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.     

四川龙门山中段变形和变质历史(英文)

在龙门山的中段,四川盆地西缘的逆冲断层起源于紧靠汶川-茂汶断裂西侧的变质“根带”。汶川-茂汶断裂代表一条20～25km宽的剪切带的晚期脆性变形阶段。该剪切带活动于大约200Ma前的印支期。在汶川-茂汶剪切带北西侧的松潘-甘孜褶皱带中,印支期的NE-SW向挤压形成D_1逆冲断层,并被NW向F_2直立褶皱所叠加。当松潘-甘孜褶皱带受到D_1-D_2期缩短时,相邻的四川盆地并没有发生变形。两个地区的差异应变被发育于D_3的汶川-茂汶左行剪切带所容纳。松潘-甘孜褶皱带中持续的NE-SW向缩短导致了龙门山地区的SE向挤压。这种SE向挤压引起沿汶川-茂汶剪切带发生局部地壳加厚和巴罗型(Barrovian-type)变质作用。汶川-茂汶剪切带的运动学特点由D_3的左行剪切逐渐转变为D_4的SE向逆冲。这种逆冲作用引起了变质地区的初步隆起,以及龙门山地区第一期推覆体的就位。在印支期变形的后期(D_5),岩石发生褶皱并被花岗岩体侵入。现在的汶川-茂汶断裂位置是在更晚的变形阶段确立的。这个阶段的变形可能导致了彭灌基底杂岩沿着映秀-北川断裂发生隆起。在这一事件中,汶川-茂汶断裂是作为一条具有显著左行走滑分量的脆性正断层活动的。这一事件可能对应于龙门山地区的第二期推覆体运动,并且可能发生于侏罗纪—第三纪之间,或者是在喜马拉雅期。     

Inactivation of the p53 pathway in retinoblastoma

Most human tumours have genetic mutations in their Rb and p53 pathways, but retinoblastoma is thought to be an exception. Studies suggest that retinoblastomas, which initiate with mutations in the gene retinoblastoma 1 (RB1), bypass the p53 pathway because they arise from intrinsically death-resistant cells during retinal development. In contrast to this prevailing theory, here we show that the tumour surveillance pathway mediated by Arf, MDM2, MDMX and p53 is activated after loss of RB1 during retinogenesis. RB1-deficient retinoblasts undergo p53-mediated apoptosis and exit the cell cycle. Subsequently, amplification of the MDMX gene and increased expression of MDMX protein are strongly selected for during tumour progression as a mechanism to suppress the p53 response in RB1-deficient retinal cells. Our data provide evidence that the p53 pathway is inactivated in retinoblastoma and that this cancer does not originate from intrinsically death-resistant cells as previously thought. In addition, they support the idea that MDMX is a specific chemotherapeutic target for treating retinoblastoma.     

Phosphorylated derivatives of the cytokinins,zeatin and its 9-β-d-ribofuranoside,naturally occurring adenine and adenosine derivatives with plant cell-division promoting activity

Zusammenfassung Zeatin-ribosid-5-phosphat wurde einerseits durch Umsetzung von 6-Chlorpurin-ribotid mit trans-4-Amino-2-methylbuten-(2)-ol-(1) und andererseits durch Behandlung von Isopropyliden-zeatin-ribosid mit Pyrophosphorylchlorid hergestellt. Die Phosphorylierung des Isopropylidenderivats in Pyridin ergab ein Allylpyridiniumderivat, dessen Struktur spektroskopisch und durch Abbau bewiesen wurde.     

Genetic dissection of autoimmune type I diabetes in the BB rat.

The BB rat is among the best models of insulin-dependent diabetes mellitus--with onset and pathogenesis closely resembling the human disease. One unusual feature is a severe T-cell lymphopenia, which appears to be inherited as a recessive trait controlled by a single gene, Lyp. Based on genetic analysis of several crosses, we show that development of diabetes involves at least three genes: Lyp, which is tightly linked to the neuropeptide Y (Npy) gene on chromosome 4, a gene linked to the major histocompatibility complex (MHC) on chromosome 20, and a third unmapped gene for which the Fischer rat strain carries an allele conferring resistance.     

Individual-specific 'fingerprints' of human DNA

Simple tandem-repetitive regions of DNA (or 'minisatellites') which are dispersed in the human genome frequently show substantial length polymorphism arising from unequal exchanges which alter the number of short tandem repeats in a minisatellite. We have shown previously that the repeat elements in a subset of human minisatellites share a common 10-15-base-pair (bp) 'core' sequence which might act as a recombination signal in the generation of these hypervariable regions. A hybridization probe consisting of the core repeated in tandem can detect many highly polymorphic minisatellites simultaneously to provide a set of genetic markers of general use in human linkage analysis. We now show that other variant (core)n probes can detect additional sets of hypervariable minisatellites to produce somatically stable DNA 'fingerprints' which are completely specific to an individual (or to his or her identical twin) and can be applied directly to problems of human identification, including parenthood testing.