Adaptable Functionality of Transcriptional Feedback in Bacterial Two-Component Systems

A widespread mechanism of bacterial signaling occurs through two-component systems, comprised of a sensor histidine kinase (SHK) and a transcriptional response regulator (RR). The SHK activates RR by phosphorylation. The most common two-component system structure involves expression from a single operon, the transcription of which is activated by its own phosphorylated RR. The role of this feedback is poorly understood, but it has been associated with an overshooting kinetic response and with fast recovery of previous interrupted signaling events in different systems. Mathematical models show that overshoot is only attainable with negative feedback that also improves response time. Our models also predict that fast recovery of previous interrupted signaling depends on high accumulation of SHK and RR, which is more likely in a positive feedback regime. We use Monte Carlo sampling of the parameter space to explore the range of attainable model behaviors. The model predicts that the effective feedback sign can change from negative to positive depending on the signal level. Variations in two-component system architectures and parameters may therefore have evolved to optimize responses in different bacterial lifestyles. We propose a conceptual model where low signal conditions result in a responsive system with effectively negative feedback while high signal conditions with positive feedback favor persistence of system output

World guidelines for falls prevention and management for older adults: a global initiative

Background: falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. Current guidelines are inconsistent, with no up-to-date, globally applicable ones present. Objectives: to create a set of evidence- and expert consensus-based falls prevention and management recommendations applicable to older adults for use by healthcare and other professionals that consider: (i) a person-centred approach that includes the perspectives of older adults with lived experience, caregivers and other stakeholders; (ii) gaps in previous guidelines; (iii) recent developments in e-health and (iv) implementation across locations with limited access to resources such as low- and middle-income countries. Methods: a steering committee and a worldwide multidisciplinary group of experts and stakeholders, including older adults, were assembled. Geriatrics and gerontological societies were represented. Using a modified Delphi process, recommendations from 11 topic-specific working groups (WGs), 10 ad-hoc WGs and a WG dealing with the perspectives of older adults were reviewed and refined. The final recommendations were determined by voting. Recommendations: all older adults should be advised on falls prevention and physical activity. Opportunistic case finding for falls risk is recommended for community-dwelling older adults. Those considered at high risk should be offered a comprehensive multifactorial falls risk assessment with a view to co-design and implement personalised multidomain interventions. Other recommendations cover details of assessment and intervention components and combinations, and recommendations for specific settings and populations. Conclusions: the core set of recommendations provided will require flexible implementation strategies that consider both local context and resources

An in vitro mucosal model for prediction of the bioadhesion of alginate solutions to the oesophagus

This paper discusses the development of an in vitro model utilised to assess the adhesion of alginate solutions to porcine oesophageal tissue. The methodology involved the construction of retention apparatus onto which sections of tissue were mounted. Fluorescently labelled alginate solutions of known rheological profile were dispensed onto the tissue at a concentration of 2% w/v. A washing solution was applied at a specified rate to mimic saliva flow and the eluted material collected. Fluorimetric analysis allowed dose retention to be assessed as a function of time. The effect of the nature of the washing solution and the choice of alginate were investigated. It was found that after 30 min up to 20% of the applied alginate dose remained associated with the tissue, regardless of the alginate selected from the range examined. The nature of the washing medium did not have a significant effect on retention, irrespective of the inherent mucin concentration. Overall this study indicated that the technique presented offers a viable means of studying bioadhesion of liquids and also demonstrates that alginate solutions may have an application as bioadhesive agents for localisation within the oesophagus