Turnip mosaic potyvirus probably first spread to Eurasian brassica crops from wild orchids about 1000 years ago

Turnip mosaic potyvirus (TuMV) is probably the most widespread and damaging virus that infects cultivated brassicas worldwide. Previous work has indicated that the virus originated in western Eurasia, with all of its closest relatives being viruses of monocotyledonous plants. Here we report that we have identified a sister lineage of TuMV-like potyviruses (TuMV-OM) from European orchids. The isolates of TuMV-OM form a monophyletic sister lineage to the brassica-infecting TuMVs (TuMV-BIs), and are nested within a clade of monocotyledon-infecting viruses. Extensive host-range tests showed that all of the TuMV-OMs are biologically similar to, but distinct from, TuMV-BIs and do not readily infect brassicas. We conclude that it is more likely that TuMV evolved from a TuMV-OM-like ancestor than the reverse. We did Bayesian coalescent analyses using a combination of novel and published sequence data from four TuMV genes [helper component-proteinase protein (HC-Pro), protein 3(P3), nuclear inclusion b protein (NIb), and coat protein (CP)]. Three genes (HC-Pro, P3, and NIb), but not the CP gene, gave results indicating that the TuMV-BI viruses diverged from TuMV-OMs around 1000 years ago. Only 150 years later, the four lineages of the present global population of TuMV-BIs diverged from one another. These dates are congruent with historical records of the spread of agriculture in Western Europe. From about 1200 years ago, there was a warming of the climate, and agriculture and the human population of the region greatly increased. Farming replaced woodlands, fostering viruses and aphid vectors that could invade the crops, which included several brassica cultivars and weeds. Later, starting 500 years ago, inter-continental maritime trade probably spread the TuMV-BIs to the remainder of the world

Mapping EORTC-QLQ-C30 to EQ-5D-3L in patients with colorectal cancer

AIMS: The primary aim of this study was to perform a mapping of the EORTC-QLQ-C30 scores to EQ-5D-3L for the SIRFLOX study; a large dataset of patients with previously untreated liver-only or liver-dominant metastatic colorectal cancer (mCRC). A secondary aim was to compare the predictive validity of existing mappings from EORTC-QLQ-C30 to EQ-5D-3L conducted in other cancers. METHODS AND MATERIALS: Questionnaires (completed within 529 patients) were used in a linear mixed regression to model EQ-5D-3L utility values (scored using the UK tariff) as a function of the five function scores, nine symptom scores and the global score from the EORTC-QLQ-C30 questionnaire. A Tobit regression was also performed. The mean EQ-5D-3L values for the SIRFLOX trial were calculated and compared with predicted EQ-5D-3L values derived using published. RESULTS: The linear mixed regression model provided a satisfactory mapping between the EORTC-QLQ-C30 and the EQ-5D-3L, whilst the Tobit model did not perform as well. When utilities from the SIRFLOX data were calculated with previously published mapping studies, three out of five studies performed well (<10% mean difference). LIMITATIONS: The main limitation of the study was the lack of meaningful observations post-progression (67 paired observations). For this reason, we were unable to test whether the mapping holds by disease stage. Additionally, although the study adds to the literature of mappings to the EQ-5D-3L, it is not known how results would differ using the EQ-5D-5L. CONCLUSION: This study is the first of its kind in liver-only or liver-dominant mCRC, and mCRC in general. The mapping constructed showed a good fit to the data and provides practitioners with an additional mapping between EORTC-QLQ-C30 to EQ-5D-3L using a large dataset (529 patients, 707 paired observations). The study also confirmed the generalisability of mappings published by Proskorovsky, Kontodimopoulos and Longworth to liver-only or liver-dominant mCRC

Ocean warming, not acidification, controlled coccolithophore response during past greenhouse climate change

