Increased protection from reactive oxygen species (ROS) is believed to increase life span. However, it has not been clearly demonstrated that endogenous ROS production actually limits normal life span. We have identified a mutation in the Caenorhabditis elegans iron sulfur protein (isp-1) of mitochondrial complex III, which results in low oxygen consumption, decreased sensitivity to ROS, and increased life span. Furthermore, combining isp-1(qm150) with a mutation (daf-2) that increases resistance to ROS does not result in any significant further increase in adult life span. These findings indicate that both isp-1 and daf-2 mutations increase life span by lowering oxidative stress and result in the maximum life span increase that can be produced in this way.

The mixed linear model has been widely used in genome-wide association studies (GWAS), but its application to multi-locus GWAS analysis has not been explored and assessed. Here, we implemented a fast multi-locus random-SNP-effect EMMA (FASTmrEMMA) model for GWAS. The model is built on random single nucleotide polymorphism (SNP) effects and a new algorithm. This algorithm whitens the covariance matrix of the polygenic matrix K and environmental noise, and specifies the number of nonzero eigenvalues as one. The model first chooses all putative quantitative trait nucleotides (QTNs) with ≤ 0.005 P-values and then includes them in a multi-locus model for true QTN detection. Owing to the multi-locus feature, the Bonferroni correction is replaced by a less stringent selection criterion. Results from analyses of both simulated and real data showed that FASTmrEMMA is more powerful in QTN detection and model fit, has less bias in QTN effect estimation and requires a less running time than existing single- and multi-locus methods, such as empirical Bayes, settlement of mixed linear model under progressively exclusive relationship (SUPER), efficient mixed model association (EMMA), compressed MLM (CMLM) and enriched CMLM (ECMLM). FASTmrEMMA provides an alternative for multi-locus GWAS.

Although the dog is the principal species used for in vivo studies of atrial arrhythmias, little is known about currents governing canine atrial repolarization. Cells were isolated from dog atria by exposure to collagenase of tissue in vitro ("chunk cells") and by arterial perfusion ("perfusion cells"). Whole cell voltage clamp revealed transient outward K+ current (Ito1), Ca(2+)-dependent Cl- current (Ito2), and delayed rectifier K+ current (IK). Ito1 recovered rapidly and showed little frequency dependence. Two components of IK were present as follows: a rapidly activating E-4031-sensitive current with marked inward recitification and a slower-activating E-4031-insensitive component. Ito1 and IK resembled corresponding currents previously described in human atrium. Transient outward currents were similar in chunk and perfusion cells, but IK was seen in 4% of chunk cells vs. 99% of perfusion cells (P < 0.001). Suppression of each identified current retarded canine action potential repolarization. We conclude that Ito1, Ito2, and both components of IK are present in dog atrium, IK is much more sensitive to the isolation method than Ito1 or Ito2, and the properties of two important repolarizing currents (Ito1 and IK) previously described in human atrium are similar to those in dog atrium.

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