Comparative analyses imply that the enigmatic sigma factor 54 is a central controller of the bacterial exterior

Contains fulltext : 95738.pdf (publisher's version ) (Open Access)BACKGROUND: Sigma-54 is a central regulator in many pathogenic bacteria and has been linked to a multitude of cellular processes like nitrogen assimilation and important functional traits such as motility, virulence, and biofilm formation. Until now it has remained obscure whether these phenomena and the control by Sigma-54 share an underlying theme. RESULTS: We have uncovered the commonality by performing a range of comparative genome analyses. A) The presence of Sigma-54 and its associated activators was determined for all sequenced prokaryotes. We observed a phylum-dependent distribution that is suggestive of an evolutionary relationship between Sigma-54 and lipopolysaccharide and flagellar biosynthesis. B) All Sigma-54 activators were identified and annotated. The relation with phosphotransfer-mediated signaling (TCS and PTS) and the transport and assimilation of carboxylates and nitrogen containing metabolites was substantiated. C) The function annotations, that were represented within the genomic context of all genes encoding Sigma-54, its activators and its promoters, were analyzed for intra-phylum representation and inter-phylum conservation. Promoters were localized using a straightforward scoring strategy that was formulated to identify similar motifs. We found clear highly-represented and conserved genetic associations with genes that concern the transport and biosynthesis of the metabolic intermediates of exopolysaccharides, flagella, lipids, lipopolysaccharides, lipoproteins and peptidoglycan. CONCLUSION: Our analyses directly implicate Sigma-54 as a central player in the control over the processes that involve the physical interaction of an organism with its environment like in the colonization of a host (virulence) or the formation of biofilm

Current challenges and future perspectives in oral absorption research: An opinion of the UNGAP network

Although oral drug delivery is the preferred administration route and has been used for centuries, modern drug discovery and development pipelines challenge conventional formulation approaches and highlight the insufficient mechanistic understanding of processes critical to oral drug absorption. This review presents the opinion of UNGAP scientists on four key themes across the oral absorption landscape: (1) specific patient populations, (2) regional differences in the gastrointestinal tract, (3) advanced formulations and (4) food-drug interactions. The differences of oral absorption in pediatric and geriatric populations, the specific issues in colonic absorption, the formulation approaches for poorly water-soluble (small molecules) and poorly permeable (peptides, RNA etc.) drugs, as well as the vast realm of food effects, are some of the topics discussed in detail. The identified controversies and gaps in the current understanding of gastrointestinal absorption-related processes are used to create a roadmap for the future of oral drug absorption research

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

From alcohols to sugars-how does the reactivity of alpha-hydroxyalkyl radicals change with structure? A quantitative examination by pulse radiolysis.

Rate constants are reported for the 1-electron reduction of the azo dye Orange II in water (pH 7.0) by 10 different alpha-hydroxy radicals. The radicals were created by pulse radiolysis of aqueous solutions of the corresponding alcohol/sugar. The rate constants varied from 1 x 10(8) to 2.7 x 10(9) mol(-1) dm(3) s(-1) and radicals with beta-hydroxy groups had the lowest rate constant. The reaction was found to be controlled by the reduction potentials of the radicals, with steric influences having little effects. Good fits of the data were obtained using the Marcus equation with lambda =140 kJ/mol

Sodium dodecyl sulfate-ethoxylated polyethylenimine adsorption at the air-water interface: how the nature of ethoxylation affects the pattern of adsorption.

The strong interaction between ionic surfactants and polyelectrolytes of opposite charge results in enhanced surface adsorption at the air-water interface down to low surfactant concentrations and in some cases in the formation of ordered surface structures. A notable example which exhibits such properties is the mixture of polyethylenimine, PEI, and sodium dodecyl sulfate, SDS. However, the electrostatic interaction, around charge neutralization, between the surfactant and polymer often results in precipitation or coacervation. This can be mitigated for PEI-surfactant mixtures by ethoxylation of the PEI, but this can also result in a weaker surface interaction and a significant reduction in the adsorption. It is shown here that by localizing the ethoxylation of the PEI into discrete regions of the polymer precipitation upon the addition of SDS is suppressed, the strong surface interaction and enhanced adsorption of the polymer-surfactant mixture is retained. The adsorption of SDS in the presence of ethoxylated PEI is greatly enhanced at low SDS concentrations compared to the adsorption for pure SDS. The adsorption is equally pronounced at pH 7 and 10 and is largely independent of the degree of ethoxylation. Surface ordering, more than monolayer adsorption, is observed over a relatively narrow range of SDS concentrations and is most pronounced at pH 10 and for the polymers with the lower degree of ethoxylation. The results show that ethoxylated PEI's reported here provide a suitable route to enhanced surfactant adsorption while retaining favorable solution properties in which precipitation effects are minimized