Early history of Earth's crust-mantle system inferred from hafnium isotopes in chondrites

The 176Lu to 176Hf decay series has been widely used to understand the nature of Earth's early crust-mantle system. The interpretation, however, of Lu-Hf isotope data requires accurate knowledge of the radioactive decay constant of 176Lu (lambda176Lu), as well as bulk-Earth reference parameters. A recent calibration of the lambda176Lu value calls for the presence of highly unradiogenic hafnium in terrestrial zircons with ages greater than 3.9 Gyr, implying widespread continental crust extraction from an isotopically enriched mantle source more than 4.3 Gyr ago, but does not provide evidence for a complementary depleted mantle reservoir. Here we report Lu-Hf isotope measurements of different Solar System objects including chondrites and basaltic eucrites. The chondrites define a Lu-Hf isochron with an initial 176Hf/177Hf ratio of 0.279628 +/- 0.000047, corresponding to lambda176Lu = 1.983 +/- 0.033 x 10-11 yr-1 using an age of 4.56 Gyr for the chondrite-forming event. This lambda176Lu value indicates that Earth's oldest minerals were derived from melts of a mantle source with a time-integrated history of depletion rather than enrichment. The depletion event must have occurred no later than 320 Myr after planetary accretion, consistent with timing inferred from extinct radionuclides.     

Accumulation of 2-μm latex particles in mouse Peyer's patches during chronic latex feeding

Summary 2-m latex particles accumulated in macrophages in intestinal Peyer's patches of mice given latex suspensions as drinking fluid for 2 months. The number of particles accumulating was a direct (but nonlinear) function of the number ingested. Some of the latex particles were still present in Peyer's patches 6 weeks after the cessation of latex feeding.Acknowledgments. Research supported by the U. S. Energy Research and Development Administration. We thank Mr W. Marin, Division of Photography and Graphic Arts, Brookhaven National Laboratory, for figure 2.The research described in this report involved animals maintained in animal care facilities fully accredited by the American Association for Accreditation of Laboratory Animal Care.     

Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation

We used resequencing and genotyping in African Americans with sickle cell anemia (SCA) to characterize associations with fetal hemoglobin (HbF) levels at the BCL11A, HBS1L-MYB and β-globin loci. Fine-mapping of HbF association signals at these loci confirmed seven SNPs with independent effects and increased the explained heritable variation in HbF levels from 38.6% to 49.5%. We also identified rare missense variants that causally implicate MYB in HbF production.     

A common variant of HMGA2 is associated with adult and childhood height in the general population

Human height is a classic, highly heritable quantitative trait. To begin to identify genetic variants influencing height, we examined genome-wide association data from 4,921 individuals. Common variants in the HMGA2 oncogene, exemplified by rs1042725, were associated with height (P = 4 x 10(-8)). HMGA2 is also a strong biological candidate for height, as rare, severe mutations in this gene alter body size in mice and humans, so we tested rs1042725 in additional samples. We confirmed the association in 19,064 adults from four further studies (P = 3 x 10(-11), overall P = 4 x 10(-16), including the genome-wide association data). We also observed the association in children (P = 1 x 10(-6), N = 6,827) and a tall/short case-control study (P = 4 x 10(-6), N = 3,207). We estimate that rs1042725 explains approximately 0.3% of population variation in height (approximately 0.4 cm increased adult height per C allele). There are few examples of common genetic variants reproducibly associated with human quantitativetraits; these results represent, to our knowledge, the first consistently replicated association with adult and childhood height.     

The role of HLA-G in immunity and hematopoiesis

The non-classical HLA class I molecule HLA-G was initially shown to play a major role in feto–maternal tolerance. Since this discovery, it has been established that HLA-G is a tolerogenic molecule which participates to the control of the immune response. In this review, we summarize the recent advances on (1) the multiple structures of HLA-G, which are closely associated with their role in the inhibition of NK cell cytotoxicity, (2) the factors that regulate the expression of HLA-G and its receptors, (3) the mechanism of action of HLA-G at the immunological synapse and through trogocytosis, and (4) the generation of suppressive cells through HLA-G. Moreover, we also review recent findings on the non-immunological functions of HLA-G in erythropoiesis and angiogenesis.     

