Retinoic acid coordinates somitogenesis and left-right patterning in vertebrate embryos

A striking feature of the body plan of a majority of animals is bilateral symmetry. Almost nothing is known about the mechanisms controlling the symmetrical arrangement of the left and right body sides during development. Here we report that blocking the production of retinoic acid (RA) in chicken embryos leads to a desynchronization of somite formation between the two embryonic sides, demonstrated by a shortened left segmented region. This defect is linked to a loss of coordination of the segmentation clock oscillations. The lateralization of this defect led us to investigate the relation between somitogenesis and the left-right asymmetry machinery in RA-deficient embryos. Reversal of the situs in chick or mouse embryos lacking RA results in a reversal of the somitogenesis laterality defect. Our data indicate that RA is important in buffering the lateralizing influence of the left-right machinery, thus permitting synchronization of the development of the two embryonic sides.     

Measurement of femtometre-scale atomic displacements by X-ray absorption spectroscopy

The frequencies of extended X-ray absorption fine-structure (EXAFS) measurements, which are oscillations occurring on the high-energy side of an X-ray absorption edge, can be used to identify interatomic distances in materials. We have used a dispersive X-ray spectrometer, which has no moving components, to make rapid measurements with minimal energy drift of the difference in EXAFS from the Fe K edge in an iron-cobalt thin film undergoing periodic strain through magnetostriction. We show that magnetostriction can be detected by differential X-ray absorption. The magnitude of the recorded signal relative to the noise shows a sensitivity to mean differential atomic motion of one femtometre: a factor of 100 times more sensitive than that normally available.     

Global estimate of aerosol direct radiative forcing from satellite measurements

Atmospheric aerosols cause scattering and absorption of incoming solar radiation. Additional anthropogenic aerosols released into the atmosphere thus exert a direct radiative forcing on the climate system. The degree of present-day aerosol forcing is estimated from global models that incorporate a representation of the aerosol cycles. Although the models are compared and validated against observations, these estimates remain uncertain. Previous satellite measurements of the direct effect of aerosols contained limited information about aerosol type, and were confined to oceans only. Here we use state-of-the-art satellite-based measurements of aerosols and surface wind speed to estimate the clear-sky direct radiative forcing for 2002, incorporating measurements over land and ocean. We use a Monte Carlo approach to account for uncertainties in aerosol measurements and in the algorithm used. Probability density functions obtained for the direct radiative forcing at the top of the atmosphere give a clear-sky, global, annual average of -1.9 W m(-2) with standard deviation, +/- 0.3 W m(-2). These results suggest that present-day direct radiative forcing is stronger than present model estimates, implying future atmospheric warming greater than is presently predicted, as aerosol emissions continue to decline.     

Pharmaco-metabonomic phenotyping and personalized drug treatment

There is a clear case for drug treatments to be selected according to the characteristics of an individual patient, in order to improve efficacy and reduce the number and severity of adverse drug reactions. However, such personalization of drug treatments requires the ability to predict how different individuals will respond to a particular drug/dose combination. After initial optimism, there is increasing recognition of the limitations of the pharmacogenomic approach, which does not take account of important environmental influences on drug absorption, distribution, metabolism and excretion. For instance, a major factor underlying inter-individual variation in drug effects is variation in metabolic phenotype, which is influenced not only by genotype but also by environmental factors such as nutritional status, the gut microbiota, age, disease and the co- or pre-administration of other drugs. Thus, although genetic variation is clearly important, it seems unlikely that personalized drug therapy will be enabled for a wide range of major diseases using genomic knowledge alone. Here we describe an alternative and conceptually new 'pharmaco-metabonomic' approach to personalizing drug treatment, which uses a combination of pre-dose metabolite profiling and chemometrics to model and predict the responses of individual subjects. We provide proof-of-principle for this new approach, which is sensitive to both genetic and environmental influences, with a study of paracetamol (acetaminophen) administered to rats. We show pre-dose prediction of an aspect of the urinary drug metabolite profile and an association between pre-dose urinary composition and the extent of liver damage sustained after paracetamol administration.     

Developing space weathering on the asteroid 25143 Itokawa

Puzzlingly, the parent bodies of ordinary chondrites (the most abundant type of meteorites) do not seem to be abundant among asteroids. One possible explanation is that surfaces of the parent bodies become optically altered, to become the S-type asteroids which are abundant in the main asteroid belt. The process is called 'space weathering'-it makes the visible and near-infrared reflectance spectrum of a body darker and redder. A recent survey of small, near-Earth asteroids suggests that the surfaces of small S asteroids may have developing stages of space weathering. Here we report that a dark region on a small (550-metre) asteroid-25143 Itokawa-is significantly more space-weathered than a nearby bright region. Spectra of both regions are consistent with those of LL5-6 chondrites after continuum removal. A simple calculation suggests that the dark area has a shorter mean optical path length and about 0.04 per cent by volume more nanophase metallic iron particles than the bright area. This clearly shows that space-weathered materials accumulate on small asteroids, which are likely to be the parent bodies of LL chondrites. We conclude that, because LL meteorites are the least abundant of ordinary (H, L, and LL) chondrites, there must be many asteroids with ordinary-chondrite compositions in near-Earth orbits.     

Solving surface plasmon resonances and near field in metallic nanostructures: Green’s matrix method and its applications

With the development of nanotechnology, many new optical phenomena in nanoscale have been demonstrated. Through the coupling of optical waves and collective oscillations of free electrons in metallic nanostructures, surface plasmon polaritons can be excited accompanying a strong near field enhancement that decays in a subwavelength scale, which have potential applications in the surface-enhanced Raman scattering, biosensor, optical communication, solar cells, and nonlinear optical frequency mixing. In the present article, we review the Green’s matrix method for solving the surface plasmon resonances and near field in arbitrarily shaped nanostructures and in binary metallic nanostructures. Using this method, we design the plasmonic nanostructures whose resonances are tunable from the visible to near-infrared, study the interplay of plasmon resonances, and propose a new way to control plasmonic resonances in binary metallic nanostructures.     

Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis

The ability to cross host barriers is an essential virulence determinant of invasive microbial pathogens. Listeria monocytogenes is a model microorganism that crosses human intestinal and placental barriers, and causes severe maternofetal infections by an unknown mechanism. Several studies have helped to characterize the bacterial invasion proteins InlA and InlB. However, their respective species specificity has complicated investigations on their in vivo role. Here we describe two novel and complementary animal models for human listeriosis: the gerbil, a natural host for L. monocytogenes, and a knock-in mouse line ubiquitously expressing humanized E-cadherin. Using these two models, we uncover the essential and interdependent roles of InlA and InlB in fetoplacental listeriosis, and thereby decipher the molecular mechanism underlying the ability of a microbe to target and cross the placental barrier.     

Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24

Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer.