High-quality draft genome sequence of the causal agent of the current Panama disease epidemic

This is the final version. Available from the American Society for Microbiology via the DOI in this record. We present a high-quality draft genome assembly for Fusarium oxysporum f. sp. cubense tropical race 4 (Fusarium odoratissimum), assembled from PacBio reads and consisting of 15 contigs with a total assembly size of 48.59 Mb. This strain appears to belong to vegetative compatibility group complex 01213/16.Medical Research CouncilWellcome TrustBBSR

Sensitivity of projected long-term CO 2 emissions across the Shared Socioeconomic Pathways

Scenarios showing future greenhouse gas emissions are needed to estimate climate impacts and the mitigation efforts required for climate stabilization. Recently, the Shared Socioeconomic Pathways (SSPs) have been introduced to describe alternative social, economic and technical narratives, spanning a wide range of plausible futures in terms of challenges to mitigation and adaptation. Thus far the key drivers of the uncertainty in emissions projections have not been robustly disentangled. Here we assess the sensitivities of future CO 2 emissions to key drivers characterizing the SSPs. We use six state-of-the-art integrated assessment models with different structural characteristics, and study the impact of five families of parameters, related to population, income, energy efficiency, fossil fuel availability, and low-carbon energy technology development. A recently developed sensitivity analysis algorithm allows us to parsimoniously compute both the direct and interaction effects of each of these drivers on cumulative emissions. The study reveals that the SSP assumptions about energy intensity and economic growth are the most important determinants of future CO 2 emissions from energy combustion, both with and without a climate policy. Interaction terms between parameters are shown to be important determinants of the total sensitivities

Examination of the Cytotoxic and Embryotoxic Potential and Underlying Mechanisms of Next-Generation Synthetic Trioxolane and Tetraoxane Antimalarials

Semisynthetic artemisinin-based therapies are the first-line treatment for P. falciparum malaria, but next-generation synthetic drug candidates are urgently required to improve availability and respond to the emergence of artemisinin-resistant parasites. Artemisinins are embryotoxic in animal models and induce apoptosis in sensitive mammalian cells. Understanding the cytotoxic propensities of antimalarial drug candidates is crucial to their successful development and utilization. Here, we demonstrate that, similarly to the model artemisinin artesunate (ARS), a synthetic tetraoxane drug candidate (RKA182) and a trioxolane equivalent (FBEG100) induce embryotoxicity and depletion of primitive erythroblasts in a rodent model. We also show that RKA182, FBEG100 and ARS are cytotoxic toward a panel of established and primary human cell lines, with caspase-dependent apoptosis and caspase-independent necrosis underlying the induction of cell death. Although the toxic effects of RKA182 and FBEG100 proceed more rapidly and are relatively less cell-selective than that of ARS, all three compounds are shown to be dependent upon heme, iron and oxidative stress for their ability to induce cell death. However, in contrast to previously studied artemisinins, the toxicity of RKA182 and FBEG100 is shown to be independent of general chemical decomposition. Although tetraoxanes and trioxolanes have shown promise as next-generation antimalarials, the data described here indicate that adverse effects associated with artemisinins, including embryotoxicity, cannot be ruled out with these novel compounds, and a full understanding of their toxicological actions will be central to the continuing design and development of safe and effective drug candidates which could prove important in the fight against malaria

Intermediate predator naïveté and sex-skewed vulnerability predict the impact of an invasive higher predator

The spread of invasive species continues to reduce biodiversity across all regions and habitat types globally. However, invader impact prediction can be nebulous, and approaches often fail to integrate coupled direct and indirect invader effects. Here, we examine the ecological impacts of an invasive higher predator on lower trophic groups, further developing methodologies to more holistically quantify invader impact. We employ functional response (FR, resource use under different densities) and prey switching experiments to examine the trait- and density-mediated impacts of the invasive mosquitofish Gambusia affinis on an endemic intermediate predator Lovenula raynerae (Copepoda). Lovenula raynerae effectively consumed larval mosquitoes, but was naïve to mosquitofish cues, with attack rates and handling times of the intermediate predator unaffected by mosquitofish cue-treated water. Mosquitofish did not switch between male and female prey, consistently displaying a strong preference for female copepods. We thus demonstrate a lack of risk-reduction activity in the presence of invasive fish by L. raynerae and, in turn, high susceptibility of such intermediate trophic groups to invader impact. Further, we show that mosquitofish demonstrate sex-skewed predator selectivity towards intermediate predators of mosquito larvae, which may affect predator population demographics and, perversely, increase disease vector proliferations. We advocate the utility of FRs and prey switching combined to holistically quantify invasive species impact potential on native organisms at multiple trophic levels