Inhibition of human Vγ9Vδ2 T-cell antitumoral activity through HLA-G: implications for immunotherapy of cancer

Vγ9Vδ2 T cells play a crucial role in the antitumoral immune response through cytokine production and cytotoxicity. Although the expression of the immunomodulatory molecule HLA-G has been found in diverse tumors, its impact on Vγ9Vδ2 T-cell functions remains unknown. Here we showed that soluble HLA-G inhibits Vγ9Vδ2 T-cell proliferation without inducing apoptosis. Moreover, soluble HLA-G inhibited the Vγ9Vδ2 T-cell production of IFN-γ induced by phosphoantigen stimulation. The reduction in Vγ9Vδ2 T-cell IFN-γ production was also induced by membrane-bound or soluble HLA-G expressed by tumor cell lines. Finally, primary tumor cells inhibited Vγ9Vδ2 T-cell proliferation and IFN-γ production through HLA-G. In this context, HLA-G impaired Vγ9Vδ2 T-cell cytotoxicity by interacting with ILT2 inhibitory receptor. These data demonstrate that HLA-G inhibits the anti-tumoral functions of Vγ9Vδ2 T cells and imply that treatments targeting HLA-G could optimize Vγ9Vδ2 T-cell-mediated immunotherapy of cancer.     

Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN

Human vision starts with the activation of rod photoreceptors in dim light and short (S)-, medium (M)-, and long (L)- wavelength-sensitive cone photoreceptors in daylight. Recently a parallel, non-rod, non-cone photoreceptive pathway, arising from a population of retinal ganglion cells, was discovered in nocturnal rodents. These ganglion cells express the putative photopigment melanopsin and by signalling gross changes in light intensity serve the subconscious, 'non-image-forming' functions of circadian photoentrainment and pupil constriction. Here we show an anatomically distinct population of 'giant', melanopsin-expressing ganglion cells in the primate retina that, in addition to being intrinsically photosensitive, are strongly activated by rods and cones, and display a rare, S-Off, (L + M)-On type of colour-opponent receptive field. The intrinsic, rod and (L + M) cone-derived light responses combine in these giant cells to signal irradiance over the full dynamic range of human vision. In accordance with cone-based colour opponency, the giant cells project to the lateral geniculate nucleus, the thalamic relay to primary visual cortex. Thus, in the diurnal trichromatic primate, 'non-image-forming' and conventional 'image-forming' retinal pathways are merged, and the melanopsin-based signal might contribute to conscious visual perception.     

Early planetesimal melting from an age of 4.5662 Gyr for differentiated meteorites

Long- and short-lived radioactive isotopes and their daughter products in meteorites are chronometers that can test models for Solar System formation. Differentiated meteorites come from parent bodies that were once molten and separated into metal cores and silicate mantles. Mineral ages for these meteorites, however, are typically younger than age constraints for planetesimal differentiation. Such young ages indicate that the energy required to melt their parent bodies could not have come from the most likely heat source-radioactive decay of short-lived nuclides ((26)Al and (60)Fe) injected from a nearby supernova-because these would have largely decayed by the time of melting. Here we report an age of 4.5662 +/- 0.0001 billion years (based on Pb-Pb dating) for basaltic angrites, which is only 1 Myr younger than the currently accepted minimum age of the Solar System and corresponds to a time when (26)Al and (60)Fe decay could have triggered planetesimal melting. Small (26)Mg excesses in bulk angrite samples confirm that (26)Al decay contributed to the melting of their parent body. These results indicate that the accretion of differentiated planetesimals pre-dated that of undifferentiated planetesimals, and reveals the minimum Solar System age to be 4.5695 +/- 0.0002 billion years.     

An integrated view of the chemistry and mineralogy of martian soils

The mineralogical and elemental compositions of the martian soil are indicators of chemical and physical weathering processes. Using data from the Mars Exploration Rovers, we show that bright dust deposits on opposite sides of the planet are part of a global unit and not dominated by the composition of local rocks. Dark soil deposits at both sites have similar basaltic mineralogies, and could reflect either a global component or the general similarity in the compositions of the rocks from which they were derived. Increased levels of bromine are consistent with mobilization of soluble salts by thin films of liquid water, but the presence of olivine in analysed soil samples indicates that the extent of aqueous alteration of soils has been limited. Nickel abundances are enhanced at the immediate surface and indicate that the upper few millimetres of soil could contain up to one per cent meteoritic material.