Fossilized skin reveals coevolution with feathers and metabolism in feathered dinosaurs and early birds

Feathers are remarkable evolutionary innovations that are associated with complex adaptations of the skin in modern birds. Fossilised feathers in non-avian dinosaurs and basal birds provide insights into feather evolution, but how associated integumentary adaptations evolved is unclear. Here we report the discovery of fossil skin, preserved with remarkable nanoscale fidelity, in three non-avian maniraptoran dinosaurs and a basal bird from the Cretaceous Jehol biota (China). The skin comprises patches of desquamating epidermal corneocytes that preserve a cytoskeletal array of helically coiled α-keratin tonofibrils. This structure confirms that basal birds and non-avian dinosaurs shed small epidermal flakes as in modern mammals and birds, but structural differences imply that these Cretaceous taxa had lower body heat production than modern birds. Feathered epidermis acquired many, but not all, anatomically modern attributes close to the base of the Maniraptora by the Middle Jurassic

From social contract to 'social contrick' : the depoliticisation of economic policy-making under Harold Wilson, 1974–75

The 1974-79 Labour Governments were elected on the basis of an agreement with the TUC promising a redistribution of income and wealth known as the Social Contract. However, the Government immediately began to marginalise these commitments in favour of preferences for incomes policy and public expenditure cuts, which has led the Social Contract to be described as the 'Social Contrick'. These changes were legitimised through a process of depoliticisation, and using an Open Marxist framework and evidence from the National Archives, the paper will show that the Treasury's exchange rate strategy and the need to secure external finance placed issues of confidence at the centre of political debate, allowing the Government to argue there was no alternative to the introduction of incomes policy and the reduction of public expenditure

Survey of variation in human transcription factors reveals prevalent DNA binding changes

Published in final edited form as: Science. 2016 Mar 25; 351(6280): 1450–1454. Published online 2016 Mar 24. doi: 10.1126/science.aad2257Sequencing of exomes and genomes has revealed abundant genetic variation affecting the coding sequences of human transcription factors (TFs), but the consequences of such variation remain largely unexplored. We developed a computational, structure-based approach to evaluate TF variants for their impact on DNA binding activity and used universal protein-binding microarrays to assay sequence-specific DNA binding activity across 41 reference and 117 variant alleles found in individuals of diverse ancestries and families with Mendelian diseases. We found 77 variants in 28 genes that affect DNA binding affinity or specificity and identified thousands of rare alleles likely to alter the DNA binding activity of human sequence-specific TFs. Our results suggest that most individuals have unique repertoires of TF DNA binding activities, which may contribute to phenotypic variation.National Institutes of Health; NHGRI R01 HG003985; P50 HG004233; A*STAR National Science Scholarship; National Science Foundatio

Formation of Super-Earths

Super-Earths are the most abundant planets known to date and are characterized by having sizes between that of Earth and Neptune, typical orbital periods of less than 100 days and gaseous envelopes that are often massive enough to significantly contribute to the planet's overall radius. Furthermore, super-Earths regularly appear in tightly-packed multiple-planet systems, but resonant configurations in such systems are rare. This chapters summarizes current super-Earth formation theories. It starts from the formation of rocky cores and subsequent accretion of gaseous envelopes. We follow the thermal evolution of newly formed super-Earths and discuss their atmospheric mass loss due to disk dispersal, photoevaporation, core-cooling and collisions. We conclude with a comparison of observations and theoretical predictions, highlighting that even super-Earths that appear as barren rocky cores today likely formed with primordial hydrogen and helium envelopes and discuss some paths forward for the future.Comment: Invited review accepted for publication in the 'Handbook of Exoplanets,' Planet Formation section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Ed

A national registry to assess the value of cardiovascular magnetic resonance imaging after primary percutaneous coronary intervention pathway activation:a feasibility cohort study

