NO-independent regulatory site on soluble guanylate cyclase

Nitric oxide (NO) is a widespread, potent, biological mediator that has many physiological and pathophysiological roles. Research in the field of NO appears to have followed a straightforward path, and the findings have been progressive: NO and cyclic GMP are involved in vasodilatation; glycerol trinitrate relaxes vascular smooth muscles by bioconversion to NO; mammalian cells synthesize NO; and last, NO mediates vasodilatation by stimulating the soluble guanylate cyclase (sGC), a heterodimeric (alpha/beta) haem protein that converts GTP to cGMP2-4. Here we report the discovery of a regulatory site on sGC. Using photoaffinity labelling, we have identified the cysteine 238 and cysteine 243 region in the alpha1-subunit of sGC as the target for a new type of sGC stimulator. Moreover, we present a pyrazolopyridine, BAY 41-2272, that potently stimulates sGC through this site by a mechanism that is independent of NO. This results in antiplatelet activity, a strong decrease in blood pressure and an increase in survival in a low-NO rat model of hypertension, and as such may offer an approach for treating cardiovascular diseases.     

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.     

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.     

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.     

Exogenous cAMP upregulates the expression of glnII and glnK-amtB genes in Sinorhizobium meliloti 1021

Sinorhizobium meliloti is a soil-borne bacterium that can lead a symbiosis life with leguminous host plants. Successful symbiont establishment requires specific recognition and progressive differentiation of both bac- teria and host cells. Once inside the plant cells of root nodules, the bacteria differentiate into non-dividing cells called bacteroids. Bacteroids obtain carbon source from the plant and, in return, they provide the plant with ammonium, and/or amino acid, as fixed nitrogen. Sign…