Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma.     

An electrochemical and microstructural characterization of steel-mortar admixed with corrosion inhibitors

The present research brings new insights on the role of admixed corrosion inhibitors in the processes of cement hydration and rebar corrosion.The admixing of NaCl and the corrosion inhibitors in fresh mortar was found to alter the morphology and microstructure of the hardened mortar at the steel-mortar interfacial region.The admixing of the inhibitors increased the risk of carbonation of cement hydrates at the steel-mortar interfacial region,but partially displaced chloride ions. Chloride and the admixed in...     

Different effects of synthetic delta 9-tetrahydrocannabinol and cannabis extract on steroid metabolism in male rats

Repeated oral administration of cannabis extract as well as synthetic delta9-tetrahydrocannabinol to male rats produced significant changes in excretion of androgenic steroids and their metabolites as detectable in blood and urine. Cannabis extracts were found to be significantly more active than the mixtures containing same amounts of synthetic cannabinoids.     

Laboratory detection of X-ray fringes with a grazing-incidence interferometer

Starting with Galileo's observations of the Solar System, improvements of an order of magnitude in either the sensitivity or resolution of astronomical instruments have always brought revolutionary discoveries. The X-ray band of the spectrum, where exotic objects can have extremely high surface brightness, is ideally suited for significant improvements in imaging, but progress has been impeded by a lack of optics of sufficiently high sensitivity and quality. Here we present an X-ray interferometer design that is practical for adaptation to astronomical observatories. Our prototype interferometer, having just under one millimetre of baseline, creates fringes at 1.25 keV with an angular resolution of 100 milliarcseconds. With a larger version in orbit it will be possible to resolve X-ray sources at 10(-7) arcseconds, three orders of magnitude better than the finest-resolution images ever achieved on the sky (in the radio part of the spectrum) and over one million times better than the current best X-ray images. With such resolutions, we can study the environments of pulsars, resolve and then model relativistic blast waves, image material falling into a black hole, watch the physical formation of astrophysical jets, and study the dynamos of stellar coronae.     

Ultrasensitive pheromone detection by mammalian vomeronasal neurons

The vomeronasal organ (VNO) is a chemoreceptive organ that is thought to transduce pheromones into electrical responses that regulate sexual, hormonal and reproductive function in mammals. The characteristics of pheromone signal detection by vomeronasal neurons remain unclear. Here we use a mouse VNO slice preparation to show that six putative pheromones evoke excitatory responses in single vomeronasal neurons, leading to action potential generation and elevated calcium entry. The detection threshold for some of these chemicals is remarkably low, near 10(-11) M, placing these neurons among the most sensitive chemodetectors in mammals. Using confocal calcium imaging, we map the epithelial representation of the pheromones to show that each of the ligands activates a unique, nonoverlapping subset of vomeronasal neurons located in apical zones of the epithelium. These neurons show highly selective tuning properties and their tuning curves do not broaden with increasing concentrations of ligand, unlike those of receptor neurons in the main olfactory epithelium. These findings provide a basis for understanding chemical signals that regulate mammalian communication and sexual behaviour.     

Capture rates of reptiles and amphibians on black-tailed prairie dog ( Cynomys ludovicianus ) colonies and on uncolonized prairie in Colorado

Prairie dog eradication negatively affects dependent wildlife. Assessing the effects of prairie dog activities on reptiles and amphibians may depend upon the efficacy of trapping designs. We compared capture rates of reptiles and amphibians on black-tailed prairie dog ( Cynomys ludovicianus ) colonies and on adjacent uncolonized short-grass prairie, using funnel traps and pitfall traps with drift fences, as well as ground captures. We captured 152 reptiles and amphibians representing 10 species. We captured 51.3% of all reptiles and amphibians on colonies, compared to 48.7% from uncolonized sites. Overall, captures of reptiles and amphibians were similar on colonies and uncolonized sites for all capture methods combined. We achieved higher capture rates on uncolonized sites using funnel traps and pitfall traps but higher capture rates on colonies for ground captures. For all years on all sites combined, we captured significantly more animals in funnel traps (52.6%), surpassing pitfall trap captures (23.0%) and ground captures (24.3%). We recommend using multiple Y-shaped drift fence arrays ≥7.6 m in length, funnel traps with double-ended openings, and black-colored pitfall traps with opening diameters ≥30 cm.     

Centre-surround inhibition among olfactory bulb glomeruli

Centre-surround inhibition--the suppression of activity of neighbouring cells by a central group of neurons--is a fundamental mechanism that increases contrast in patterned sensory processing. The initial stage of neural processing in olfaction occurs in olfactory bulb glomeruli, but evidence for functional interactions between glomeruli is fragmentary. Here we show that the so-called 'short axon' cells, contrary to their name, send interglomerular axons over long distances to form excitatory synapses with inhibitory periglomerular neurons up to 20-30 glomeruli away. Interglomerular excitation of these periglomerular cells potently inhibits mitral cells and forms an on-centre, off-surround circuit. This interglomerular centre-surround inhibitory network, along with the well-established mitral-granule-mitral inhibitory circuit, forms a serial, two-stage inhibitory circuit that could enhance spatiotemporal responses to odours.