Background Cardiovascular magnetic resonance (CMR) is increasingly used in patients who activate the primary percutaneous coronary intervention (PPCI) pathway to assess heart function. It is uncertain whether having CMR influences patient management or the risk of major adverse cardiovascular events in these patients. Objective To determine whether or not it is feasible to set up a national registry, linking routinely collected data from hospital information systems (HISs), to investigate the role of CMR in patients who activate the PPCI pathway. Design A feasibility prospective cohort study. Setting Four 24/7 PPCI hospitals in England and Wales (two with and two without a dedicated CMR facility). Participants Patients who activated the PPCI pathway and underwent an emergency coronary angiogram. Interventions CMR either performed or not performed within 10 weeks of the index event. Main outcome measures A. Feasibility parameters – (1) patient consent implemented at all hospitals, (2) data extracted from more than one HIS and successfully linked for andgt; 90% of consented patients at all four hospitals, (3) HIS data successfully linked with Hospital Episode Statistics (HES) and Patient Episode Database Wales (PEDW) for andgt; 90% of consented patients at all four hospitals and (4) CMR requested and carried out for ≥ 10% of patients activating the PPCI pathway in CMR hospitals. B. Key drivers of cost-effectiveness for CMR (identified from simple cost-effectiveness models) in patients with (1) multivessel disease and (2) unobstructed coronary arteries. C. A change in clinical management arising from having CMR (defined using formal consensus and identified using HES follow-up data in the 12 months after the index event). Results A. (1) Consent was implemented (for all hospitals, consent rates were 59–74%) and 1670 participants were recruited. (2) Data submission was variable – clinical data available for ≥ 82% of patients across all hospitals, biochemistry and echocardiography (ECHO) data available for ≥ 98%, 34% and 87% of patients in three hospitals and medications data available for 97% of patients in one hospital. (3) HIS data were linked with hospital episode data for 99% of all consented patients. (4) At the two CMR hospitals, 14% and 20% of patients received CMR. B. In both (1) multivessel disease and (2) unobstructed coronary arteries, the difference in quality-adjusted life-years (QALYs) between CMR and no CMR [‘current’ comparator, stress ECHO and standard ECHO, respectively] was very small [0.0012, 95% confidence interval (CI) –0.0076 to 0.0093 and 0.0005, 95% CI –0.0050 to 0.0077, respectively]. The diagnostic accuracy of the ischaemia tests was the key driver of cost-effectiveness in sensitivity analyses for both patient subgroups. C. There was consensus that CMR leads to clinically important changes in management in five patient subgroups. Some changes in management were successfully identified in hospital episode data (e.g. new diagnoses/procedures, frequency of outpatient episodes related to cardiac events), others were not (e.g. changes in medications, new diagnostic tests). Conclusions A national registry is not currently feasible. Patients were consented successfully but conventional consent could not be implemented nationally. Linking HIS and hospital episode data was feasible but HIS data were not uniformly available. It is feasible to identify some, but not all, changes in management in the five patient subgroups using hospital episode data. The delay in obtaining hospital episode data influenced the relevance of some of our study objectives. Future work To test the feasibility of conducting the study using national data sets (e.g. HES, British Cardiovascular Intervention Society audit database, Diagnostic Imaging Dataset, Clinical Practice Research Datalink). Funding The National Institute for Health Research (NIHR) Health Services and Delivery Research programme. This study was designed and delivered in collaboration with the Clinical Trials and Evaluation Unit, a UK Clinical Research Collaboration-registered clinical trials unit that, as part of the Bristol Trials Centre, is in receipt of NIHR clinical trials unit support funding. </jats:sec

Real-time energy storage simulators for the electricity grid

In this paper, a novel Distributed Real-Time Simulation Environment (DRTSE) which enables the coordinated control of multiple Real-Time Simulators (RTSs) positioned across the UK is introduced and demonstrated for an energy storage application. Using RTSs instead of physical energy storage assets enables the testing of different communication and control strategies, thereby reducing the risk of failure when the physical storage assets are deployed. In addition, the testing of different storage types (e.g. batteries, compressed air, flywheels, etc.) and storage locations can be conducted without expensive hardware modifications. In this paper, technical details of the RTSs are given, including the hardware and electrical storage models. The Central Controller (CC) and communication are also described, and results from the DRTSE presented

Engineering tyrosine-based electron flow pathways in proteins: The case of aplysia myoglobin

Tyrosine residues can act as redox cofactors that provide an electron transfer ("hole-hopping") route that enhances the rate of ferryl heme iron reduction by externally added reductants, for example, ascorbate. Aplysia fasciata myoglobin, having no naturally occurring tyrosines but 15 phenylalanines that can be selectively mutated to tyrosine residues, provides an ideal protein with which to study such through-protein electron transfer pathways and ways to manipulate them. Two surface exposed phenylalanines that are close to the heme have been mutated to tyrosines (F42Y, F98Y). In both of these, the rate of ferryl heme reduction increased by up to 3 orders of magnitude. This result cannot be explained in terms of distance or redox potential change between donor and acceptor but indicates that tyrosines, by virtue of their ability to form radicals, act as redox cofactors in a new pathway. The mechanism is discussed in terms of the Marcus theory and the specific protonation/deprotonation states of the oxoferryl iron and tyrosine. Tyrosine radicals have been observed and quantified by EPR spectroscopy in both mutants, consistent with the proposed mechanism. The location of each radical is unambiguous and allows us to validate theoretical methods that assign radical location on the basis of EPR hyperfine structure. Mutation to tyrosine decreases the lipid peroxidase activity of this myoglobin in the presence of low concentrations of reductant, and the possibility of decreasing the intrinsic toxicity of hemoglobin by introduction of these pathways is discussed. © 2012 American Chemical Society