Structural basis for Fullerene geometry in a human endogenous retrovirus capsid

The HML2 (HERV-K) group constitutes the most recently acquired family of human endogenous retroviruses, with many proviruses less than one million years old. Many maintain intact open reading frames and provirus expression together with HML2 particle formation are observed in early stage human embryo development and are associated with pluripotency as well as inflammatory disease, cancers and HIV-1 infection. Here, we reconstruct the core structural protein (CA) of an HML2 retrovirus, assemble particles in vitro and employ single particle cryogenic electron microscopy (cryo-EM) to determine structures of four classes of CA Fullerene shell assemblies. These icosahedral and capsular assemblies reveal at high-resolution the molecular interactions that allow CA to form both pentamers and hexamers and show how invariant pentamers and structurally plastic hexamers associate to form the unique polyhedral structures found in retroviral cores

Genetic testing of children for adult-onset conditions: opinions of the British adult population and implications for clinical practice

This study set out to explore the attitudes of a representative sample of the British public towards genetic testing in children to predict disease in the future. We sought opinions about genetic testing for adult-onset conditions for which no prevention/treatment is available during childhood, and about genetic 'carrier' status to assess future reproductive risks. The study also examined participants' level of agreement with the reasons professional organisations give in favour of deferring such testing. Participants (n=2998) completed a specially designed questionnaire, distributed by email. Nearly half of the sample (47%) agreed that parents should be able to test their child for adult-onset conditions, even if there is no treatment or prevention at time of testing. This runs contrary to professional guidance about genetic testing in children. Testing for carrier status was supported by a larger proportion (60%). A child's future ability to decide for her/himself if and when to be tested was the least supported argument in favour of deferring testing.European Journal of Human Genetics advance online publication, 5 November 2014; doi:10.1038/ejhg.2014.221

The elastic constants of MgSiO3 perovskite at pressures and temperatures of the Earth's mantle

The temperature anomalies in the Earth's mantle associated with thermal convection1 can be inferred from seismic tomography, provided that the elastic properties of mantle minerals are known as a function of temperature at mantle pressures. At present, however, such information is difficult to obtain directly through laboratory experiments. We have therefore taken advantage of recent advances in computer technology, and have performed finite-temperature ab initio molecular dynamics simulations of the elastic properties of MgSiO3 perovskite, the major mineral of the lower mantle, at relevant thermodynamic conditions. When combined with the results from tomographic images of the mantle, our results indicate that the lower mantle is either significantly anelastic or compositionally heterogeneous on large scales. We found the temperature contrast between the coldest and hottest regions of the mantle, at a given depth, to be about 800K at 1000 km, 1500K at 2000 km, and possibly over 2000K at the core-mantle boundary.Comment: Published in: Nature 411, 934-937 (2001

Syntactic processing as a marker for cognitive impairment in amyotrophic lateral sclerosis

Despite recent interest in cognitive changes in patients with amyotrophic lateral sclerosis (ALS), investigations of language function looking at the level of word, sentence and discourse processing are relatively scarce. Data were obtained from 26 patients with sporadic ALS and 26 healthy controls matched for age, education, gender, anxiety, depression and executive function performance. Standardized language tasks included confrontation naming, semantic access, and syntactic comprehension. Quantitative production analysis (QPA) was used to analyse connected speech samples of the Cookie Theft picture description task. Results showed that the ALS patients were impaired on standardized measures of grammatical comprehension and action/verb semantics. At the level of discourse, ALS patients were impaired on measures of syntactic complexity and fluency; however, the latter could be better explained by disease related factors. Discriminant analysis revealed that syntactic measures differentiated ALS patients from controls. In conclusion, patients with ALS exhibit deficits in receptive and expressive language on tasks of comprehension and connected speech production, respectively. Our findings suggest that syntactic processing deficits seem to be the predominant feature of language impairment in ALS and that these deficits can be detected by relatively simple language tests

Monolithically integrated heterodyne optical phase-lock loop with RF XOR phase detector

We present results for an heterodyne optical phase-lock loop (OPLL), monolithically integrated on InP with external phase detector and loop filter, which phase locks the integrated laser to an external source, for offset frequencies tuneable between 0.6 GHz and 6.1 GHz. The integrated semiconductor laser emits at 1553 nm with 1.1 MHz linewidth, while the external laser has a linewidth less than 150 kHz. To achieve high quality phase locking with lasers of these linewidths, the loop delay has been made less than 1.8 ns. Monolithic integration reduces the optical path delay between the laser and photodiode to less than 20 ps. The electronic part of the OPLL was implemented using a custom-designed feedback circuit with a propagation delay of similar to 1 ns and an open-loop bandwidth greater than 1 GHz. The heterodyne signal between the locked slave laser and master laser has phase noise below. 90 dBc/Hz for frequency offsets greater than 20 kHz and a phase error variance in 10 GHz bandwidth of 0.04 rad(2). (C) 2011 Optical Society of Americ

Policy windows for the environment: Tips for improving the uptake of scientific knowledge

