Identification of potential drug targets in Salmonella Typhimurium using metabolic modelling and experimental validation

almonella enterica serovar Typhimurium is an established model organism for Gram-negative, intracellular pathogens. Owing to the rapid spread of resistance to antibiotics among this group of pathogens, new approaches to identify suitable target proteins are required. Based on the genome sequence of Salmonella Typhimurium and associated databases, a genome-scale metabolic model was constructed. Output was based on an experimental determination of the biomass of Salmonella when growing in glucose minimal medium. Linear programming was used to simulate variations in energy demand, while growing in glucose minimal medium. By grouping reactions with similar flux responses, a sub-network of 34 reactions responding to this variation was identified (the catabolic core). This network was used to identify sets of one and two reactions, that when removed from the genome-scale model interfered with energy and biomass generation. 11 such sets were found to be essential for the production of biomass precursors. Experimental investigation of 7 of these showed that knock-outs of the associated genes resulted in attenuated growth for 4 pairs of reactions, while 3 single reactions were shown to be essential for growth.

How do people perceive, understand, and anticipate responding to flash flood risks and warnings? Results from a public survey in Boulder, Colorado, USA

This study investigates flash flood forecast and warning communication, interpretation, and decision making, using data from a survey of 418 members of the public in Boulder, Colorado, USA. Respondents to the public survey varied in their perceptions and understandings of flash flood risks in Boulder, and some had misconceptions about flash flood risks, such as the safety of crossing fast-flowing water. About 6% of respondents indicated consistent reversals of US watch-warning alert terminology. However, more in-depth analysis illustrates the multi-dimensional, situationally dependent meanings of flash flood alerts, as well as the importance of evaluating interpretation and use of warning information along with alert terminology. Some public respondents estimated low likelihoods of flash flooding given a flash flood warning; these were associated with lower anticipated likelihood of taking protective action given a warning. Protective action intentions were also lower among respondents who had less trust in flash flood warnings, those who had not made prior preparations for flash flooding, and those who believed themselves to be safer from flash flooding. Additional analysis, using open-ended survey questions about responses to warnings, elucidates the complex, contextual nature of protective decision making during flash flood threats. These findings suggest that warnings can play an important role not only by notifying people that there is a threat and helping motivate people to take protective action, but also by helping people evaluate what actions to take given their situation.