Current carbon dioxide emissions are an assumed threat to oceanic calcifying plankton (coccolithophores) not just due to rising sea-surface temperatures, but also because of ocean acidification (OA). This assessment is based on single species culture experiments that are now revealing complex, synergistic, and adaptive responses to such environmental change. Despite this complexity, there is still a widespread perception that coccolithophore calcification will be inhibited by OA. These plankton have an excellent fossil record, and so we can test for the impact of OA during geological carbon cycle events, providing the added advantages of exploring entire communities across real-world major climate perturbation and recovery. Here we target fossil coccolithophore groups (holococcoliths and braarudosphaerids) expected to exhibit greatest sensitivity to acidification because of their reliance on extracellular calcification. Across the Paleocene-Eocene Thermal Maximum (56 Ma) rapid warming event, the biogeography and abundance of these extracellular calcifiers shifted dramatically, disappearing entirely from low latitudes to become limited to cooler, lower saturation-state areas. By comparing these range shift data with the environmental parameters from an Earth system model, we show that the principal control on these range retractions was temperature, with survival maintained in high-latitude refugia, despite more adverse ocean chemistry conditions. Deleterious effects of OA were only evidenced when twinned with elevated temperatures

Coccolithophore calcification response to past ocean acidification and climate change

Anthropogenic carbon dioxide emissions are forcing rapid ocean chemistry changes and causing ocean acidification (OA), which is of particular significance for calcifying organisms, including planktonic coccolithophores. Detailed analysis of coccolithophore skeletons enables comparison of calcite production in modern and fossil cells in order to investigate biomineralization response of ancient coccolithophores to climate change. Here we show that the two dominant coccolithophore taxa across the Paleocene–Eocene Thermal Maximum (PETM) OA global warming event (~56 million years ago) exhibited morphological response to environmental change and both showed reduced calcification rates. However, only Coccolithus pelagicus exhibits a transient thinning of coccoliths, immediately before the PETM, that may have been OA-induced. Changing coccolith thickness may affect calcite production more significantly in the dominant modern species Emiliania huxleyi, but, overall, these PETM records indicate that the environmental factors that govern taxonomic composition and growth rate will most strongly influence coccolithophore calcification response to anthropogenic change

Assessing constancy of substitution rates in viruses over evolutionary time

<p>Abstract</p> <p>Background</p> <p>Phylogenetic analyses reveal probable patterns of divergence of present day organisms from common ancestors. The points of divergence of lineages can be dated if a corresponding historical or fossil record exists. For many species, in particular viruses, such records are rare. Recently, Bayesian phylogenetic analysis using sequences from closely related organisms isolated at different times have been used to calibrate divergences. Phylogenetic analyses depend on the assumption that the average substitution rates that can be calculated from the data apply throughout the course of evolution. </p> <p>Results</p> <p>The present study tests this crucial assumption by charting the kinds of substitutions observed between pairs of sequences with different levels of total substitutions. Datasets of aligned sequences, both viral and non-viral, were assembled. For each pair of sequences in an aligned set, the distribution of nucleotide interchanges and the total number of changes were calculated. Data were binned according to total numbers of changes and plotted. The accumulation of the six possible interchange types in retroelements as a function of distance followed closely the expected hyperbolic relationship. For other datasets, however, significant deviations from this relationship were noted. A rapid initial accumulation of transition interchanges was frequent among the datasets and anomalous changes occurred at specific divergence levels. </p> <p>Conclusions</p> <p>The accumulation profiles suggested that substantial changes in frequencies of types of substitutions occur over the course of evolution and that such changes should be considered in evaluating and dating viral phylogenies.</p

Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy. Objective: To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone. Design, Setting, and Participants: Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019. Exposure: Participants received either OAC plus AP or OAC alone. Main Outcomes and Measures: Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications. Results: A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months). Conclusions and Relevance: This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation

Algal plankton turn to hunting to survive and recover from end-Cretaceous impact darkness

The end-Cretaceous bolide impact triggered the devastation of marine ecosystems. However, the specific kill mechanism(s) are still debated, and how primary production subsequently recovered remains elusive. We used marine plankton microfossils and eco-evolutionary modeling to determine strategies for survival and recovery, finding that widespread phagotrophy (prey ingestion) was fundamental to plankton surviving the impact and also for the subsequent reestablishment of primary production. Ecological selectivity points to extreme post-impact light inhibition as the principal kill mechanism, with the marine food chain temporarily reset to a bacteria-dominated state. Subsequently, in a sunlit ocean inhabited by only rare survivor grazers but abundant small prey, it was mixotrophic nutrition (autotrophy and heterotrophy) and increasing cell sizes that enabled the eventual reestablishment of marine food webs some 2 million years later

