Long-term changes in the population size and geographical distribution of Pennella sp. (Copepoda) on the saury,Cololabis saira,in the western North Pacific Ocean and adjacent seas

Changes in the population size and geographical distribution of the mesoparasitic copepod Pennella sp. (Siphonostomatoida: Pennellidae) on the saury, Cololabis saira, were studied for a period of six years (1981–86) in the western North Pacific Ocean and adjacent seas. The parasite was first recorded in the western North Pacific in 1981. Its population size increased rapidly in 1982–83 and declined slightly in 1984. During these years, infected fish were widely distributed in the western and central North Pacific and also found in the Sea of Okhotsk and the Sea of Japan. However, the population declined dramatically in 1985 and its distributional range was reduced. The parasite disappeared in 1986. The observed frequency distributions of parasites on the host population were the Poisson in 1981 and 1985, but those during 1982–1984 were over-dispersed and fitted the negative binomial.Parasites of the saury, Cololabis saira (Brevoort)-IV.     

Synthesis and antiviral activity of 2'-deoxy-2'-fluoro-2'-C-methyl purine nucleosides as inhibitors of hepatitis C virus RNA replication

A series of purine nucleosides containing the 2'-deoxy-2'-fluoro-2'-C-methylribofuranosyl moiety were synthesized and evaluated as potential inhibitors of the hepatitis C virus in vitro. Of the nucleosides that were synthesized, only those possessing a 2-amino group on the purine base reduced the levels of HCV RNA in a subgenomic replicon assay.     

Microelectrode array evaluation of gut pacemaker activity in wild-type and mice

Interstitial cells of Cajal in the myenteric plexus region (ICC-MyP) form a network and generate basal pacemaking electrical activity. This morphological feature leads us to believe that these cells may be essential for the coordinating actions of gastrointestinal (GI) motility. We aim to propose a new method for functional assessment of ICC electrical activity and its network. Field potentials in a 1 mm² region were simultaneously measured using an 8 × 8 microelectrode array (MEA) with a polar distance of 150 μm. The extracellular solution contained nifedipine and tetrodotoxin (TTX) to suppress activities of smooth muscle cells and neurons, respectively. We compared spatial electrical activities between ileal muscle preparations from wild-type (WT) and W/W^v mice. In spatio-temporal analyses, basal electrical activities were well synchronized with a propagation delay in WT, while those in W/W^v were small in amplitude and irregular in occurrence. The power spectrum in WT had a prominent peak corresponding to the frequency of ICC-MyP pacemaker activity, while that of W/W^v lacked it. Consequently, the ratio of the spectral power in 9.4–27.0 cpm was significantly larger in WT than in W/W^v. In conclusion, MEA measurements demonstrated that the network-forming ICC-MyP not only generates but also coordinates basal electrical activities. Disorders of GI motility based on morphological and functional impairments of ICC network with the range of several hundreds of micrometers, could be uncovered in future extensive studies.     

Essential role of STIM1 in the development of cardiomyocyte hypertrophy

Store-operated Ca²⁺ entry (SOCE) through transient receptor potential (TRP) channels is important in the development of cardiac hypertrophy. Recently, stromal interaction molecule 1 (STIM1) was identified as a key regulator of SOCE. In this study, we examined whether STIM1 is involved in the development of cardiomyocyte hypertrophy. RT-PCR showed that cultured rat cardiomyocytes constitutively expressed STIM1. Endothelin-1 (ET-1) treatment for 48 h enhanced TRPC1 expression, SOCE, and nuclear factor of activated T cells activation without upregulating STIM1. However, the knockdown of STIM1 suppressed these effects, thereby preventing a hypertrophic response. These results suggest that STIM1 plays an essential role in the development of cardiomyocyte hypertrophy.     

Genetic diversity and kinetic properties of Trypanosoma cruzi dihydroorotate dehydrogenase isoforms

Dihydroorotate dehydrogenase (DHOD) is the fourth enzyme in the de novo pyrimidine biosynthetic pathway and is essential in Trypanosoma cruzi, the parasitic protist causing Chagas' disease. T. cruzi and human DHOD have different biochemical properties, including the electron acceptor capacities and cellular localization, suggesting that T. cruzi DHOD may be a potential chemotherapeutic target against Chagas' disease. Here, we report nucleotide sequence polymorphisms of T. cruzi DHOD genes and the kinetic properties of the recombinant enzymes. T. cruzi Tulahuen strain possesses three DHODgenes: DHOD1 and DHOD2, involved in the pyrimidine biosynthetic (pyr) gene cluster on an 800 and a 1000 kb chromosomal DNA, respectively, and DHOD3, located on an 800 kb DNA. The open reading frames of all three DHOD genes are comprised of 942 bp, and encode proteins of 314 amino acids. The three DHOD genes differ by 26 nucleotides, resulting in replacement of 8 amino acid residues. In contrast, all residues critical for constituting the active site are conserved among the three proteins. Recombinant T. cruzi DHOD1 and DHOD2 expressed in E. coli possess similar enzymatic properties, including optimal pH, optimal temperature, Vmax, and Km for dihydroorotate and fumarate. In contrast, DHOD3 had a higher Vmax and Km for both substrates. Orotate competitively inhibited all three DHOD enzymes to a comparable level. These results suggest that, despite their genetic variations, kinetic properties of the three T. cruziDHODs are conserved. Our findings facilitate further exploitation of T. cruzi DHOD inhibitors, as chemotherapeutic agents against Chagas' disease.     

Effect of carbonyl compounds on red blood cells deformability

The effect of Maillard reaction on red blood cells (RBC) deformability was investigated. Exposure of RBC to carbonyl compounds (dl-glyceraldehyde, glyoxal, glycolaldehyde, 3-deoxyglucosone, and d-glucose) leading to Maillard reaction caused a marked decrease in RBC deformability even at 1 mM level. The decrease rate depended on the kind of carbonyl compounds, in which both dl-glyceraldehyde and glyoxal significantly decreased the RBC deformability (p < 0.05). In addition, the decrease rate also differed among volunteers tested, indicating that the sensitivity against carbonyl compounds varies among them. In order to elucidate the mechanism of the decrease in RBC deformability, RBC was exposed to carbonyl compounds in the presence of aminoguanidine which is the inhibitor of AGE formation in Maillard reactions. Aminoguanidine inhibited the decrease in RBC deformability by dl-glyceraldehyde and glyoxal. When Hb which has a high reactivity with carbonyl compounds was incubated with those carbonyl compounds, dl-glyceraldehyde and glyoxal showed the high reactivity with Hb compared with other carbonyl compounds. These results indicate that Maillard reaction between RBC proteins and carbonyl compounds leads to the decrease in RBC deformability. On the other hand, generated by carbonyl compounds involved in lowering the deformability only to a negligible level.