© 2017 The Authors. Scientific knowledge is considered to be an important factor (alongside others) in environmental policy-making. However, the opportunity for environmentalists to influence policy can often occur within short, discrete time windows. Therefore, a piece of research may have a negligible or transformative policy influence depending on when it is presented. These ‘policy windows’ are sometimes predictable, such as those dealing with conventions or legislation with a defined renewal period, but are often hard to anticipate. We describe four ways that environmentalists can respond to policy windows and increase the likelihood of knowledge uptake: 1) foresee (and create) emergent windows, 2) respond quickly to opening windows, 3) frame research in line with appropriate windows, and 4) persevere in closed windows. These categories are closely linked; efforts to enhance the incorporation of scientific knowledge into policy need to harness mechanisms within each. We illustrate the main points with reference to nature conservation, but the principles apply widely.European Union Seventh Framework Programme EU Biodiversity Observation Network (No. 308454); Fondation Wiener Anspach, Belgium; Scriven fellowship; Natural Environment Research Council Cambridge Earth System Science NERC DTP [NE/L002507/1]; Natural Environment Research Council Industrial CASE studentship [NE/M010287/1]; Austrian Science Fund (FWF); Arcadia

High-dose intravenous iron reduces myocardial infarction in patients on haemodialysis

AIMS: To investigate the effect of high-dose iron vs. low-dose intravenous (IV) iron on myocardial infarction (MI) in patients on maintenance haemodialysis. METHODS AND RESULTS: This was a pre-specified analysis of secondary endpoints of the Proactive IV Iron Therapy in Hemodialysis Patients trial (PIVOTAL) randomized, controlled clinical trial. Adults who had started haemodialysis within the previous year, who had a ferritin concentration <400 μg per litre and a transferrin saturation <30% were randomized to high-dose or low-dose IV iron. The main outcome measure for this analysis was fatal or non-fatal MI. Over a median of 2.1 years of follow-up, 8.4% experienced a MI. Rates of type 1 MIs (3.2/100 patient-years) were 2.5 times higher than type 2 MIs (1.3/100 patient-years). Non-ST-elevation MIs (3.3/100 patient-years) were 6 times more common than ST-elevation MIs (0.5/100 patient-years). Mortality was high after non-fatal MI (1- and 2-year mortality of 40% and 60%, respectively). In time-to-first event analyses, proactive high-dose IV iron reduced the composite endpoint of non-fatal and fatal MI [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.52-0.93, P = 0.01] and non-fatal MI (HR 0.69, 95% CI 0.51-0.93; P = 0.01) when compared with reactive low-dose IV iron. There was less effect of high-dose IV iron on recurrent MI events than on the time-to-first event analysis. CONCLUSION: In total, 8.4% of patients on maintenance haemodialysis had an MI over 2 years. High-dose compared to low-dose IV iron reduced MI in patients receiving haemodialysis. EUDRACT REGISTRATION NUMBER: 2013-002267-25

Policy windows for the environment: Tips for improving the uptake of scientific knowledge

Scientific knowledge is considered to be an important factor (alongside others) in environmental policy-making. However, the opportunity for environmentalists to influence policy can often occur within short, discrete time windows. Therefore, a piece of research may have a negligible or transformative policy influence depending on when it is presented. These ‘policy windows’ are sometimes predictable, such as those dealing with conventions or legislation with a defined renewal period, but are often hard to anticipate. We describe four ways that environmentalists can respond to policy windows and increase the likelihood of knowledge uptake: 1) foresee (and create) emergent windows, 2) respond quickly to opening windows, 3) frame research in line with appropriate windows, and 4) persevere in closed windows. These categories are closely linked; efforts to enhance the incorporation of scientific knowledge into policy need to harness mechanisms within each. We illustrate the main points with reference to nature conservation, but the principles apply widely.(1) EU’s Seventh Framework Programme within the EU Biodiversity Observation Network (No. 308454) (2) Post-doctoral fellowship from Fondation Wiener Anspach, Belgium and the Scriven fellowship, (3) Cambridge Earth System Science NERC DTP [NE/L002507/1], (4) Austrian Science Fund (FWF), (5) Arcadia

Heart Failure Hospitalization in Adults Receiving Hemodialysis and the Effect of Intravenous Iron Therapy

OBJECTIVES: This study sought to examine the effect of intravenous iron on heart failure events in hemodialysis patients. BACKGROUND: Heart failure is a common and deadly complication in patients receiving hemodialysis and is difficult to diagnose and treat. METHODS: The study analyzed heart failure events in the PIVOTAL (Proactive IV Iron Therapy in Hemodialysis Patients) trial, which compared intravenous iron administered proactively in a high-dose regimen with a low-dose regimen administered reactively. Heart failure hospitalization was an adjudicated outcome, a component of the primary composite outcome, and a prespecified secondary endpoint in the trial. RESULTS: Overall, 2,141 participants were followed for a median of 2.1 years. A first fatal or nonfatal heart failure event occurred in 51 (4.7%) of 1,093 patients in the high-dose iron group and in 70 (6.7%) of 1,048 patients in the low-dose group (HR: 0.66; 95% CI: 0.46-0.94; P = 0.023). There was a total of 63 heart failure events (including first and recurrent events) in the high-dose iron group and 98 in the low-dose group, giving a rate ratio of 0.59 (95% CI: 0.40-0.87; P = 0.0084). Most patients presented with pulmonary edema and were mainly treated by mechanical removal of fluid. History of heart failure and diabetes were independent predictors of a heart failure event. CONCLUSIONS: Compared with a lower-dose regimen, high-dose intravenous iron decreased the occurrence of first and recurrent heart failure events in patients undergoing hemodialysis, with large relative and absolute risk reductions. (UK Multicentre Open-label Randomised Controlled Trial Of IV Iron Therapy In Incident Haemodialysis Patients; 2013-002267-25)