Following the signal sequence from ribosomal tunnel exit to signal recognition particle

Membrane and secretory proteins can be co-translationally inserted into or translocated across the membrane. This process is dependent on signal sequence recognition on the ribosome by the signal recognition particle (SRP), which results in targeting of the ribosome-nascent-chain complex to the protein-conducting channel at the membrane. Here we present an ensemble of structures at subnanometre resolution, revealing the signal sequence both at the ribosomal tunnel exit and in the bacterial and eukaryotic ribosome-SRP complexes. Molecular details of signal sequence interaction in both prokaryotic and eukaryotic complexes were obtained by fitting high-resolution molecular models. The signal sequence is presented at the ribosomal tunnel exit in an exposed position ready for accommodation in the hydrophobic groove of the rearranged SRP54 M domain. Upon ribosome binding, the SRP54 NG domain also undergoes a conformational rearrangement, priming it for the subsequent docking reaction with the NG domain of the SRP receptor. These findings provide the structural basis for improving our understanding of the early steps of co-translational protein sorting.     

Hydrological response to a seafloor spreading episode on the Juan de Fuca ridge

Seafloor hydrothermal systems are known to respond to seismic and magmatic activity along mid-ocean ridges, often resulting in locally positive changes in hydrothermal discharge rate, temperature and microbial activity, and shifts in composition occurring at the time of earthquake swarms and axial crustal dike injections. Corresponding regional effects have also been observed. Here we present observations of a hydrological response to seafloor spreading activity, which resulted in a negative formation-fluid pressure transient during and after an earthquake swarm in the sediment-sealed igneous crust of the Middle Valley rift of the northernmost Juan de Fuca ridge. The observations were made with a borehole seal and hydrologic observatory originally established in 1991 to study the steady-state pressure and temperature conditions in this hydrothermally active area. The magnitude of the co-seismic response is consistent with the elastic strain that would be expected from the associated earthquakes, but the prolonged negative pressure transient after the swarm is surprising and suggests net co-seismic dilatation of the upper, permeable igneous crust. The rift valley was visited four weeks after the onset of the seismic activity, but no signature of increased hydrothermal activity was detected in the water column. It appears that water, not magma, filled the void left by this spreading episode.     

Sequential proteome alterations during genesis and progression of colon cancer

Changes in the proteome of colon mucosal cells accompany the transition from normal mucosa via adenoma and invasive cancer to metastatic disease. Samples from 15 patients with sporadic sigmoid cancers were analyzed. Proteins were separated by two-dimensional gel electrophoresis. Relative differences in expression levels between normal tissue, adenoma, carcinoma and metastasis were evaluated in both intra- and inter-patient comparisons. Up- and down-regulated proteins (<twofold) during development to cancer or metastasis were excised and submitted to peptide mass fingerprinting and MS/MS sequence analysis, facilitated by the use of a compact disc workstation. In total, 112 protein spots were found to be differentially regulated, of which 72 were determined as to protein identity, 46 being up-regulated toward the progression of cancer, and 26 down-regulated. Several of the identifications correlate with proteins of the cell cycle, cytoskeleton or metabolic pathways. The pattern changes now identified have the potential for design of marker panels for assistance in diagnostics and therapeutic strategies in colorectal cancer.Received 2 February 2004; received after revision 16 March 2004; accepted 18 March 2004     

Multi-colour organic light-emitting displays by solution processing

Organic light-emitting diodes (OLEDs) show promise for applications as high-quality self-emissive displays for portable devices such as cellular phones and personal organizers. Although monochrome operation is sufficient for some applications, the extension to multi-colour devices--such as RGB (red, green, blue) matrix displays--could greatly enhance their technological impact. Multi-colour OLEDs have been successfully fabricated by vacuum deposition of small electroluminescent molecules, but solution processing of larger molecules (electroluminescent polymers) would result in a cheaper and simpler manufacturing process. However, it has proved difficult to combine the solution processing approach with the high-resolution patterning techniques required to produce a pixelated display. Recent attempts have focused on the modification of standard printing techniques, such as screen printing and ink jetting, but those still have technical drawbacks. Here we report a class of electroluminescent polymers that can be patterned in a way similar to standard photoresist materials--soluble polymers with oxetane sidegroups that can be crosslinked photochemically to produce insoluble polymer networks in desired areas. The resolution of the process is sufficient to fabricate pixelated matrix displays. Consecutive deposition of polymers that are luminescent in each of the three RGB colours yielded a device with efficiencies comparable to state-of-the-art OLEDs and even slightly reduced onset voltages.     

Efficient mixing of the solar nebula from uniform Mo isotopic composition of meteorites

The abundances of elements and their isotopes in our Galaxy show wide variations, reflecting different nucleosynthetic processes in stars and the effects of Galactic evolution. These variations contrast with the uniformity of stable isotope abundances for many elements in the Solar System, which implies that processes efficiently homogenized dust and gas from different stellar sources within the young solar nebula. However, isotopic heterogeneity has been recognized on the subcentimetre scale in primitive meteorites, indicating that these preserve a compositional memory of their stellar sources. Small differences in the abundance of stable molybdenum isotopes in bulk rocks of some primitive and differentiated meteorites, relative to terrestrial Mo, suggest large-scale Mo isotopic heterogeneity between some inner Solar System bodies, which implies physical conditions that did not permit efficient mixing of gas and dust. Here we report Mo isotopic data for bulk samples of primitive and differentiated meteorites that show no resolvable deviations from terrestrial Mo. This suggests efficient mixing of gas and dust in the solar nebula at least to 3 au from the Sun, possibly induced by magnetohydrodynamic instabilities. These mixing processes must have occurred before isotopic fractionation of gas-phase elements and volatility-controlled chemical fractionations were established.     

Dominance of one T-cell receptor in the H-2Kb/TNP response

T-cell receptors (TCRs) recognize foreign antigens in the context of major histocompatibility complex (MHC)-encoded cell surface proteins. These receptors are heterogeneous, dimeric glycoproteins composed of disulphide linked alpha- and beta-chains. We analysed the diversity of TCRs in a collection of H-2Kb-restricted, 2,4,6-trinitrophenyl (TNP)-specific (H-2Kb/TNP) cytotoxic T-cell (Tc) clones from C57BL/6 mice. Investigation of the beta-chain messenger RNAs revealed that nearly half of these independent clones expressed an identical beta-chain gene. We show here that almost all the Tc clones expressing the predominant beta-chain gene also express an identical alpha-chain gene. These results show that a strong selective pressure acted on the Tc population, resulting in a skewing of the TCR repertoire for H-2Kb/TNP and in the dominant expression of one TCR with this specificity. Possible explanations for this skewing include antigen-driven clonal expansion and network interactions.     

Mutations in different components of FGF signaling in LADD syndrome

Lacrimo-auriculo-dento-digital (LADD) syndrome is characterized by lacrimal duct aplasia, malformed ears and deafness, small teeth and digital anomalies. We identified heterozygous mutations in the tyrosine kinase domains of the genes encoding fibroblast growth factor receptors 2 and 3 (FGFR2, FGFR3) in LADD families, and in one further LADD family, we detected a mutation in the gene encoding fibroblast growth factor 10 (FGF10), a known FGFR ligand. These findings increase the spectrum of anomalies associated with abnormal FGF signaling.