Identification of arylsulfonamides as Aquaporin 4 inhibitors

Carbonic anhydrase inhibitors AZA, EZA, and 4-acetamidobenzsulfonamide were found to inhibit human AQP4-M23 mediated water transport by 80%, 68%, and 23%, respectively, at 20 microM in an in vitro functional assay. AZA was found to have an IC50 against AQP4 of 0.9 microM. Phloretin was inactive under the same conditions.     

Serum levels of sRAGE, the soluble form of receptor for advanced glycation end products, are associated with inflammatory markers in patients with type 2 diabetes

Advanced glycation end products (AGEs) and their receptor (RAGE) play an important role in accelerated atherosclerosis in diabetes. We have recently found that the soluble form of RAGE (sRAGE) levels are significantly higher in type 2 diabetic patients than in nondiabetic subjects and positively associated with the presence of coronary artery disease in diabetes. In this study, we examined whether serum levels of sRAGE correlated with inflammatory biomarkers in patients with type 2 diabetes. Eighty-six Japanese type 2 diabetic patients (36 men and 50 women, mean age 68.4+/-9.6 years) underwent a complete history and physical examination, determination of blood chemistries, sRAGE, monocyte chemotactic protein-1 (MCP-1), adiponectin, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). Univariate regression analysis showed that serum levels of sRAGE positively correlated with alanine aminotransferase (ALT) (r=0.437, P=0.0001), MCP-1 (r=0.359, P=0.001), TNF-alpha (r=0.291, P=0.006), and hyperlipidemia medication (r=0.218, P=0.044). After multiple regression analyses, ALT (P<0.0001), MCP-1 (P=0.007), and TNF-alpha (P=0.023) remained significant. The present study demonstrates for the first time that serum levels of sRAGE are positively associated with MCP-1 and TNF-alpha levels in type 2 diabetic patients. These observations suggest the possibility that sRAGE level may become a novel biomarker of vascular inflammation in type 2 diabetic patients.     

Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium

Infection with Helicobacter pylori (H. pylori) is a risk factor for the development of gastric cancer. Here we show that infection of gastric epithelial cells with 'cag' pathogenicity island (cagPAI)-positive H. pylori induced aberrant expression of activation-induced cytidine deaminase (AID), a member of the cytidine-deaminase family that acts as a DNA- and RNA-editing enzyme, via the IkappaB kinase-dependent nuclear factor-kappaB activation pathway. H. pylori-mediated upregulation of AID resulted in the accumulation of nucleotide alterations in the TP53 tumor suppressor gene in gastric cells in vitro. Our findings provide evidence that aberrant AID expression caused by H. pylori infection might be a mechanism of mutation accumulation in the gastric mucosa during H. pylori-associated gastric carcinogenesis.     

Polyporus phyllostachydis sp. nov. with notes on other rhizophilic species of Polyporus (Basidiomycota,Polyporaceae)

Polyporus phyllostachydis is described and illustrated as a new species. This species is characterized by its occurrence on bamboo roots, the small and centrally stipitate basidiocarps, the white pileus, usually becoming darker from the center at maturity, and the cylindrical stipe with a distinct crust. Morphological characters of the present species were compared with those of P. cryptopus and P. rhizophilus, other rhizophilic species of the genus. Polyporus cryptopus and P. rhizophilus are morphologically distinct by contextual texture, basidiospores, and hyphae, and possibly represent two distinct species. Contribution no. 205, Laboratory of Plant Parasitic Mycology, Graduate School of Life and Environmental Sciences, University of Tsukuba, Japan     

The positive effect of the decreased NADPH-preferring activity of xylose reductase from Pichia stipitis on ethanol production using xylose-fermenting recombinant Saccharomyces cerevisiae

We focused on the effects of a mutation of xylose reductase from Pichia stipitis (PsXR) on xylose-to-ethanol fermentation using recombinant Saccharomyces cerevisiae transformed with PsXR and PsXDH (xylitol dehydrogenase from P. stipitis) genes. Based on inherent NADH-preferring XR and several site-directed mutagenetic studies using other aldo-keto reductase enzymes, we designed several single PsXR mutants. K270R showing decreased NADPH-preferring activity without a change in NADH-preferring activity was found to be a potent mutant. Strain Y-K270R transformed with K270R PsXR and wild-type PsXDH showed a 31% decrease in unfavorable xylitol excretion with 5.1% increased ethanol production as compared to the control in the fermentation of 15 g l(-1) xylose and 5 g l(-1) glucose.     

