Whole-genome analysis of diverse Chlamydia trachomatis strains identifies phylogenetic relationships masked by current clinical typing

Chlamydia trachomatis is responsible for both trachoma and sexually transmitted infections, causing substantial morbidity and economic cost globally. Despite this, our knowledge of its population and evolutionary genetics is limited. Here we present a detailed phylogeny based on whole-genome sequencing of representative strains of C. trachomatis from both trachoma and lymphogranuloma venereum (LGV) biovars from temporally and geographically diverse sources. Our analysis shows that predicting phylogenetic structure using ompA, which is traditionally used to classify Chlamydia, is misleading because extensive recombination in this region masks any true relationships present. We show that in many instances, ompA is a chimera that can be exchanged in part or as a whole both within and between biovars. We also provide evidence for exchange of, and recombination within, the cryptic plasmid, which is another key diagnostic target. We used our phylogenetic framework to show how genetic exchange has manifested itself in ocular, urogenital and LGV C. trachomatis strains, including the epidemic LGV serotype L2b.     

Newly identified loci that influence lipid concentrations and risk of coronary artery disease

To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.     

Effects of beta-hydroxybutyrate on rat embryos grown in culture

In order to investigate further the relationship between maternal diabetes and fetal malformation, rat embryos were grown in vitro in the presence of beta-hydroxybutyrate, one of the ketone bodies produced by diabetics. At 10 mM, beta-hydroxybutyrate produced minor abnormalities and at 20 mM it produced major abnormalities in rat embryos.     

Long-distance intraretinal connections in birds

Electrophysiological experiments have shown in both birds and mammals that remote parts of the retina, several millimetres apart, interact at the retinal level. The anatomical basis of this is poorly understood, although in mammals some cells in the ganglion cell layer have axons that terminate in the inner plexiform layer several millimetres from the cell body. In birds, the longest previously reported intraretinal connections were from amacrine cells, extending only a few hundred microns. But we here describe very long connections that span almost the entire extent of the retina in chicks and chick embryos. The parent cell bodies are in the inner nuclear layer of the ventral half of the retina, and they project in topographical order onto the dorsal half. They do not project to the brain. They may be involved in selective switching of attention between the upper and lower parts of the visual field, at an unprecedentedly early stage of visual processing.