Controlled interfacial assembly of 2D curved colloidal crystals and jammed shells

Assembly of colloidal particles on fluid interfaces is a promising technique for synthesizing two-dimensional micro-crystalline materials useful in fields as diverse as biomedicine1, materials science2, mineral flotation3 and food processing4. Current approaches rely on bulk emulsification methods, require further chemical and thermal treatments, and are restrictive with respect to the materials employed5-9. The development of methods that exploit the great potential of interfacial assembly for producing tailored materials have been hampered by the lack of understanding of the assembly process. Here we report a microfluidic method that allows direct visualization and understanding of the dynamics of colloidal crystal growth on curved interfaces. The crystals are periodically ejected to form stable jammed shells, which we refer to as colloidal armour. We propose that the energetic barriers to interfacial crystal growth and organization can be overcome by targeted delivery of colloidal particles through hydrodynamic flows. Our method allows an unprecedented degree of control over armour composition, size and stability.Comment: 18 pages, 5 figure

Detecting behavioural changes in human movement to inform the spatial scale of interventions against COVID-19

On March 23 2020, the UK enacted an intensive, nationwide lockdown to mitigate transmission of COVID-19. As restrictions began to ease, more localized interventions were used to target resurgences in transmission. Understanding the spatial scale of networks of human interaction, and how these networks change over time, is critical to targeting interventions at the most at-risk areas without unnecessarily restricting areas at low risk of resurgence. We use detailed human mobility data aggregated from Facebook users to determine how the spatially-explicit network of movements changed before and during the lockdown period, in response to the easing of restrictions, and to the introduction of locally-targeted interventions. We also apply community detection techniques to the weighted, directed network of movements to identify geographically-explicit movement communities and measure the evolution of these community structures through time. We found that the mobility network became more sparse and the number of mobility communities decreased under the national lockdown, a change that disproportionately affected long distance connections central to the mobility network. We also found that the community structure of areas in which locally-targeted interventions were implemented following epidemic resurgence did not show reorganization of community structure but did show small decreases in indicators of travel outside of local areas. We propose that communities detected using Facebook or other mobility data be used to assess the impact of spatially-targeted restrictions and may inform policymakers about the spatial extent of human movement patterns in the UK. These data are available in near real-time, allowing quantification of changes in the distribution of the population across the UK, as well as changes in travel patterns to inform our understanding of the impact of geographically-targeted interventions

The Prehistory of Potyviruses: Their Initial Radiation Was during the Dawn of Agriculture

Background: Potyviruses are found world wide, are spread by probing aphids and cause considerable crop damage. Potyvirus is one of the two largest plant virus genera and contains about 15% of all named plant virus species. When and why did the potyviruses become so numerous? Here we answer the first question and discuss the other. Methods and Findings: We have inferred the phylogenies of the partial coat protein gene sequences of about 50 potyviruses, and studied in detail the phylogenies of some using various methods and evolutionary models. Their phylogenies have been calibrated using historical isolation and outbreak events: the plum pox virus epidemic which swept through Europe in the 20th century, incursions of potyviruses into Australia after agriculture was established by European colonists, the likely transport of cowpea aphid-borne mosaic virus in cowpea seed from Africa to the Americas with the 16th century slave trade and the similar transport of papaya ringspot virus from India to the Americas. Conclusions/Significance: Our studies indicate that the partial coat protein genes of potyviruses have an evolutionary rate of about 1.1561024 nucleotide substitutions/site/year, and the initial radiation of the potyviruses occurred only about 6,600 years ago, and hence coincided with the dawn of agriculture. We discuss the ways in which agriculture may have triggered the prehistoric emergence of potyviruses and fostered their speciation