Degeneration of unmyelinated axons in the dental root canal induced by 6-OH-dopamine

Summary The pulpal nerve fibres of feline incisors were examined ultrastructurally after i.v. administration of 6-OH-dopamine. The presence of degenerating unmyelinated fibres at this site provides conclusive morphological evidence that sympathetic fibres enter the dental pulp.     

Molecular evidence for new mutation at the hprt locus in Lesch-Nyhan patients

Hypoxanthine-guanine phosphoribosyltransferase (HPRT; EC2.4.2.8), which functions in the metabolic salvage of purines, is encoded by an X-linked gene in man. Partial HPRT deficiencies are associated with gouty arthritis, while absence of activity results in Lesch-Nyhan syndrome (L-N). L-N patients fail to reproduce and the heterozygous state appears to confer no selective advantage. Thus, Haldane's principle predicts that new mutations at the hprt locus must occur frequently in order for L-N syndrome to be maintained in the population. This constant introduction of new mutations would be expected to result in a heterogeneous collection of genetic lesions, some of which may be novel. As we report here, the mutations in the hprt gene of seven L-N patients, selected from an initial survey of 28 patients, have been characterized and all were found to be distinctly different, as predicted. The origin of one unusual mutation has been identified by analysis of DNA from four generations of family members. Further molecular analysis of the origin of new mutations at the hprt locus should aid in resolving the issue of an apparent difference in the frequency of hprt mutations in males and females.     

Crystal structure of opsin in its G-protein-interacting conformation

Opsin, the ligand-free form of the G-protein-coupled receptor rhodopsin, at low pH adopts a conformationally distinct, active G-protein-binding state known as Ops*. A synthetic peptide derived from the main binding site of the heterotrimeric G protein-the carboxy terminus of the alpha-subunit (GalphaCT)-stabilizes Ops*. Here we present the 3.2 A crystal structure of the bovine Ops*-GalphaCT peptide complex. GalphaCT binds to a site in opsin that is opened by an outward tilt of transmembrane helix (TM) 6, a pairing of TM5 and TM6, and a restructured TM7-helix 8 kink. Contacts along the inner surface of TM5 and TM6 induce an alpha-helical conformation in GalphaCT with a C-terminal reverse turn. Main-chain carbonyl groups in the reverse turn constitute the centre of a hydrogen-bonded network, which links the two receptor regions containing the conserved E(D)RY and NPxxY(x)(5,6)F motifs. On the basis of the Ops*-GalphaCT structure and known conformational changes in Galpha, we discuss signal transfer from the receptor to the G protein nucleotide-binding site.     

Head swivel on the ribosome facilitates translocation by means of intra-subunit tRNA hybrid sites

The elongation cycle of protein synthesis involves the delivery of aminoacyl-transfer RNAs to the aminoacyl-tRNA-binding site (A?site) of the ribosome, followed by peptide-bond formation and translocation of the tRNAs through the ribosome to reopen the A?site. The translocation reaction is catalysed by elongation factor G (EF-G) in a GTP-dependent manner. Despite the availability of structures of various EF-G-ribosome complexes, the precise mechanism by which tRNAs move through the ribosome still remains unclear. Here we use multiparticle cryoelectron microscopy analysis to resolve two previously unseen subpopulations within Thermus thermophilus EF-G-ribosome complexes at subnanometre resolution, one of them with a partly translocated tRNA. Comparison of these substates reveals that translocation of tRNA on the 30S subunit parallels the swivelling of the 30S head and is coupled to unratcheting of the 30S body. Because the tRNA maintains contact with the peptidyl-tRNA-binding site (P?site) on the 30S head and simultaneously establishes interaction with the exit site (E?site) on the 30S platform, a novel intra-subunit 'pe/E' hybrid state is formed. This state is stabilized by domain?IV of EF-G, which interacts with the swivelled 30S-head conformation. These findings provide direct structural and mechanistic insight into the 'missing link' in terms of tRNA intermediates involved in the universally conserved translocation process.     

Continental-scale patterns of canopy tree composition and function across Amazonia

The world's greatest terrestrial stores of biodiversity and carbon are found in the forests of northern South America, where large-scale biogeographic patterns and processes have recently begun to be described. Seven of the nine countries with territory in the Amazon basin and the Guiana shield have carried out large-scale forest inventories, but such massive data sets have been little exploited by tropical plant ecologists. Although forest inventories often lack the species-level identifications favoured by tropical plant ecologists, their consistency of measurement and vast spatial coverage make them ideally suited for numerical analyses at large scales, and a valuable resource to describe the still poorly understood spatial variation of biomass, diversity, community composition and forest functioning across the South American tropics. Here we show, by using the seven forest inventories complemented with trait and inventory data collected elsewhere, two dominant gradients in tree composition and function across the Amazon, one paralleling a major gradient in soil fertility and the other paralleling a gradient in dry season length. The data set also indicates that the dominance of Fabaceae in the Guiana shield is not necessarily the result of root adaptations to poor soils (nodulation or ectomycorrhizal associations) but perhaps also the result of their remarkably high seed mass there as a potential adaptation to low rates of disturbance.