Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design

Virus capsids are primed for disassembly, yet capsid integrity is key to generating a protective immune response. Foot-and-mouth disease virus (FMDV) capsids comprise identical pentameric protein subunits held together by tenuous noncovalent interactions and are often unstable. Chemically inactivated or recombinant empty capsids, which could form the basis of future vaccines, are even less stable than live virus. Here we devised a computational method to assess the relative stability of protein-protein interfaces and used it to design improved candidate vaccines for two poorly stable, but globally important, serotypes of FMDV: O and SAT2. We used a restrained molecular dynamics strategy to rank mutations predicted to strengthen the pentamer interfaces and applied the results to produce stabilized capsids. Structural analyses and stability assays confirmed the predictions, and vaccinated animals generated improved neutralizing-antibody responses to stabilized particles compared to parental viruses and wild-type capsids.

The status and challenge of global fire modelling

Biomass burning impacts vegetation dynamics, biogeochemical cycling, atmospheric chemistry, and climate, with sometimes deleterious socio-economic impacts. Under future climate projections it is often expected that the risk of wildfires will increase. Our ability to predict the magnitude and geographic pattern of future fire impacts rests on our ability to model fire regimes, either using well-founded empirical relationships or process-based models with good predictive skill. A large variety of models exist today and it is still unclear which type of model or degree of complexity is required to model fire adequately at regional to global scales. This is the central question underpinning the creation of the Fire Model Intercomparison Project - FireMIP, an international project to compare and evaluate existing global fire models against benchmark data sets for present-day and historical conditions. In this paper we summarise the current state-of-the-art in fire regime modelling and model evaluation, and outline what essons may be learned from FireMIP.

The Climate-system Historical Forecast Project: do stratosphere-resolving models make better seasonal climate predictions in boreal winter?

Using an international, multi-model suite of historical forecasts from the World Climate Research Programme (WCRP) Climate-system Historical Forecast Project (CHFP), we compare the seasonal prediction skill in boreal wintertime between models that resolve the stratosphere and its dynamics (“high-top”) and models that do not (“low-top”). We evaluate hindcasts that are initialized in November, and examine the model biases in the stratosphere and how they relate to boreal wintertime (Dec-Mar) seasonal forecast skill. We are unable to detect more skill in the high-top ensemble-mean than the low-top ensemble-mean in forecasting the wintertime North Atlantic Oscillation, but model performance varies widely. Increasing the ensemble size clearly increases the skill for a given model. We then examine two major processes involving stratosphere-troposphere interactions (the El Ni��o-Southern Oscillation/ENSO and the Quasi-biennial Oscillation/QBO) and how they relate to predictive skill on intra-seasonal to seasonal timescales, particularly over the North Atlantic and Eurasia regions. High-top models tend to have a more realistic stratospheric response to El Ni��o and the QBO compared to low-top models. Enhanced conditional wintertime skill over high-latitudes and the North Atlantic region during winters with El Ni��o conditions suggests a possible role for a stratospheric pathway.

Can milk proteins be a useful tool in the management of cardiometabolic health? An updated review of human intervention trials

The prevalence of cardiometabolic diseases is a significant public health burden worldwide. Emerging evidence supports the inverse association between greater dairy consumption and reduced risk of cardiometabolic diseases. Dairy proteins may have in important role in the favourable impact of dairy on human health such as blood pressure (BP) control, blood lipid and glucose control. The purpose of this review is to update and critically evaluate the evidence on the impacts of casein and whey protein in relation to metabolic function. Evidence from acute clinical studies assessing postprandial responses to milk protein ingestion suggests benefits on vascular function independent of BP, as well as improvement in glycaemic homeostasis. Chronic interventions have been less conclusive, with some showing benefits and others indicating a lack of improvement in vascular function. During chronic consumption BP appears to be lowered and both dyslipidaemia and hyperglacaemia seems to be controlled. Limited number of trials investigated the effects of dairy proteins on oxidative stress and inflammation. The beneficial changes in cardiometabolic homeostasis are likely mediated through improvements in insulin resistance, however to gain more detailed understanding on the underlying mechanism of milk proteins warrants further research. The incorporation of meals enriched with dairy protein in the habitual diet may result in the beneficial effects on cardiometabolic health. Nevertheless, future well-designed, controlled studies are needed to investigate the relative effects of both casein and whey protein on BP, vascular function, glucose homeostasis and inflammation.