E151 (sym15), A Pleiotropic Mutant of Pea (Pisum sativum L.), Displays Low Nodule Number, Enhanced Mycorrhizae, Delayed Lateral Root Emergence, and High Root Cytokinin Levels

In legumes, the formation of rhizobial and mycorrhizal root symbioses is a highly regulated process which requires close communication between plant and microorganism. Plant mutants that have difficulties establishing symbioses are valuable tools for unravelling the mechanisms by which these symbioses are formed and regulated. Here E151, a mutant of Pisum sativum cv. Sparkle, was examined to characterize its root growth and symbiotic defects. The symbioses in terms of colonization intensity, functionality of micro-symbionts, and organ dominance were compared between the mutant and wild type. The endogenous cytokinin (CK) and abscisic acid (ABA) levels and the effect of the exogenous application of these two hormones were determined. E151 was found to be a low and delayed nodulator, exhibiting defects in both the epidermal and cortical programmes though a few mature and functional nodules develop. Mycorrhizal colonization of E151 was intensified, although the fungal functionality was impaired. Furthermore, E151 displayed an altered lateral root (LR) phenotype compared with that of the wild type whereby LR emergence is initially delayed but eventually overcome. No differences in ABA levels were found between the mutant and the wild type, but non-inoculated E151 exhibited significantly high CK levels. It is hypothesized that CK plays an essential role in differentially mediating the entry of the two micro-symbionts into the cortex; whereas it would inhibit the entry of the rhizobia in that tissue, it would promote that of the fungus. E151 is a developmental mutant which may prove to be a useful tool in further understanding the role of hormones in the regulation of beneficial root symbioses

Erectile Dysfunction Severity as a Risk Marker for Cardiovascular Disease Hospitalisation and All-Cause Mortality: A Prospective Cohort Study

BACKGROUND Erectile dysfunction is an emerging risk marker for future cardiovascular disease (CVD) events; however, evidence on dose response and specific CVD outcomes is limited. This study investigates the relationship between severity of erectile dysfunction and specific CVD outcomes. METHODS AND FINDINGS We conducted a prospective population-based Australian study (the 45 and Up Study) linking questionnaire data from 2006-2009 with hospitalisation and death data to 30 June and 31 Dec 2010 respectively for 95,038 men aged ≥45 y. Cox proportional hazards models were used to examine the relationship of reported severity of erectile dysfunction to all-cause mortality and first CVD-related hospitalisation since baseline in men with and without previous CVD, adjusting for age, smoking, alcohol consumption, marital status, income, education, physical activity, body mass index, diabetes, and hypertension and/or hypercholesterolaemia treatment. There were 7,855 incident admissions for CVD and 2,304 deaths during follow-up (mean time from recruitment, 2.2 y for CVD admission and 2.8 y for mortality). Risks of CVD and death increased steadily with severity of erectile dysfunction. Among men without previous CVD, those with severe versus no erectile dysfunction had significantly increased risks of ischaemic heart disease (adjusted relative risk [RR] = 1.60, 95% CI 1.31-1.95), heart failure (8.00, 2.64-24.2), peripheral vascular disease (1.92, 1.12-3.29), "other" CVD (1.26, 1.05-1.51), all CVD combined (1.35, 1.19-1.53), and all-cause mortality (1.93, 1.52-2.44). For men with previous CVD, corresponding RRs (95% CI) were 1.70 (1.46-1.98), 4.40 (2.64-7.33), 2.46 (1.63-3.70), 1.40 (1.21-1.63), 1.64 (1.48-1.81), and 2.37 (1.87-3.01), respectively. Among men without previous CVD, RRs of more specific CVDs increased significantly with severe versus no erectile dysfunction, including acute myocardial infarction (1.66, 1.22-2.26), atrioventricular and left bundle branch block (6.62, 1.86-23.56), and (peripheral) atherosclerosis (2.47, 1.18-5.15), with no significant difference in risk for conditions such as primary hypertension (0.61, 0.16-2.35) and intracerebral haemorrhage (0.78, 0.20-2.97). CONCLUSIONS These findings give support for CVD risk assessment in men with erectile dysfunction who have not already undergone assessment. The utility of erectile dysfunction as a clinical risk prediction tool requires specific testing.JC has received research grants from Servier, administered through the University of Sydney and The George Institute, as principal investigator for the ADVANCE trial and ADVANCE-ON post trial follow-up study, and have received honoraria from Servier for speaking about ADVANCE at Scientific meetings. PM has received payment from Pfizer for giving a lecture on the treatment of pulmonary hypertension. All other authors have declared that no competing interests exis

