Opsin expression: new mechanism for modulating colour vision

Each cone photoreceptor in the retina responds to light in a limited range of wavelengths, giving it a spectral phenotype. This phenotype is determined by the most prevalent of the photoreceptor's visual-pigment proteins (opsins) and is assumed to remain unchanged during an animal's lifetime. Here we show that in the Pacific pink salmon, Oncorhynchus gorbuscha, single cones can switch their spectral phenotype from ultraviolet to blue by regulating the production of the appropriate opsins as the fish grow older. This photoreceptor plasticity may operate to modulate colour vision as the salmon's lifestyle changes.     

A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac

With the availability of complete genome sequence for Drosophila melanogaster, one of the next strategic goals for fly researchers is a complete gene knockout collection. The P-element transposon, the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum. It has been estimated that 87% saturation of the approximately 13,500-gene complement of D. melanogaster might require generating and analyzing up to 150,000 insertions. We describe specific improvements to the lepidopteran transposon piggyBac and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5' regulatory sequences.     

The pre-raphaelites and science

Classic voltaic batteries of the silver/zinc and copper/zinc types are the ancestors of today's primary cells, and facilitated the development of many aspects of electrical technology. Nevertheless, they appear never to have been studied and evaluated in a quantitative manner, with results recorded in terms of volts, amps, ohms, and watts. Research of this nature is reported here, and has been conducted for the most part with copper/zinc cells. Log–log graphs of voltage versus load and current, and power versus load, are presented for many electrolyte systems. It has been shown that, although the textbook electrolyte of dilute sulphuric acid does work, it is an order of magnitude inferior to a solution containing some additional nitric acid. The latter diminishes the current‐limiting phenomenon of polarization, and was in fact used by Davy, Faraday, and other early investigators. A quantitative consideration of Nicholson and Carlisle's discovery of the electrolysis of water with a silver/zinc voltaic pile is followed by examination of the electrolysis of pure water, trough batteries, and Davy's isolation of potassium and sodium. Every battery gives maximum power when its resistance is adjusted (by appropriate series/parallel connections) to match the resistance of the load: the maximum output of the ‘Great Battery’ of the Royal Institution is assessed at no more than 3 kW. The paper concludes with a note on the recognized hazard of long‐term exposure to mercury vapour (produced by amalgamation of zinc electrodes in batteries) and its possible relevance to the health of Michael Faraday.     

An African origin for the intimate association between humans and Helicobacter pylori

Infection of the stomach by Helicobacter pylori is ubiquitous among humans. However, although H. pylori strains from different geographic areas are associated with clear phylogeographic differentiation, the age of an association between these bacteria with humans remains highly controversial. Here we show, using sequences from a large data set of bacterial strains that, as in humans, genetic diversity in H. pylori decreases with geographic distance from east Africa, the cradle of modern humans. We also observe similar clines of genetic isolation by distance (IBD) for both H. pylori and its human host at a worldwide scale. Like humans, simulations indicate that H. pylori seems to have spread from east Africa around 58,000 yr ago. Even at more restricted geographic scales, where IBD tends to become blurred, principal component clines in H. pylori from Europe strongly resemble the classical clines for Europeans described by Cavalli-Sforza and colleagues. Taken together, our results establish that anatomically modern humans were already infected by H. pylori before their migrations from Africa and demonstrate that H. pylori has remained intimately associated with their human host populations ever since.     

Neurovascular development and links to disease

The developing central nervous system (CNS) is vascularized via ingression of blood vessels from the outside as the neural tissue expands. This angiogenic process occurs without perturbing CNS architecture due to exquisite cross-talk between the neural compartment and invading blood vessels. Subsequently, this intimate relationship also promotes the formation of the neurovascular unit that underlies the blood–brain barrier and regulates blood flow to match brain activity. This review provides a historical perspective on research into CNS blood vessel growth and patterning, discusses current models used to study CNS angiogenesis, and provides an overview of the cellular and molecular mechanisms that promote blood vessel growth and maturation. Finally, we highlight the significance of these mechanisms for two different types of neurovascular CNS disease.     

Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration

Phosphoinositide 3-kinases (PI3Ks) signal downstream of multiple cell-surface receptor types. Class IA PI3K isoforms couple to tyrosine kinases and consist of a p110 catalytic subunit (p110alpha, p110beta or p110delta), constitutively bound to one of five distinct p85 regulatory subunits. PI3Ks have been implicated in angiogenesis, but little is known about potential selectivity among the PI3K isoforms and their mechanism of action in endothelial cells during angiogenesis in vivo. Here we show that only p110alpha activity is essential for vascular development. Ubiquitous or endothelial cell-specific inactivation of p110alpha led to embryonic lethality at mid-gestation because of severe defects in angiogenic sprouting and vascular remodelling. p110alpha exerts this critical endothelial cell-autonomous function by regulating endothelial cell migration through the small GTPase RhoA. p110alpha activity is particularly high in endothelial cells and preferentially induced by tyrosine kinase ligands (such as vascular endothelial growth factor (VEGF)-A). In contrast, p110beta in endothelial cells signals downstream of G-protein-coupled receptor (GPCR) ligands such as SDF-1alpha, whereas p110delta is expressed at low level and contributes only minimally to PI3K activity in endothelial cells. These results provide the first in vivo evidence for p110-isoform selectivity in endothelial PI3K signalling during angiogenesis.