A wheat kinase and immune receptor form host-specificity barriers against the blast fungus.

Since emerging in Brazil in 1985, wheat blast has spread throughout South America and recently appeared in Bangladesh and Zambia. Here we show that two wheat resistance genes, Rwt3 and Rwt4, acting as host-specificity barriers against non-Triticum blast pathotypes encode a nucleotide-binding leucine-rich repeat immune receptor and a tandem kinase, respectively. Molecular isolation of these genes will enable study of the molecular interaction between pathogen effector and host resistance genes.

Population genomic analysis of Aegilops tauschii identifies targets for bread wheat improvement.

Aegilops tauschii, the diploid wild progenitor of the D subgenome of bread wheat, is a reservoir of genetic diversity for improving bread wheat performance and environmental resilience. Here we sequenced 242 Ae. tauschii accessions and compared them to the wheat D subgenome to characterize genomic diversity. We found that a rare lineage of Ae. tauschii geographically restricted to present-day Georgia contributed to the wheat D subgenome in the independent hybridizations that gave rise to modern bread wheat. Through k-mer-based association mapping, we identified discrete genomic regions with candidate genes for disease and pest resistance and demonstrated their functional transfer into wheat by transgenesis and wide crossing, including the generation of a library of hexaploids incorporating diverse Ae. tauschii genomes. Exploiting the genomic diversity of the Ae. tauschii ancestral diploid genome permits rapid trait discovery and functional genetic validation in a hexaploid background amenable to breeding.

Pace of change in coronary heart disease mortality in Finland, Ireland and the United Kingdom from 1985 to 2006.

BACKGROUND: Finland, Ireland and the United Kingdom have the highest rates of coronary heart disease (CHD) mortality among EU-15 countries. This study examines the pace of change in CHD mortality in these countries from 1985-2006. METHODS: The percentage change in 5-year average all age, under 65 and 65 years and over age standardized mortality rates from 1985-89 to 2002-06 was calculated for each country. Joinpoint regression analysis was used to analyse age standardized mortality rates to identify points (years) where the slope of the linear trend changed significantly. The pace of change in the CHD mortality rate was measured using annual percentage change (APC). RESULTS: The percentage change in 5-year age standardized (under 65) CHD mortality rates was similar in Finland and the UK for both genders whereas in Ireland the rate of change was greater, especially for females. The percentage change in >/=65 year and all age rates was between 8.2% and 12.4% lower for Finnish males, and between 11.6% and 13% lower for Finnish females compared to their Irish and UK counterparts. There were different turning points in the downward trend in CHD mortality across the three countries varying from 1991-2003. The APC in CHD mortality after the turning point was greatest for Irish males (all age = -7.3%, under 65 = -8.2% and 65 and over = -7.1%), and Irish females (under 65 = -7.2%). CONCLUSION: We have identified differing pace of decline in three countries with similar burden of disease and successful national strategies to control CHD.

Subepicardial phase 0 block and discontinuous transmural conduction underlie right precordial ST-segment elevation by a SCN5A loss-of-function mutation.

Two mechanisms are generally proposed to explain right precordial ST-segment elevation in Brugada syndrome: 1) right ventricular (RV) subepicardial action potential shortening and/or loss of dome causing transmural dispersion of repolarization; and 2) RV conduction delay. Here we report novel mechanistic insights into ST-segment elevation associated with a Na(+) current (I(Na)) loss-of-function mutation from studies in a Dutch kindred with the COOH-terminal SCN5A variant p.Phe2004Leu. The proband, a man, experienced syncope at age 22 yr and had coved-type ST-segment elevations in ECG leads V1 and V2 and negative T waves in V2. Peak and persistent mutant I(Na) were significantly decreased. I(Na) closed-state inactivation was increased, slow inactivation accelerated, and recovery from inactivation delayed. Computer-simulated I(Na)-dependent excitation was decremental from endo- to epicardium at cycle length 1,000 ms, not at cycle length 300 ms. Propagation was discontinuous across the midmyocardial to epicardial transition region, exhibiting a long local delay due to phase 0 block. Beyond this region, axial excitatory current was provided by phase 2 (dome) of the M-cell action potentials and depended on L-type Ca(2+) current ("phase 2 conduction"). These results explain right precordial ST-segment elevation on the basis of RV transmural gradients of membrane potentials during early repolarization caused by discontinuous conduction. The late slow-upstroke action potentials at the subepicardium produce T-wave inversion in the computed ECG waveform, in line with the clinical ECG.