Publisher Correction: An engineered human Fc domain that behaves like a pH-toggle switch for ultra-long circulation persistence.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Variation in readmission and mortality following hospitalisation with a diagnosis of heart failure: prospective cohort study using linked data

BACKGROUND: Hospitalisation for heart failure is common and post-discharge outcomes, including readmission and mortality, are often poor and are poorly understood. The purpose of this study was to examine patient- and hospital-level variation in the risk of 30-day unplanned readmission and mortality following discharge from hospital with a diagnosis of heart failure. METHODS: Prospective cohort study using data from the Sax Institute's 45 and Up Study, linking baseline survey (Jan 2006-April 2009) to hospital and mortality data (to Dec 2011). Primary outcomes in those admitted to hospital with heart failure included unplanned readmission, mortality and combined unplanned readmission/mortality, within 30 days of discharge. Multilevel models quantified the variation in outcomes between hospitals and examined associations with patient- and hospital-level characteristics. RESULTS: There were 5074 participants with a heart failure admission discharged from 251 hospitals; 1052 (21%) had unplanned readmissions, 186 (3.7%) died, and 1146 (23%) had either/both outcomes within 30 days of discharge. Crude outcomes varied across hospitals, but between-hospital variation explained little of the total variation in outcomes (intraclass correlation coefficients (ICC) after inclusion of patient factors: 30-day unplanned readmission ICC = 0.0125 (p = 0.24); death ICC = 0.0000 (p > 0.99); unplanned readmission/death ICC = 0.0266 (p = 0.07)). Patient characteristics associated with a higher risk of unplanned readmission included: being male (male vs female, adjusted odds ratio (aOR) = 1.18, 95% CI: 1.00-1.37); prior hospitalisation for cardiovascular disease (aOR = 1.44, 1.08-1.91) and for anemia (aOR = 1.36, 1.14-1.63); comorbidities at admission (severe vs none: aOR = 1.26, 1.03-1.54); lower body-mass-index (obese vs normal weight: aOR = 0.77, 0.63-0.94); and lower social interaction scores. Similarly, risk of 30-day mortality was associated with patient- rather than hospital-level factors, in particular age (≥85y vs 45-< 75y: aOR = 3.23, 1.93-5.41) and comorbidity (severe vs none: aOR = 2.68, 1.82-3.94). CONCLUSIONS: The issue of high readmission and mortality rates in people with heart failure appear to be system-wide, with the variation in these outcomes essentially attributable to variation between patients rather than hospitals. The findings suggest that there are limitations in using these outcomes as hospital performance measures in this patient population and support the need for patient-centred strategies to optimise heart failure management and outcomes.This specific project was supported by NSW Agency for Clinical Innovation. Emily Banks is supported by the National Health and Medical Research Council of Australia

Groundwater and resilience to drought in the Ethiopian Highlands

During drought, groundwater is often relied on to provide secure drinking water, particularly in rural Africa where other options are limited. However, the technology chosen to access groundwater significantly affects local water security. Here we examine the performance of springs, hand-dug- wells and boreholes in northern Ethiopia through direct high frequency monitoring of water-levels (n=19) and water quality (n=48) over an 18-month period and gathering information on community impacts of declining water access during the El Niño 2015/2016 drought. We found that shallow boreholes equipped with handpumps were the most reliable water supply, recovering within hours to daily abstraction throughout all conditions. Recovery and performance of most hand-dug-wells and springs declined significantly throughout the extended dry season, although in specific aquifer conditions they were reliable. All sources types had negligible measured contamination from Thermo-tolerant Coliforms through the extended dry season, but were contaminated during the rains marking drought cessation. Boreholes were least affected, median 10 cfu/100ml, compared to 190 and 59 cfu/100ml for hand-dug-wells and springs respectively. Many communities who relied solely on springs, wells or rivers experienced severe water shortage in the El Niño drought with mean daily collection times up to 12 hours and volumes collected reducing to 3-5 litre- per-capita- per-day. This led to reports of violent conflict, missed meals, reduction in school attendance and farm activity and increased health impacts. From this study there is a clear case for improving resilience to drought by installing boreholes equipped with handpumps where feasible even if collection times are >30 minutes

