Epigenetic control of cardiomyocyte production in response to a stress during the medaka heart development

The size and morphology of organs are largely determined by a genetic program. However in some cases, an epigenetic mechanism influences the process of organ development. Particularly, epigenetic factors such as hemodynamic stress and blood pressure affect the morphogenesis of cardiac chambers and valves. Here, we report that the epigenetic influences affect the cardiomyocyte production. Taking advantage of longer developmental period of medaka fish, we could examine the later emerging tissue responses to the defect of ventricular beating, which occurred in the hozuki (hoz) mutant that harbors the mutated ventricular myosin heavy chain (vmhc) gene. The mutant showed a remarkable ventricular enlargement, and we showed that this enlargement was due to an excess production of ventricular cardiomyocytes in addition to the lack of concentric chamber growth. By experimental blockade of blood flow, we demonstrated that an elevated cardiac pressure was responsible for the aberrant cardiomyocyte production. From these data, we propose that the epigenetic tissue response to a stressed situation controls the production of cardiomyocytes to attain a fine tuning of heart formation.     

Evaluation of centrifugal methods for measuring xylem cavitation in conifers, diffuse- and ring-porous angiosperms

A centrifugal method is used to measure 'vulnerability curves' which show the loss of hydraulic conductivity in xylem by cavitation. Until recently, conductivity was measured between bouts of centrifugation using a gravity-induced head. Now, conductivity can be measured during centrifugation. This 'spin' method is faster than the 'gravity' technique, but correspondence between the two has not been evaluated. The two methods were compared on the same stem segments for two conifer, four diffuse-porous, and four ring-porous species. Only 17 of 60 conductivity measurements differed, with differences in the order of 10%. When different, the spin method gave higher conductivities at the beginning of the curve and lower at the end. Pressure at 50% loss of conductivity, and mean cavitation pressure, were the same in 14 of 20 comparisons. When different, the spin method averaged 0.32 MPa less negative. Ring-porous species showed a precipitous initial drop in conductivity by both techniques. This striking pattern was confirmed by the air-injection method and native embolism measurements. Close correspondence inspires confidence in both methods, each of which has unique advantages. The observation that ring-porous species operate at only a fraction of their potential conductivity at midday demands further study.     

Estrogenic activities of nitrophenols in diesel exhaust particles

We recently isolated 3-methyl-4-nitrophenol (4-nitro-m-cresol; PNMC) and 4-nitro-3-phenylphenol (PNMPP) from diesel exhaust particles (DEP) and identified them as vasodilators. Because these compounds are alkylphenolic derivatives that might mimic hormones, we evaluated their estrogenic activity by using recombinant yeast screens, myometrial contractility assays, and in vivo uterotrophic assays. Recombinant yeast screen assays showed that both PNMC and PNMPP possess estrogenic activity. Furthermore, ovariectomized 25-day-old immature female rats injected with PNMC and PNMPP subcutaneously for 2 days showed significant increases in uterine weight among those receiving 100 mg/kg PNMC and 0.1 and 1.0 mg/kg PNMPP. To clarify further the estrogenic activity of PNMC and PNMPP, rat uterine horns were monitored in organ bath chambers for myometrial contractility in response to oxytocin (OT). Significant differences occurred in the initial and maximum contractilities to OT at 0.25 and 25 mIU/ml in uterine horns obtained from animals treated with 100 mg/kg PNMC and in the maximum contractilities to OT at 0.025, 0.25, and 25 mIU/ml in those from rats treated with 0.1 mg/kg PNMPP. These results clearly demonstrated that PNMC and PNMPP in DEP have estrogenic activity both in vitro and in vivo and might therefore be considered as endocrine-disrupting chemicals.     

ADRP is dissociated from lipid droplets by ARF1-dependent mechanism

Adipocyte differentiation-related protein (ADRP) is a member of PAT proteins existing in lipid droplets (LDs). By yeast two-hybrid screening, we identified ADP-ribosylation factor 1 (ARF1) as a binding partner of ADRP. The interaction of ADRP and ARF1 was verified by GST pull-down and co-immunoprecipitation experiments. Interestingly, ADRP precipitated the GDP-bound ARF1 preferentially to the GTP-bound ARF1. Consistent with this, either brefeldin A (BFA), a fungal metabolite to inhibit ARF-GEF, or a dominant-negative mutant of ARF1 caused dissociation of ADRP from LD. On the other hand, overexpression of wild-type ARF1 did not promote the ADRP dissociation or new LD formation. By using deletion mutants, a central domain of ADRP, which is dispensable for LD binding, was shown to bind to ARF1. The present study showed that the GDP-bound ARF1 induces dissociation of ADRP from the LD surface, and that LD is a target of BFA action.     

