Molecular decoding using luminescence from an entangled porous framework

Chemosensors detect a single target molecule from among several molecules, but cannot differentiate targets from one another. In this study, we report a molecular decoding strategy in which a single host domain accommodates a class of molecules and distinguishes between them with a corresponding readout. We synthesized the decoding host by embedding naphthalenediimide into the scaffold of an entangled porous framework that exhibited structural dynamics due to the dislocation of two chemically non-interconnected frameworks. An intense turn-on emission was observed on incorporation of a class of aromatic compounds, and the resulting luminescent colour was dependent on the chemical substituent of the aromatic guest. This unprecedented chemoresponsive, multicolour luminescence originates from an enhanced naphthalenediimide–aromatic guest interaction because of the induced-fit structural transformation of the entangled framework. We demonstrate that the cooperative structural transition in mesoscopic crystal domains results in a nonlinear sensor response to the guest concentration

Impact of national malaria control scale-up programmes in Africa: magnitude and attribution of effects

<p>Abstract</p> <p>Background</p> <p>Since 2005, malaria control scale-up has progressed in many African countries. Controlled studies of insecticide-treated mosquito nets (ITNs), indoor residual spraying (IRS), intermittent preventive treatment during pregnancy (IPTp) and malaria case management suggested that when incorporated into national programmes a dramatic health impact, likely more than a 20% decrease in all-cause childhood mortality, was possible. To assess the extent to which national malaria programmes are achieving impact the authors reviewed African country programme data available through 2009.</p> <p>Methods</p> <p>National survey data, published literature, and organization or country reports produced during 2000-2009 were reviewed to assess available malaria financing, intervention delivery, household or target population coverage, and reported health benefits including infection, illness, severe anaemia, and death.</p> <p>Results</p> <p>By the end of 2009, reports were available for ITN household ownership (n = 34) and IPTp use (n = 27) in malaria-endemic countries in Africa, with at least two estimates (pre-2005 and post-2005 intervals). Information linking IRS and case management coverage to impact were more limited. There was generally at least a three-fold increase in household ITN ownership across these countries between pre-2005 (median of 2.4% of households with at least one ITN) and post-2005 (median of 32.5% of households with at least one ITN). Ten countries had temporal data to assess programme impact, and all reported progress on at least one impact indicator (typically on mortality); in under-five year mortality rates most observed a decline of more than 20%. The causal relationship between malaria programme scale-up and reduced child illness and mortality rates is supported by biologic plausibility including mortality declines consistent with experience from intervention efficacy trials, consistency of findings across multiple countries and different epidemiologic settings, and temporal congruity where morbidity and mortality declines have been documented in the 18 to 36 months following intervention scale-up.</p> <p>Conclusions</p> <p>Several factors potentially have contributed to recent health improvement in African countries, but there is substantial evidence that achieving high malaria control intervention coverage, especially with ITNs and targeted IRS, has been the leading contributor to reduced child mortality. The documented impact provides the evidence required to support a global commitment to the expansion and long-term investment in malaria control to sustain and increase the health impact that malaria control is producing in Africa.</p

Universal Sequence Replication, Reversible Polymerization and Early Functional Biopolymers: A Model for the Initiation of Prebiotic Sequence Evolution

Many models for the origin of life have focused on understanding how evolution can drive the refinement of a preexisting enzyme, such as the evolution of efficient replicase activity. Here we present a model for what was, arguably, an even earlier stage of chemical evolution, when polymer sequence diversity was generated and sustained before, and during, the onset of functional selection. The model includes regular environmental cycles (e.g. hydration-dehydration cycles) that drive polymers between times of replication and functional activity, which coincide with times of different monomer and polymer diffusivity. Template-directed replication of informational polymers, which takes place during the dehydration stage of each cycle, is considered to be sequence-independent. New sequences are generated by spontaneous polymer formation, and all sequences compete for a finite monomer resource that is recycled via reversible polymerization. Kinetic Monte Carlo simulations demonstrate that this proposed prebiotic scenario provides a robust mechanism for the exploration of sequence space. Introduction of a polymer sequence with monomer synthetase activity illustrates that functional sequences can become established in a preexisting pool of otherwise non-functional sequences. Functional selection does not dominate system dynamics and sequence diversity remains high, permitting the emergence and spread of more than one functional sequence. It is also observed that polymers spontaneously form clusters in simulations where polymers diffuse more slowly than monomers, a feature that is reminiscent of a previous proposal that the earliest stages of life could have been defined by the collective evolution of a system-wide cooperation of polymer aggregates. Overall, the results presented demonstrate the merits of considering plausible prebiotic polymer chemistries and environments that would have allowed for the rapid turnover of monomer resources and for regularly varying monomer/polymer diffusivities