Possible futures for groundwater in Burkina Faso under a changing climate

This narrative describes three possible future scenarios for water resources in Burkina Faso and the human and socio-economic impacts that might be experienced by people living in rural areas. The narratives aim to stimulate discussion towards realistic policy responses and the decision support tools needed to assist future planning needs. It is important to recognise that the scenarios do not represent every possible outcome projected by hydroclimate models, and resulting impacts will be contextualised by local circumstances. See here for information about BRAVE (www.walker.ac.uk) and the UPGro programme: upgro.org/consortium/brave2/

A Green Bank Telescope search for narrowband technosignatures between 1.1-1.9 GHz during 12 Kepler planetary transits

A growing avenue for determining the prevalence of life beyond Earth is to search for "technosignatures" from extraterrestrial intelligences/agents. Technosignatures require significant energy to be visible across interstellar space and thus intentional signals might be concentrated in frequency, in time, or in space, to be found in mutually obvious places. Therefore, it could be advantageous to search for technosignatures in parts of parameter space that are mutually-derivable to an observer on Earth and a distant transmitter. In this work, we used the L-band (1.1-1.9 GHz) receiver on the Robert C. Byrd Green Bank Telescope (GBT) to perform the first technosignature search pre-synchronized with exoplanet transits, covering 12 Kepler systems. We used the Breakthrough Listen turboSETI pipeline to flag narrowband hits ($\sim$3 Hz) using a maximum drift rate of $\pm$614.4 Hz/s and a signal-to-noise threshold of 5 - the pipeline returned $\sim 3.4 \times 10^5$ apparently-localized features. Visual inspection by a team of citizen scientists ruled out 99.6% of them. Further analysis found 2 signals-of-interest that warrant follow-up, but no technosignatures. If the signals-of-interest are not re-detected in future work, it will imply that the 12 targets in the search are not producing transit-aligned signals from 1.1-1.9 GHz with transmitter powers $>$60 times that of the former Arecibo radar. This search debuts a range of innovative technosignature techniques: citizen science vetting of potential signals-of-interest, a sensitivity-aware search out to extremely high drift rates, a more flexible method of analyzing on-off cadences, and an extremely low signal-to-noise threshold.Comment: 18 pages, 11 figure

The neutrophil antimicrobial peptide cathelicidin promotes Th17 differentiation

The host defence peptide cathelicidin (LL-37 in humans, mCRAMP in mice) is released from neutrophils by de-granulation, NETosis and necrotic death; it has potent anti-pathogen activity as well as being a broad immunomodulator. Here we report that cathelicidin is a powerful Th17 potentiator which enhances aryl hydrocarbon receptor (AHR) and RORγt expression, in a TGF-β1-dependent manner. In the presence of TGF-β1, cathelicidin enhanced SMAD2/3 and STAT3 phosphorylation, and profoundly suppressed IL-2 and T-bet, directing T cells away from Th1 and into a Th17 phenotype. Strikingly, Th17 but not Th1 cells were protected from apoptosis by cathelicidin. We show that cathelicidin is released by neutrophils in mouse lymph nodes and that cathelicidin-deficient mice display suppressed Th17 responses during inflammation, but not at steady state. We propose that the neutrophil cathelicidin is required for maximal Th17 differentiation, and that this is one method by which early neutrophilia directs subsequent adaptive immune responses

How Design Features in Digital Math Games Support Learning and Mathematics Connections

Current research shows that digital games can significantly enhance children’s learning. The purpose of this study was to examine how design features in 12 digital math games influenced children’s learning. The participants in this study were 193 children in Grades 2 through 6 (ages 8-12). During clinical interviews, children in the study completed pre-tests, interacted with digital math games, responded to questions about the digital math games, and completed post-tests. We recorded the interactions using two video perspectives that recorded children’s gameplay and responses to interviewers. We employed mixed methods to analyze the data and identify salient patterns in children’s experiences with the digital math games. The analysis revealed significant gains for 9 of the 12 digital games and most children were aware of the design features in the games. There were eight prominent categories of design features in the video data that supported learning and mathematics connections. Six categories focused on how the design features supported learning in the digital games. These categories included: accuracy feedback, unlimited/multiple attempts, information tutorials and hints, focused constraint, progressive levels, and game efficiency. Two categories were more specific to embodied cognition and action with the mathematics, and focused on how design features promoted mathematics connections. These categories included: linked representations and linked physical actions. The digital games in this study that did not include linked representations and opportunities for linked physical actions as design features did not produce significant gains. These results suggest the key role of mathematics-specific design features in the design of digital math games