Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Quantifying the Functional Utility of Handaxe Symmetry: an experimental butchery approach

A series of experiments to test the relationship between Acheulean handaxe form and effectiveness for butchery and contribute to the continuing discussion regarding the factors influencing handaxe form. Using sixty handaxes, thirty fallow deer carcasses and two butchers a dataset was produced which permitted the statistical analysis of the relationship between effectiveness (measured using the proxies of time and the scorings of the butchers) and nine measures of handaxe morphology (frontal and side symmetry, weight, length, breadth, thickness, percentage of the circumference worked, degree of thinning and degree of elongation). The archived dataset comprises a time log for the use of each handaxe (derived from video footage of the experiments) which details the time taken to complete the various processes involved in the butchery of half a deer carcass, digital images of the experimental handaxe assemblage and summary spreadsheets of the data collected - i.e. time and subjective scorings - for each butcher

Glycocalyx-targeted therapy ameliorates age-related arterial dysfunction

Advanced age is accompanied by arterial dysfunction, as well as a diminished glycocalyx, which may be linked to reduced high molecular weight-hyaluronan (HMW-HA) synthesis. However, the impact of glycocalyx deterioration in age-related arterial dysfunction is unknown. We sought to determine if manipulations in glycocalyx properties would alter arterial function. Tamoxifen-induced hyaluronan synthase 2 (Has2) reduction was used to decrease glycocalyx properties. Three weeks post-tamoxifen treatment, glycocalyx thickness was lower in Has2 knockout compared to wild-type mice (P0.05). Has2 reduction phenocopies age-related arterial dysfunction, while 10 weeks of glycocalyx-targeted therapy that restores the glycocalyx also ameliorates age-related arterial dysfunction. These findings suggest that the glycocalyx may be a viable therapeutic target to ameliorate age-related arterial dysfunction

Dual client binding sites in the ATP-independent chaperone SurA

The ATP-independent chaperone SurA protects unfolded outer membrane proteins (OMPs) from aggregation in the periplasm of Gram-negative bacteria, and delivers them to the β-barrel assembly machinery (BAM) for folding into the outer membrane (OM). Precisely how SurA recognises and binds its different OMP clients remains unclear. Escherichia coli SurA comprises three domains: a core and two PPIase domains (P1 and P2). Here, by combining methyl-TROSY NMR, single-molecule Förster resonance energy transfer (smFRET), and bioinformatics analyses we show that SurA client binding is mediated by two binding hotspots in the core and P1 domains. These interactions are driven by aromatic-rich motifs in the client proteins, leading to SurA core/P1 domain rearrangements and expansion of clients from collapsed, non-native states. We demonstrate that the core domain is key to OMP expansion by SurA, and uncover a role for SurA PPIase domains in limiting the extent of expansion. The results reveal insights into SurA-OMP recognition and the mechanism of activation for an ATP-independent chaperone, and suggest a route to targeting the functions of a chaperone key to bacterial virulence and OM integrity

Confidence Intervals and Sample Size Calculations for Studies of Film-reading Performance

The relaxation of restrictions on the type of professions that can report films has resulted in radiographers and other healthcare professionals becoming increasingly involved in image interpretation in areas such as mammography, ultrasound and plain-film radiography. Little attention, however, has been given to sample size determinations concerning film-reading performance characteristics such as sensitivity, specificity and accuracy. Illustrated with hypothetical examples, this paper begins by considering standard errors and confidence intervals for performance characteristics and then discusses methods for determining sample size for studies of film-reading performance. Used appropriately, these approaches should result in studies that produce estimates of film-reading performance with adequate precision and enable investigators to optimize the sample size in their studies for the question they seek to answer