Checkpoints in a Yeast Differentiation Pathway Coordinate Signaling during Hyperosmotic Stress

All eukaryotes have the ability to detect and respond to environmental and hormonal signals. In many cases these signals evoke cellular changes that are incompatible and must therefore be orchestrated by the responding cell. In the yeast Saccharomyces cerevisiae, hyperosmotic stress and mating pheromones initiate signaling cascades that each terminate with a MAP kinase, Hog1 and Fus3, respectively. Despite sharing components, these pathways are initiated by distinct inputs and produce distinct cellular behaviors. To understand how these responses are coordinated, we monitored the pheromone response during hyperosmotic conditions. We show that hyperosmotic stress limits pheromone signaling in at least three ways. First, stress delays the expression of pheromone-induced genes. Second, stress promotes the phosphorylation of a protein kinase, Rck2, and thereby inhibits pheromone-induced protein translation. Third, stress promotes the phosphorylation of a shared pathway component, Ste50, and thereby dampens pheromone-induced MAPK activation. Whereas all three mechanisms are dependent on an increase in osmolarity, only the phosphorylation events require Hog1. These findings reveal how an environmental stress signal is able to postpone responsiveness to a competing differentiation signal, by acting on multiple pathway components, in a coordinated manner

Influence of phosphorus on copper sensitivity of fluvial periphyton: the role of chemical, physiological and community-related factors

The influence of eutrophication of fluvial ecosystems (caused by increased phosphorus concentrations) on periphyton Cu sensitivity is explored from a multi-scale perspective, going from the field to the laboratory. The study design included three tiers: a field study including the characterization of land use and the ecological state of the corresponding river sections in the Fluvià River watershed, an experimental investigation performed with natural periphyton from the previously studied stream sites in indoor channels, and finally a culture study in the laboratory. Results showed that differences in copper sensitivity of natural periphyton communities followed the gradient of nutrient concentration found in the field. Results from the culture experiments demonstrated that both, P-conditions during growth and P-content in the media are important factors modulating the toxicological response of algae to Cu. The observations from this study indicate that the ecological effects of metal pollution in rivers might be obscured by eutrophication

Global Diversity of Brittle Stars (Echinodermata: Ophiuroidea)

This review presents a comprehensive overview of the current status regarding the global diversity of the echinoderm class Ophiuroidea, focussing on taxonomy and distribution patterns, with brief introduction to their anatomy, biology, phylogeny, and palaeontological history. A glossary of terms is provided. Species names and taxonomic decisions have been extracted from the literature and compiled in The World Ophiuroidea Database, part of the World Register of Marine Species (WoRMS). Ophiuroidea, with 2064 known species, are the largest class of Echinodermata. A table presents 16 families with numbers of genera and species. The largest are Amphiuridae (467), Ophiuridae (344 species) and Ophiacanthidae (319 species). A biogeographic analysis for all world oceans and all accepted species was performed, based on published distribution records. Approximately similar numbers of species were recorded from the shelf (n = 1313) and bathyal depth strata (1297). The Indo-Pacific region had the highest species richness overall (825 species) and at all depths. Adjacent regions were also relatively species rich, including the North Pacific (398), South Pacific (355) and Indian (316) due to the presence of many Indo-Pacific species that partially extended into these regions. A secondary region of enhanced species richness was found in the West Atlantic (335). Regions of relatively low species richness include the Arctic (73 species), East Atlantic (118), South America (124) and Antarctic (126)

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

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders