Prospective surveillance of invasive group a streptococcal disease, Fiji, 2005-2007.

We undertook a prospective active surveillance study of invasive group A streptococcal (GAS) disease in Fiji over a 23-month period, 2005-2007. We identified 64 cases of invasive GAS disease, which represents an average annualized all-ages incidence of 9.9 cases/100,000 population per year (95% confidence interval [CI] 7.6-12.6). Rates were highest in those >65 years of age and in those <5 years, particularly in infants, for whom the incidence was 44.9/100,000 (95% CI 18.1-92.5). The case-fatality rate was 32% and was associated with increasing age and underlying coexisting disease, including diabetes and renal disease. Fifty-five of the GAS isolates underwent emm sequence typing; the types were highly diverse, with 38 different emm subtypes and no particular dominant type. Our data support the view that invasive GAS disease is common in developing countries and deserves increased public health attention

Climate Change Impacts on Irish River Flows: High Resolution Scenarios and Comparison with CORDEX and CMIP6 Ensembles

Climate change is likely to impact water quality, resource availability and riverine ecosystems. While large ensembles are available to assess future impacts (e.g., the Coupled Model Intercomparison Projects (CMIP) and/or CORDEX) many countries have developed their own high-resolution ensembles. This poses a selection problem with robust adaptation dependent on plausible ranges of change being adequately quantified. Therefore, it is important to compare projected changes from available ensembles. Here we assess future climate change impacts for 26 Irish catchments. Using a high-resolution national ensemble of climate models projected impacts in mean, low and high flows are assessed and uncertainties in future projections related to catchment size. We then compare future impacts from CORDEX and CMIP6 ensembles for a subset of catchments. Results suggest increases in winter flows (-3.29 to 59.63%), with wide ranges of change simulated for summer (-59.18 to 31.23%), low (-49.30 to 22.37%) and food (-19.31 to 116.34%) flows across catchments under RCP8.5 by the 2080s. These changes would challenge water management without adaptation. Smaller catchments tend to show the most extreme impacts and widest ranges of change in summer, low and food flow changes. Both the ensemble mean and range of changes from the national ensemble were more modest and narrower than the CMIP6 and CORDEX ensembles, especially for summer mean and low flows, highlighting the importance of evaluating impacts across ensembles to ensure adaptation decisions are informed by plausible ranges of change

Climate, conflict and forced migration

Despite the lack of robust empirical evidence, a growing number of media reports attempt to link climate change to the ongoing violent conflicts in Syria and other parts of the world, as well as to the migration crisis in Europe. Exploiting bilateral data on asylum seeking applications for 157 countries over the period 2006–2015, we assess the determinants of refugee flows using a gravity model which accounts for endogenous selection in order to examine the causal link between climate, conflict and forced migration. Our results indicate that climatic conditions, by affecting drought severity and the likelihood of armed conflict, played a significant role as an explanatory factor for asylum seeking in the period 2011–2015. The effect of climate on conflict occurrence is particularly relevant for countries in Western Asia in the period 2010–2012 during when many countries were undergoing political transformation. This finding suggests that the impact of climate on conflict and asylum seeking flows is limited to specific time period and contexts

Status of research and development of vaccines for Streptococcus pyogenes.

Streptococcus pyogenes is an important global pathogen, causing considerable morbidity and mortality, especially in low and middle income countries where rheumatic heart disease and invasive infections are common. There is a number of promising vaccine candidates, most notably those based on the M protein, the key virulence factor for the bacterium. Vaccines against Streptococcus pyogenes are considered as impeded vaccines because of a number of crucial barriers to development. Considerable effort is needed by key players to bring current vaccine candidates through phase III clinical trials and there is a clear need to develop a roadmap for future development of current and new candidates

Motor domain phosphorylation increases nucleotide exchange and turns MYO6 into a faster and stronger motor

Myosin motors perform many fundamental functions in eukaryotic cells by providing force generation, transport or tethering capacity. Motor activity control within the cell involves on/off switches, however, few examples are known of how myosins regulate speed or processivity and fine-tune their activity to a specific cellular task. Here, we describe a phosphorylation event for myosins of class VI (MYO6) in the motor domain, which accelerates its ATPase activity leading to a 4-fold increase in motor speed determined by actin-gliding assays, single molecule mechanics and stopped flow kinetics. We demonstrate that the serine/threonine kinase DYRK2 phosphorylates MYO6 at S267 in vitro. Single-molecule optical-tweezers studies at low load reveal that S267-phosphorylation results in faster nucleotide-exchange kinetics without change in the working stroke of the motor. The selective increase in stiffness of the acto-MYO6 complex when proceeding load-dependently into the nucleotide-free rigor state demonstrates that S267-phosphorylation turns MYO6 into a stronger motor. Finally, molecular dynamic simulations of the nucleotide-free motor reveal an alternative interaction network within insert-1 upon phosphorylation, suggesting a molecular mechanism, which regulates insert-1 positioning, turning the S267-phosphorylated MYO6 into a faster motor

Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus

Vector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverse Anopheles genomes. Here, we use a population genomic approach to investigate the basis of pirimiphos-methyl resistance in the major malaria vectors Anopheles gambiae and A. coluzzii. A combination of copy number variation and a single non-synonymous substitution in the acetylcholinesterase gene, Ace1, provides the key resistance diagnostic in an A. coluzzii population from Coˆte d’Ivoire that we used for sequence-based association mapping, with replication in other West African populations. The Ace1 substitution and duplications occur on a unique resistance haplotype that evolved in A. gambiae and introgressed into A. coluzzii, and is now common in West Africa primarily due to selection imposed by other organophosphate or carbamate insecticides. Our findings highlight the predictive value of this complex resistance haplotype for phenotypic resistance and clarify its evolutionary history, providing tools to for molecular surveillance of the current and future effectiveness of pirimiphos-methyl based interventions