Ectopic CD40 ligand expression on B cells triggers intestinal inflammation

Several studies indicate that CD4(+) T cells, macrophages, and dendritic cells initially mediate intestinal inflammation in murine models of human inflammatory bowel disease. However, the initial role of B cells in the development of intestinal inflammation remains unclear. In this study we present evidence that B cells can trigger intestinal inflammation using transgenic (Tg) mice expressing CD40 ligand (CD40L) ectopically on B cells (CD40L/B Tg). We demonstrated that CD40L/B Tg mice spontaneously developed severe transmural intestinal inflammation in both colon and ileum at 8-15 wk of age. In contrast, CD40L/B TgxCD40(-/-) double-mutant mice did not develop colitis, indicating the direct involvement of CD40-CD40L interaction in the development of intestinal inflammation. The inflammatory infiltrates consisted predominantly of massive aggregated, IgM-positive B cells. These mice were also characterized by the presence of anti-colon autoantibodies and elevated IFN-gamma production. Furthermore, although mice transferred with CD4(+) T cells alone or with both CD4(+) T and B220(+) B cells, but not B220(+) cells alone, from diseased CD40L/B Tg mice, develop colitis, mice transferred with B220(+) B cells from diseased CD40L/B Tg mice and CD4(+) T cells from wild-type mice also develop colitis, indicating that the Tg B cells should be a trigger for this colitis model, whereas T cells are involved as effectors. As it has been demonstrated that CD40L is ectopically expressed on B cells in some autoimmune diseases, the present study suggests the possible contribution of B cells in triggering intestinal inflammation in human inflammatory bowel disease.     

Nucleotide sequence of complementary DNA encoding for quaking protein of cow, horse and pig.

Complementary DNA (cDNA) for bovine quaking gene (Bqk), equine quaking gene (Eqk) and porcine quaking gene (Pqk), which are homologous to mouse quaking gene (qkI), were isolated, and their nucleotide sequences were determined. cDNA sequences of Bqk, Eqk and Pqk showed very high homology to that of qkI at nucleotide level; 94.2, 95.7 and 95.6%, respectively. Deduced amino acid sequences for Bqk, Eqk and Pqk perfectly matched to that of qkI. These findings suggest that the quaking gene family is highly conserved during mammalian evolution, and that Bqk, Eqk and Pqk are likely to have important biological functions also in cow, horse and pig.     

An efficient genetic algorithm for structural RNA pairwise alignment and its application to non-coding RNA discovery in yeast

Background  

Aligning RNA sequences with low sequence identity has been a challenging problem since such a computation essentially needs an algorithm with high complexities for taking structural conservation into account. Although many sophisticated algorithms for the purpose have been proposed to date, further improvement in efficiency is necessary to accelerate its large-scale applications including non-coding RNA (ncRNA) discovery.     

Deranged metabolism of cyclic nucleotides in liver diseases

To clarify the factor(s) responsible for changes in the plasma cyclic GMP concentration in liver diseases, we measured the plasma levels of cyclic GMP, along with cyclic AMP, in various clinical stages of chronic liver diseases and acute hepatitis. The level of cyclic GMP was found to increase significantly in the early stage of acute hepatitis, in the decompensated stage of liver cirrhosis, and in malignant diseases. In the former two states, it is postulated that decreased hepatic mass is responsible for the changes in the plasma cyclic GMP concentration. The retention rate of indocyanin green (ICGR15) was highly correlated with the plasma cyclic GMP level. The result suggests that the determination of plasma cyclic GMP is useful as an index of the reserve function of the liver in disease states.     

Leaf structural and hydraulic adjustment with respect to air humidity and canopy position in silver birch (Betula pendula)

Journal of Plant Research - Climate change scenarios predict an increase in air temperature and precipitation in northern temperate regions of Europe by the end of the century. Increasing...