Exploiting differences in heme biosynthesis between bacterial species to screen for novel antimicrobials

The final three steps of heme biogenesis exhibit notable differences between di- and mono-derm bacteria. The former employs the protoporphyrin-dependent (PPD) pathway, while the latter utilizes the more recently uncovered coproporphyrin-dependent (CPD) pathway. In order to devise a rapid screen for potential inhibitors that differentiate the two pathways, the genes associated with the protoporphyrin pathway in an Escherichia coli YFP strain were replaced with those for the CPD pathway from Staphylococcus aureus (SA) through a sliding modular gene replacement recombineering strategy to generate the E. coli strain Sa-CPD-YFP. Potential inhibitors that differentially target the pathways were identified by screening compound libraries against the YFP-producing Sa-CPD-YFP strain in comparison to a CFP-producing E. coli strain. Using a mixed strain assay, inhibitors targeting either the CPD or PPD heme pathways were identified through a decrease in one fluorescent signal but not the other. An initial screen identified both azole and prodigiosin-derived compounds that were shown to specifically target the CPD pathway and which led to the accumulation of coproheme, indicating that the main target of inhibition would appear to be the coproheme decarboxylase (ChdC) enzyme. In silico modeling highlighted that these inhibitors are able to bind within the active site of ChdC

The Experience of Discrimination and Black-White Health Disparities in Medical Care

The current study of Black patients focuses on how discrimination contributes to racial disparities in health. The authors used a longitudinal methodology to study how perceived past discrimination affects reactions to medical interactions and adherence to physician recommendations. In addition, they explored whether these reactions and/or adherence mediate the relationship between discrimination and patients' health. The participants in this study were 156 Black patients of low socioeconomic status at a primary care clinic. Patients completed questionnaires on their current health, past adherence, and perceived past discrimination. Then, they saw a physician and rated their reactions to the visit. Four and 16 weeks later they reported on their adherence to physician recommendations and overall health. Perceived discrimination was significantly and negatively associated with patient health, reactions to the physician, and adherence. Path analyses indicated that adherence mediated the relationship between discrimination and patient health, but patient reactions to the interaction did not

WISE/NEOWISE Preliminary Analysis and Highlights of the 67P/Churyumov-Gerasimenko Near Nucleus Environs

On January 18-19 and June 28-29 of 2010, the Wide-field Infrared Survey Explorer (WISE) spacecraft imaged the Rosetta mission target, comet 67P/Churyumov-Gerasimenko. We present a preliminary analysis of the images, which provide a characterization of the dust environment at heliocentric distances similar to those planned for the initial spacecraft encounter, but on the outbound leg of its orbit rather than the inbound. Broad-band photometry yields low levels of CO2 production at a comet heliocentric distance of 3.32 AU and no detectable production at 4.18 AU. We find that at these heliocentric distances, large dust grains with mean grain diameters on the order of a millimeter or greater dominate the coma and evolve to populate the tail. This is further supported by broad-band photometry centered on the nucleus, which yield an estimated differential dust particle size distribution with a power law relation that is considerably shallower than average. We set a 3-sigma upper limit constraint on the albedo of the large-grain dust at <= 0.12. Our best estimate of the nucleus radius (1.82 +/- 0.20 km) and albedo (0.04 +/- 0.01) are in agreement with measurements previously reported in the literature