Molecular cloning and functional expression of soybean allene oxide synthases

A plant allene oxide synthase (AOS) reacting with 13S-hydroperoxy-9Z,11E,15Z-octadecatrienoic acid (13-HPOT), a lipoxygenase product of alpha-linolenic acid, provides an allene oxide which functions as an intermediate for jasmonic acid (JA) synthesis, making AOS a key enzyme regulating the JA level in plants. Although AOSs in various plants have been investigated, there is only limited information about AOSs in soybean (Glycine max). In this study, we cloned and characterized two soybean AOSs, GmAOS1 and GmAOS2, sharing 95% homology in the predicted amino acid sequences. GmAOS1 and GmAOS2 were composed of 564 and 559 amino acids respectively, with predicted N-terminal chloroplast-targeting signal peptides. Both AOSs expressed in Escherichia coli were selective for 13S-hydroperoxides of alpha-linolenic and linoleic acids, suggesting the potential of GmAOS1 and GmAOS2 to contribute to JA synthesis. GmAOS1 and GmAOS2 were expressed in leaves, stems, and roots, suggesting broad distribution in a soybean plant.     

Sterol biosynthesis by a prokaryote: first in vitro identification of the genes encoding squalene epoxidase and lanosterol synthase from Methylococcus capsulatus

Sterol biosynthesis by prokaryotic organisms is very rare. Squalene epoxidase and lanosterol synthase are prerequisite to cyclic sterol biosynthesis. These two enzymes, from the methanotrophic bacterium Methylococcus capsulatus, were functionally expressed in Escherichia coli. Structural analyses of the enzymatic products indicated that the reactions proceeded in a complete regio- and stereospecific fashion to afford (3S)-2,3-oxidosqualene from squalene and lanosterol from (3S)-2,3-oxidosqualene, in full accordance with those of eukaryotes. However, our result obtained with the putative lanosterol synthase was inconsistent with a previous report that the prokaryote accepts both (3R)- and (3S)-2,3-oxidosqualenes to afford 3-epi-lanosterol and lanosterol, respectively. This is the first report demonstrating the existence of the genes encoding squalene epoxidase and lanosterol synthase in prokaryotes by establishing the enzyme activities. The evolutionary aspect of prokaryotic squalene epoxidase and lanosterol synthase is discussed.     

Research and control of parasitic diseases in Japan: current position and future perspectives

Between 1950 and 1980, Japan eliminated several major parasitic diseases. In 1998, the Japanese Hashimoto Initiative was the first global programme to target parasitic diseases. Thereafter, Japan expanded its international cooperation to cover infectious diseases through integrated development programmes to improve health, to alleviate poverty and to help to achieve the Millennium Development Goals of the United Nations. Parasite control remains a major component of all subsequent operations. Opportunities to build upon past successes in order to improve the situation in the developing world - in addition to tackling emerging national threats - are promising. Substantial challenges remain and Japan has introduced major national reforms to try to overcome them.     

Past Japanese successes show the way to accomplish future goals

Many parasitic diseases have been eradicated in industrialized countries and well-proven tools and techniques exist to control them. However, the same diseases still cause incalculable ill health and suffering in the developing world. The difficulty remains how best to apply existing solutions where they are most needed. Within a period of 25 years following World War II, Japan eliminated many parasitic diseases and raised national health and living standards to world-leading levels. Gradually, the predominantly community-driven and intersectoral collaborative partnership systems (i.e. private sector, public sector, general public, etc.) and practices that worked in Japan are being extended to Asia and now Africa. These are backed by the provision of substantial human and financial resources from a nation whose population retains the reputation as being the healthiest and longest living in the world.     

Biophysical stability and enzymatic recognition of oxanine in DNA

Oxanine (Oxa), which is one of the major products generated from guanine by nitrosative oxidation and is as long-lived as Gua in DNA, has been thought to be one of the major causes for NO-induced DNA damage. In the present study, using several synthetic Oxa-containing oligodeoxynucleotides, biophysical stability and enzymatic recognition of Oxa was investigated in DNA strands. It was found that Oxa did not mediate marked distortion in the whole DNA structure although Oxa pairing with 4 normal bases decreased thermal stability of the DNA duplexes compared to Gua:Cyt base pair. Regarding the responses of the DNA-relevant enzymes to Oxa, it was determined that Oxa was recognized as Gua except that DNA polymerases incorporated Thy as well as Cyt opposite Oxa. These results imply that Oxa tends to behave as a kind of naturally occurring base, Gua and therefore, would be involved in the genotoxic and cytotoxic threats of NO in cellular system.