry, including 9241 case subjects and 10 193 control subjects. We evaluated associations of 179- and 313-variant PRSs with overall and subtype-specific BC risk. PRS discriminatory accuracy was assessed using area under the receiver operating characteristic curve. We also evaluated a recalibrated PRS, replacing the index variant with variants in each region that better captured risk in women of African ancestry and estimated lifetime absolute risk of BC in African Americans by PRS category. Results: For overall BC, the odds ratio per SD of the 313-variant PRS (PRS313) was 1.27 (95% confidence interval [CI] = 1.23 to 1.31), with an area under the receiver operating characteristic curve of 0.571 (95% CI = 0.562 to 0.579). Compared with women with average risk (40th-60th PRS percentile), women in the top decile of PRS313 had a 1.54-fold increased risk (95% CI = 1.38-fold to 1.72-fold). By age 85 years, the absolute risk of overall BC was 19.6% for African American women in the top 1% of PRS313 and 6.7% for those in the lowest 1%. The recalibrated PRS did not improve BC risk prediction. Conclusion: The PRSs stratify BC risk in women of African ancestry, with attenuated performance compared with that reported in European, Asian, and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry

MoS2 Decorated Carbon Nanofibers as Efficient and Durable Electrocatalyst for Hydrogen Evolution Reaction

Hydrogen is an efficient fuel which can be generated via water splitting, however hydrogen evolution occurs at high overpotential, and efficient hydrogen evolution catalysts are desired to replace state-of-the-art catalysts such as platinum. Here, we report an advanced electrocatalyst that has low overpotential, efficient charge transfers kinetics, low Tafel slope and durable. Carbon nanofibers (CNFs), obtained by carbonizing electrospun fibers, were decorated with MoS2 using a facile hydrothermal method. The imaging of catalyst reveals a flower like morphology that allows for exposure of edge sulfur sites to maximize the HER process. HER activity of MoS2 decorated over CNFs was compared with MoS2 without CNFs and with commercial MoS2. MoS2 grown over CNFs and MoS2-synthesized produced about 374 and 98 times higher current density at −0.30 V (vs. Reversible Hydrogen Electrode, RHE) compared with the MoS2-commercial sample, respectively. MoS2-commercial, MoS2-synthesized and MoS2 grown over CNFs showed a Tafel slope of 165, 79 and 60 mV/decade, capacitance of 0.99, 5.87 and 15.66 mF/cm2, and turnover frequency of 0.013, 0.025 and 0.54 s−1, respectively. The enhanced performance of MoS2-CNFs is due to large electroactive surface area, more exposure of edge sulfur to the electrolyte, and easy charge transfer from MoS2 to the electrode through conducting CNFs