Chromatic sensitivity of ganglion cells in the peripheral primate retina

Visual abilities change over the visual field. For example, our ability to detect movement is better in peripheral vision than in foveal vision, but colour discrimination is markedly worse. The deterioration of colour vision has been attributed to reduced colour specificity in cells of the midget, parvocellular (PC) visual pathway in the peripheral retina. We have measured the colour specificity (red-green chromatic modulation sensitivity) of PC cells at eccentricities between 20 and 50 degrees in the macaque retina. Here we show that most peripheral PC cells have red-green modulation sensitivity close to that of foveal PC cells. This result is incompatible with the view that PC pathway cells in peripheral retina make indiscriminate connections ('random wiring') with retinal circuits devoted to different spectral types of cone photoreceptors. We show that selective cone connections can be maintained by dendritic field anisotropy, consistent with the morphology of PC cell dendritic fields in peripheral retina. Our results also imply that postretinal mechanisms contribute to the psychophysically demonstrated deterioration of colour discrimination in the peripheral visual field.     

Phospholipase Cgamma1 controls surface expression of TRPC3 through an intermolecular PH domain

Many ion channels are regulated by lipids, but prominent motifs for lipid binding have not been identified in most ion channels. Recently, we reported that phospholipase Cgamma1 (PLC-gamma1) binds to and regulates TRPC3 channels, components of agonist-induced Ca2+ entry into cells. This interaction requires a domain in PLC-gamma1 that includes a partial pleckstrin homology (PH) domain-a consensus lipid-binding and protein-binding sequence. We have developed a gestalt algorithm to detect hitherto 'invisible' PH and PH-like domains, and now report that the partial PH domain of PLC-gamma1 interacts with a complementary partial PH-like domain in TRPC3 to elicit lipid binding and cell-surface expression of TRPC3. Our findings imply a far greater abundance of PH domains than previously appreciated, and suggest that intermolecular PH-like domains represent a widespread signalling mode.     

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.