The many possible climates from the Paris Agreement’s aim of 1.5 °C warming

The United Nations’ Paris Agreement includes the aim of pursuing efforts to limit global warming to only 1.5 °C above pre-industrial levels. However, it is not clear what the resulting climate would look like across the globe and over time. Here we show that trajectories towards a ‘1.5 °C warmer world’ may result in vastly different outcomes at regional scales, owing to variations in the pace and location of climate change and their interactions with society’s mitigation, adaptation and vulnerabilities to climate change. Pursuing policies that are considered to be consistent with the 1.5 °C aim will not completely remove the risk of global temperatures being much higher or of some regional extremes reaching dangerous levels for ecosystems and societies over the coming decades

Model uncertainties in climate change impacts on Sahel precipitation in ensembles of CMIP5 and CMIP6 simulations

The impact of climate change on Sahel precipitation suffers from large uncertainties and is strongly model-dependent. In this study, we analyse sources of inter-model spread in Sahel precipitation change by decomposing precipitation into its dynamic and thermodynamic terms, using a large set of climate model simulations. Results highlight that model uncertainty is mostly related to the response of the atmospheric circulation to climate change (dynamic changes), while thermodynamic changes are less uncertain among climate models. Uncertainties arise mainly because the models simulate different shifts in atmospheric circulation over West Africa in a warmer climate. We linked the changes in atmospheric circulation to the changes in Sea Surface Temperature, emphasising that the Northern hemispheric temperature gradient is primary to explain uncertainties in Sahel precipitation change. Sources of Sahel precipitation uncertainties are shown to be the same in the new generation of climate models (CMIP6) as in the previous generation of models (CMIP5)

Early changes in Orthopteran assemblages after grassland restoration : a comparison of space-for-time substitution versus repeated-measures monitoring

Grasslands harbour significant biodiversity and their restoration is a common intervention in biodiversity conservation. However, we know very little on how grassland restoration influences arthropod groups. Here we compared orthopteran assemblages in croplands, natural grasslands and one to four-year-old grasslands restored in a large-scale restoration on former croplands in Hortobágy National Park (E-Hungary). Sampling was done by standardized sweep-netting both in a repeated measures design and space-for-time substitution (chronosequence) design. General linear models with repeated measures from five years showed that species richness, abundance and Shannon diversity of orthopterans decreased in the year following restoration but increased afterwards. By the fourth year, species richness almost doubled and abundance increased almost ten-fold in restored grasslands compared to croplands. Multivariate analyses showed that species composition in the first two years did not progress much but by the third and fourth year there was partial overlap with natural grasslands. Local restoration conditions (last crop, seed mixture) and landscape configuration (proportion of natural grasslands < 1 km away) did not influence the above patterns in either the repeated measures or the chronosequence design, whereas time since restoration affected almost all community variables. Our results suggest that generalist ubiquitous species appeared in restored grasslands first and the more sensitive species colonized the restored fields gradually in later years. The qualitative and quantitative properties of the orthopteran assemblages in restored fields did not yet reach those of natural grasslands, therefore, our study suggests that the full regeneration of the orthopteran assemblages takes more than four years

Influence of the oxygen microenvironment on the proangiogenic potential of human endothelial colony forming cells

Therapeutic angiogenesis is a promising strategy to promote the formation of new or collateral vessels for tissue regeneration and repair. Since changes in tissue oxygen concentrations are known to stimulate numerous cell functions, these studies have focused on the oxygen microenvironment and its role on the angiogenic potential of endothelial cells. We analyzed the proangiogenic potential of human endothelial colony-forming cells (hECFCs), a highly proliferative population of circulating endothelial progenitor cells, and compared outcomes to human dermal microvascular cells (HMVECs) under oxygen tensions ranging from 1% to 21% O2, representative of ischemic or healthy tissues and standard culture conditions. Compared to HMVECs, hECFCs (1) exhibited significantly greater proliferation in both ischemic conditions and ambient air; (2) demonstrated increased migration compared to HMVECs when exposed to chemotactic gradients in reduced oxygen; and (3) exhibited comparable or superior proangiogenic potential in reduced oxygen conditions when assessed using a vessel-forming assay. These data demonstrate that the angiogenic potential of both endothelial populations is influenced by the local oxygen microenvironment. However, hECFCs exhibit a robust angiogenic potential in oxygen conditions representative of physiologic, ischemic, or ambient air conditions, and these findings suggest that hECFCs may be a superior cell source for use in cell-based approaches for the neovascularization of ischemic or engineered tissues