Upregulation of thromboxane synthase in human colorectal carcinoma and the cancer cell proliferation by thromboxane A2

Tumor growth of colorectal cancers accompanies upregulation of cyclooxygenase-2, which catalyzes a conversion step from arachidonic acid to prostaglandin H(2) (PGH(2)). Here, we compared the expression levels of thromboxane synthase (TXS), which catalyzes the conversion of PGH(2) to thromboxane A(2) (TXA(2)), between human colorectal cancer tissue and its accompanying normal mucosa. It was found that TXS protein was consistently upregulated in the cancer tissues from different patients. TXS was also highly expressed in human colonic cancer cell lines. Depletion of TXS protein by the antisense oligonucleotide inhibited proliferation of the cancer cells. This inhibition was rescued by the direct addition of a stable analogue of TXA(2). The present results suggest that overexpression of TXS and subsequent excess production of TXA(2) in the cancer cells may be involved in the tumor growth of human colorectum.     

A geographical model of high species diversity

Several cases of high species diversity, for example in tropical rain forests, imply that speciation has been frequent or rapid. However, how speciation could proceed so frequently as to generate extraordinary diversity still remains unsolved, despite recent advancements of diverse theories of allopatric and sympatric speciation. This paper presents a theoretical model that demonstrates the process of frequent speciation by means of geographical fragmentation. We focus on allopatric speciation and explore the evolutionary effect of fragmentation and extinction of demes (subpopulations) in a widespread species or species group. After a large contagious population of a single species is fragmented into demes, extinction of some demes could result in isolation of multiple demes. Thus, several demes could become good species simultaneously through the process of allopatric speciation. We apply the random extinction method to this fragmentation process where demes become randomly extinct. The present model illustrates that frequent speciation could occur in communities where large environmental changes frequently take place.     

5′-O-Dephosphorylated 2′,5′-oligoadenylate (2-5A) with 8-methyladenosine at the 2′-terminus activates human RNase L

Human ribonuclease L (RNase L), an interferon-induced endoribonuclease, becomes enzymatically active after binding to 2-5A. The 5′-phosphoryl group of 2-5A is reportedly necessary for the conformational change leading to RNase L activation. However, we found that 5′-O-dephosphorylated 2-5A tetramer analogs with 8-methyladenosine at the 2′-terminus were more effective as an activator of RNase L than the parent 2-5A tetramer. Introduction of 8-methyladenosine is thought to induce a dramatic shift of 2-5A in the binding site of RNase L.     

Biochemical screening of stable dinucleosomes using DNA fragments from a dinucleosome DNA library

The dinucleosome is an informative unit for analysis of the higher-order chromatin structure. DNA fragments forming stable dinucleosomes were screened from a dinucleosome DNA library after the reconstitution of nucleosomes in vitro and digestion with micrococcal nuclease. Reconstituted dinucleosomes showed a diversity of sensitivity to micrococcal nuclease, suggesting that the biochemical stability of a dinucleosome depends, in part, on the DNA fragments. The DNA fragments after the screening were classified into three groups represented by clones bf10, af14 and af32 according to the sensitivity to micrococcal nuclease. Mapping of the nucleosome boundaries by Southern blotting of the DNA after restriction digestion and by primer extension analysis showed that each nucleosome position of clone af32 was fixed. Analysis of reconstituted dinucleosomes using mutant DNA fragments of clone af32 revealed a unique property characteristic of a key nucleosome, given that the replacement of a DNA fragment corresponding to the right nucleosome position resulted in marked sensitivity to micrococcal nuclease, whereas the replacement of the other nucleosome fragment had almost no effect on sensitivity as compared to the original af32 construct. The mutant construct in which the right nucleosome was removed showed multiple nucleosome phases, suggesting that the right nucleosome stabilized first each mononucleosome and then the dinucleosome. An oligonucleotide bending assay revealed that the DNA fragment in the right nucleosome included curved DNA, suggesting that the positioning activity of the nucleosome was attributed to its DNA structure. These results suggest that information for forming stable dinucleosome is embedded in the genomic DNA and that a further characterization of the key nucleosome is useful for understanding the building up of the chromatin structure.     

Rice plant development: from zygote to spikelet

Rice is becoming a model plant in monocotyledons and a model cereal crop. For better understanding of the rice plant, it is essential to elucidate the developmental programs of the life cycle. To date, several attempts have been made in rice to categorize the developmental processes of some organs into substages. These studies are based exclusively on the morphological and anatomical viewpoints. Recent advancement in genetics and molecular biology has given us new aspects of developmental processes. In this review, we first describe the phasic development of the rice plant, and then describe in detail the developmental courses of major organs, leaf, root and spikelet, and specific organs/tissues. Also, for the facility of future studies, we propose a staging system for each organ.     

Update of mouse microsatellite database of Japan (MMDBJ).

We updated a database of microsatellite marker polymorphisms found in inbred strains of the mouse, most of which were derived from the wild stocks of four Mus musculus subspecies, M. m. domesticus, M. m. musculus, M. m.castaneus and M. m. molossinus. The major aim of constructing this database was to establish the genetic status of these inbred strains as resources for linkage analysis and positional cloning. The inbred strains incorporated in our database are A/J, C57BL/6J, CBA/J, DBA/2J, SM/J, SWR/J, 129Sv/J, MSM/Ms, JF1/Ms, CAST/Ei, NC/Nga, BLG2/Ms, NJL/Ms, PGN2/Ms, SK/CamEi and SWN/Ms, which have not or have only been poorly incorporated in the Whitehead Institute/MIT (WI/MIT) microsatellite database. The number of polymorphic microsatellite loci incorporated in our database is over 1,000 in all strains, and the URL site for our database is located at http:// www.shigen.nig.ac.jp /mouse/mmdbj/mouse.html.     

An efficient synthesis of methyl tetra-o-hexyl gentiooctaoside, an octaosyl analogue of ANP receptor antagonist HS-142-1

Methyl

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, a 3-O hexyl analogue of the octaosyl component of fungal lipooligosaccharide HS-142-1, was stereo- and regioselectively synthesized as a potent antagonist for the tetrameric atrial natriuretic peptide (ANP) receptors.     

Virulence-defective strains of Salmonella enterica serovar Typhi as candidates for education at level 2 facilities

The use of biosafety level 3 pathogens is an essential element of education and training at medical schools. We previously reported on invasion-defective strains of Salmonella enterica serovar Typhi, GTC 3P408 (DeltainvA, DeltasipB) and GTC 3P409 (DeltainvA, DeltasipB, and DeltaviaB), as candidates for use in educational programs. Vi negative strains of S. enterica serovar Typhi became extremely sensitive to complement attack but showed increased invasiveness. Therefore, this study was conducted to construct two virulencedefective strains, GTC 3P460 (DeltainvA, DeltasipB, and DeltarpoS) and GTC 3P461 (DeltainvA, DeltasipB, DeltaviaB, and DeltarpoS), of S. enterica serovar Typhi by deleting rpoS from the GTC 3P409 and GTC 3P408 strains. Stress tests demonstrated that GTC 3P460 and GTC 3P461 are sensitive to conditions of starvation, acid stress and oxidative stress. These results suggest that these virulence-defective strains have difficulty surviving in the gastric environment and in macrophages, characteristics that make them ideal candidates for education at level 2 facilities. Colony morphology and conventional biochemical features of these strains are identical to the parent strain S. enterica serovar Typhi GIFU 10007.