FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination

The precise specification of left-right asymmetry is an essential process for patterning internal organs in vertebrates. In mouse embryonic development, the symmetry-breaking process in left-right determination is initiated by a leftward extraembryonic fluid flow on the surface of the ventral node. However, it is not known whether the signal transduction mechanism of this flow is chemical or mechanical. Here we show that fibroblast growth factor (FGF) signalling triggers secretion of membrane-sheathed objects 0.3-5 microm in diameter termed 'nodal vesicular parcels' (NVPs) that carry Sonic hedgehog and retinoic acid. These NVPs are transported leftward by the fluid flow and eventually fragment close to the left wall of the ventral node. The silencing effects of the FGF-receptor inhibitor SU5402 on NVP secretion and on a downstream rise in Ca2+ were sufficiently reversed by exogenous Sonic hedgehog peptide or retinoic acid, suggesting that FGF-triggered surface accumulation of cargo morphogens may be essential for launching NVPs. Thus, we propose that NVP flow is a new mode of extracellular transport that forms a left-right gradient of morphogens.     

Genome sequencing and analysis of Aspergillus oryzae

The genome of Aspergillus oryzae, a fungus important for the production of traditional fermented foods and beverages in Japan, has been sequenced. The ability to secrete large amounts of proteins and the development of a transformation system have facilitated the use of A. oryzae in modern biotechnology. Although both A. oryzae and Aspergillus flavus belong to the section Flavi of the subgenus Circumdati of Aspergillus, A. oryzae, unlike A. flavus, does not produce aflatoxin, and its long history of use in the food industry has proved its safety. Here we show that the 37-megabase (Mb) genome of A. oryzae contains 12,074 genes and is expanded by 7-9 Mb in comparison with the genomes of Aspergillus nidulans and Aspergillus fumigatus. Comparison of the three aspergilli species revealed the presence of syntenic blocks and A. oryzae-specific blocks (lacking synteny with A. nidulans and A. fumigatus) in a mosaic manner throughout the genome of A. oryzae. The blocks of A. oryzae-specific sequence are enriched for genes involved in metabolism, particularly those for the synthesis of secondary metabolites. Specific expansion of genes for secretory hydrolytic enzymes, amino acid metabolism and amino acid/sugar uptake transporters supports the idea that A. oryzae is an ideal microorganism for fermentation.     

Recent development of high efficiency arc welding systems in Japan

Automationhasgivenapowerfulmeansto solvemanyissuesinproductionindustries,e.g.up efficiency,costreduction,manpowerproblems,en vironmentproblems,etc.Automatizationofthe weldingprocesseshavebeenremarkablypro gressedduringaboutthelasthalfcenturyandit wasbasedonthetechnologicaldevelopmentsof manyconstituentssuchas,sensorsandtheirappli cationsystemsforseamtrackingandadaptivecon trol,weldingrobot,weldingmaterial,weldingpow ersource,etc.Particularlyinthelastdecade, throughtheprogressofthecompute…     

日本住友鹿岛制铁所初轧均热炉燃烧过程模糊控制

结合日本住友鹿岛制铁所初轧均热炉燃烧过程模糊控制的实践,阐述了将模糊控制理论应用于均热炉燃烧过程控制的特点。实时控制结果表明,该系统是可行的,并取得了满意的控制效果。     

A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage

The p53 gene is frequently inactivated in human cancers. Here we have isolated a p53-inducible gene, p53R2, by using differential display to examine messenger RNAs in a cancer-derived human cell line carrying a highly regulated wild-type p53 expression system. p53R2 contains a p53-binding sequence in intron 1 and encodes a 351-amino-acid peptide with striking similarity to the ribonucleotide reductase small subunit (R2), which is important in DNA synthesis during cell division. Expression of p53R2, but not R2, was induced by ultraviolet and gamma-irradiation and adriamycin treatment in a wild-type p53-dependent manner. Induction of p53R2 in p53-deficient cells caused G2/M arrest and prevented cells from death in response to adriamycin. Inhibition of endogenous p53R2 expression in cells that have an intact p53-dependent DNA damage checkpoint reduced ribonucleotide reductase activity, DNA repair and cell survival after exposure to various genotoxins. Our results indicate that p53R2 encodes a ribonucleotide reductase that is directly involved in the p53 checkpoint for repair of damaged DNA. The discovery of p53R2 clarifies a relationship between a ribonucleotide reductase activity involved in repair of damaged DNA and tumour suppression by p53.     

CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast

In eukaryotic cells, cyclin-dependent kinases (CDKs) have an important involvement at various points in the cell cycle. At the onset of S phase, active CDK is essential for chromosomal DNA replication, although its precise role is unknown. In budding yeast (Saccharomyces cerevisiae), the replication protein Sld2 (ref. 2) is an essential CDK substrate, but its phospho-mimetic form (Sld2-11D) alone neither affects cell growth nor promotes DNA replication in the absence of CDK activity, suggesting that other essential CDK substrates promote DNA replication. Here we show that both an allele of CDC45 (JET1) and high-copy DPB11, in combination with Sld2-11D, separately confer CDK-independent DNA replication. Although Cdc45 is not an essential CDK substrate, CDK-dependent phosphorylation of Sld3, which associates with Cdc45 (ref. 5), is essential and generates a binding site for Dpb11. Both the JET1 mutation and high-copy DPB11 by-pass the requirement for Sld3 phosphorylation in DNA replication. Because phosphorylated Sld2 binds to the carboxy-terminal pair of BRCT domains in Dpb11 (ref. 4), we propose that Dpb11 connects phosphorylated Sld2 and Sld3 to facilitate interactions between replication proteins, such as Cdc45 and GINS. Our results demonstrate that CDKs regulate interactions between BRCT-domain-containing replication proteins and other phosphorylated proteins for the initiation of chromosomal DNA replication; similar regulation may take place in higher eukaryotes.     

Molecular evidence on evolutionary switching from particle-feeding to sophisticated carnivory in the calanoid copepod family Heterorhabdidae: drastic and rapid changes in functions of homologues

The oceanic calanoid copepod family Heterorhabdidae is unique in that it comprises both particle-feeding and carnivorous genera with some intermediate taxa. Both morphological and molecular (nuclear 18S and 28S rRNA) phylogenetic analyses of the family suggest that an evolutionary switch in feeding strategy, from transitions of typical particle-feeding through some intermediate modes to sophisticated carnivory, might have occurred with the development of a specially designed ‘poison’ injection system. In view of the small amount of genetic differentiation among genera in this family, the switching of feeding modes and re-colonization from deep to shallow waters might have occurred over a short geological period since the Middle to Late Miocene.     

The physical basis of how prion conformations determine strain phenotypes

A principle that has emerged from studies of protein aggregation is that proteins typically can misfold into a range of different aggregated forms. Moreover, the phenotypic and pathological consequences of protein aggregation depend critically on the specific misfolded form. A striking example of this is the prion strain phenomenon, in which prion particles composed of the same protein cause distinct heritable states. Accumulating evidence from yeast prions such as [PSI+] and mammalian prions argues that differences in the prion conformation underlie prion strain variants. Nonetheless, it remains poorly understood why changes in the conformation of misfolded proteins alter their physiological effects. Here we present and experimentally validate an analytical model describing how [PSI+] strain phenotypes arise from the dynamic interaction among the effects of prion dilution, competition for a limited pool of soluble protein, and conformation-dependent differences in prion growth and division rates. Analysis of three distinct prion conformations of yeast Sup35 (the [PSI+] protein determinant) and their in vivo phenotypes reveals that the Sup35 amyloid causing the strongest phenotype surprisingly shows the slowest growth. This slow growth, however, is more than compensated for by an increased brittleness that promotes prion division. The propensity of aggregates to undergo breakage, thereby generating new seeds, probably represents a key determinant of their physiological impact for both infectious (prion) and non-infectious amyloids.     

A neutron-star-driven X-ray flash associated with supernova SN 2006aj

Supernovae connected with long-duration gamma-ray bursts (GRBs) are hyper-energetic explosions resulting from the collapse of very massive stars ( approximately 40 M\circ, where M\circ is the mass of the Sun) stripped of their outer hydrogen and helium envelopes. A very massive progenitor, collapsing to a black hole, was thought to be a requirement for the launch of a GRB. Here we report the results of modelling the spectra and light curve of SN 2006aj (ref. 9), which demonstrate that the supernova had a much smaller explosion energy and ejected much less mass than the other GRB-supernovae, suggesting that it was produced by a star whose initial mass was only approximately 20 M\circ. A star of this mass is expected to form a neutron star rather than a black hole when its core collapses. The smaller explosion energy of SN 2006aj is matched by the weakness and softness of GRB 060218 (an X-ray flash), and the weakness of the radio flux of the supernova. Our results indicate that the supernova-GRB connection extends to a much broader range of stellar masses than previously thought, possibly involving different physical mechanisms: a 'collapsar' (ref. 8) for the more massive stars collapsing to a black hole, and magnetic activity of the nascent neutron star for the less massive stars.