Donor origin of the in vitro hematopoietic microenvironment after marrow transplantation in mice

Summary Bone marrow stroma from radiochimeric mice was established in culture. The polymorphic enzyme glucose phosphate isomerase (GPI) was used to determine the proportions of donor and recipient present in the original bone marrow and in cultured stroma. Bone marrow initially containing 95% donor GPI, when cultured and subsequently passaged for up to 8 weeks remained about 70% donor GPI. We conclude that many cultured stromal cells are donor derived in our radiochimeras and these are probably of hematopoietic origin.     

The mechanism of Z alpha 1-antitrypsin accumulation in the liver.

Most northern Europeans have only the normal M form of the plasma protease inhibitor alpha 1-antitrypsin, but some 4% are heterozygotes for the Z deficiency variant. For reasons that have not been well-understood, the Z mutation results in a blockage in the final stage of processing of antitrypsin in the liver such that in the Z homozygote only 15% of the protein is secreted into the plasma. The 85% of the alpha 1-antitrypsin that is not secreted accumulates in the endoplasmic reticulum of the hepatocyte; much of it is degraded but the remainder aggregates to form insoluble intracellular inclusions. These inclusions are associated with hepatocellular damage, and 10% of newborn Z homozygotes develop liver disease which often leads to a fatal childhood cirrhosis. Here we demonstrate the molecular pathology underlying this accumulation and describe how the Z mutation in antitrypsin results in a unique molecular interaction between the reactive centre loop of one molecule and the gap in the A-sheet of another. This loop-sheet polymerization of Z antitrypsin occurs spontaneously at 37 degrees C and is completely blocked by the insertion of a specific peptide into the A-sheet of the antitrypsin molecule. Z antitrypsin polymerized in vitro has identical properties and ultrastructure to the inclusions isolated from hepatocytes of a Z homozygote. The concentration and temperature dependence of this loop-sheet polymerization has implications for the management of the liver disease of the newborn Z homozygote.     

A photometric redshift of z = 6.39 +/- 0.12 for GRB 050904

Gamma-ray bursts (GRBs) and their afterglows are the most brilliant transient events in the Universe. Both the bursts themselves and their afterglows have been predicted to be visible out to redshifts of z approximately 20, and therefore to be powerful probes of the early Universe. The burst GRB 000131, at z = 4.50, was hitherto the most distant such event identified. Here we report the discovery of the bright near-infrared afterglow of GRB 050904 (ref. 4). From our measurements of the near-infrared afterglow, and our failure to detect the optical afterglow, we determine the photometric redshift of the burst to be z = 6.39 - 0.12 + 0.11 (refs 5-7). Subsequently, it was measured spectroscopically to be z = 6.29 +/- 0.01, in agreement with our photometric estimate. These results demonstrate that GRBs can be used to trace the star formation, metallicity, and reionization histories of the early Universe.     

Spectroscopic confirmation of a galaxy at redshift z = 8.6

Galaxies had their most significant impact on the Universe when they assembled their first generations of stars. Energetic photons emitted by young, massive stars in primeval galaxies ionized the intergalactic medium surrounding their host galaxies, cleared sightlines along which the light of the young galaxies could escape, and fundamentally altered the physical state of the intergalactic gas in the Universe continuously until the present day. Observations of the cosmic microwave background, and of galaxies and quasars at the highest redshifts, suggest that the Universe was reionized through a complex process that was completed about a billion years after the Big Bang, by redshift z?≈?6. Detecting ionizing Lyman-α photons from increasingly distant galaxies places important constraints on the timing, location and nature of the sources responsible for reionization. Here we report the detection of Lyα photons emitted less than 600?million years after the Big Bang. UDFy-38135539 (ref. 5) is at a redshift of z = 8.5549?±?0.0002, which is greater than those of the previously known most distant objects, at z = 8.2 (refs 6 and 7) and z = 6.96 (ref. 8). We find that this single source is unlikely to provide enough photons to ionize the volume necessary for the emission line to escape, requiring a significant contribution from other, probably fainter galaxies nearby.