Model for signal sequence recognition from amino-acid sequence of 54K subunit of signal recognition particle

Protein targeting to the endoplasmic reticulum in mammalian cells is catalysed by signal recognition particle (SRP). Cross-linking experiments have shown that the subunit of relative molecular mass 54,000 (Mr 54K; SRP54) interacts directly with signal sequences as they emerge from the ribosome. Here we present the sequence of a complementary DNA clone of SRP54 which predicts a protein that contains a putative GTP-binding domain and an unusually methionine-rich domain. The properties of this latter domain suggest that it contains the signal sequence binding site. A previously uncharacterized Escherichia coli protein has strong homology to both domains. Closely homologous GTP-binding domains are also found in the alpha-subunit of the SRP receptor (SR alpha, docking protein) in the endoplasmic reticulum membrane and in a second E. coli protein, ftsY, which resembles SR alpha. Recent work has shown that SR alpha is a GTP-binding protein and that GTP is required for the release of SRP from the signal sequence and the ribosome on targeting to the endoplasmic reticulum membrane. We propose that SRP54 and SR alpha use GTP in sequential steps of the targeting reaction and that essential features of such a pathway are conserved from bacteria to mammals.     

The afterglow of GRB 050709 and the nature of the short-hard gamma-ray bursts

The final chapter in the long-standing mystery of the gamma-ray bursts (GRBs) centres on the origin of the short-hard class of bursts, which are suspected on theoretical grounds to result from the coalescence of neutron-star or black-hole binary systems. Numerous searches for the afterglows of short-hard bursts have been made, galvanized by the revolution in our understanding of long-duration GRBs that followed the discovery in 1997 of their broadband (X-ray, optical and radio) afterglow emission. Here we present the discovery of the X-ray afterglow of a short-hard burst, GRB 050709, whose accurate position allows us to associate it unambiguously with a star-forming galaxy at redshift z = 0.160, and whose optical lightcurve definitively excludes a supernova association. Together with results from three other recent short-hard bursts, this suggests that short-hard bursts release much less energy than the long-duration GRBs. Models requiring young stellar populations, such as magnetars and collapsars, are ruled out, while coalescing degenerate binaries remain the most promising progenitor candidates.     

Major contribution of codominant CD8 and CD4 T cell epitopes to the human cytomegalovirus-specific T cell repertoire

Human cytomegalovirus (HCMV) infection or reactivation is a cause of morbidity and mortality in immunocompromised individuals. In immunocompetent individuals, in contrast, HCMV is successfully controlled by specific CD8 and CD4 T cells. Knowledge of CD8 and CD4 T cell epitopes from HCMV and their immunodominant features is crucial for the generation of epitope-specific T cells for adoptive immunotherapy and for the development of a peptide-based HCMV vaccine. Therefore, we investigated the natural frequencies of a large number of CD8 and CD4 T cell epitopes, including 10 novel ones. We determined several epitopes as immunodominant. Surprisingly, no clear hierarchies were found for CD8 T cell epitopes, indicating codominance. These results will be valuable for adoptive transfer strategies and support initiatives towards development of a peptide-based HCMV vaccine.Received 12 August 2004; received after revision 24 September 2004; accepted 29 October 2004 These authors contributed equally to this work.     

Cis-active control of mouse beta-galactosidase biosynthesis by a systemic regulatory locus.

Several higher organisms have been reported in which enzyme levels are determined genetically by sites located in close proximity to the corresponding structural genes. In several cases, these sites have been shown to act by controlling the rates of enzyme synthesis. Cis compared with trans action has been tested for those proximate regulatory sites controlling enzymes for which appropriate structural variants exist. The rate of synthesis of beta-galactosidase in mouse tissues is under the control of a regulatory locus; Bgl-s, that is tightly linked to the enzyme structural gene; we have tested the cis/trans nature of Bgl-s action by analysis of the electrophoretic mobility of the enzyme from animals heterozygous for the appropriate regulatory and structural alleles. Our results indicate that Bgl-s acts cis, controlling the expression of the structural gene located on the same chromosome.     

Zur Kinematik der Planetenbewegung in Copernicus' Commentariolus

Zusammenfassung Copernicus versucht, die Ptolemäischen Konstruktionen auf konzentrische Kreise und Epizykel zu reduzieren und aus ihnen ein wirklich einheitliches System zu schaffen. Bei der Umordnung, die er dazu vornimmt, bemüht er sich aber, so viel wie möglich vom Ptolemäischen System zu erhalten. Das punctum aequans ersetzt er bei den äußeren Planeten durch eine Näherungskonstruktion mit Hilfe eines Epizykels. Im Fall des Ptolemäischen Deferenten der Venus, der nach seinen Vorstellungen die Erdbahn wiedergibt, muß er einen dem punctum aequans annähernd gleichwertigen Epizykelmechanismus auf die Venusbahn verpflanzen. Vorgelegt von B. L. van der Waerden