Reaction of vanadate ion with chlorpromazine,formation of vanadyl ion and chlorpromazine free radical

The red colored product, which was identified as a chlorpromazine (CPZ) free radical, was observed in the reaction of CPZ with the vanadate ion (+5 oxidation state). The product and the mechanism for the reaction were characterized from optical and EPR spectrometries. Optimal conditions for generation of the free radical were determined as reaction time within one minute of pH 6 and free radical stabilizing time of 30 minutes by acidifying with HCl. Under these conditions, the stoichiometry for the reaction was found to be 1:1, indicating the involvement of one electron transfer from CPZ to the vanadate ion to form the free radical and vanadyl ion (+4 oxidation state). A possible reaction scheme was proposed:

The implications of this reaction were discussed with regard to the pharmacological action of the vanadate ion and CPZ.     

CNDO/2 calculation of the relative stability of poly(γ-hydroxy-l-proline)

The CNDO/2 method using the tight-binding approximation for polymers was applied to poly(γ-hydroxy-l-prolines) (PHP). The calculations were carried out for PHPs which have the same backbone structure as those of poly(l-proline I) (Pro-I) and poly(l-proline II)(Pro-II). The results obtained show the preferred orientation of the OH group at the γ-position, which is in agreement with the experimental results. The calculations were also carried out for the B form (PHP-B). The conformational stability between the A form (PHP-A) and PHP-B was explained by using the calculated results in connection with the previous experimental and theoretical treatments. From the analysis of the total energy, the dominant stabilizing factors for the two forms are discussed.     

QUANTITATIVE CHANGES WITH AGE IN THE DNA CONTENT OF METHYLAZOXYMETHANOL-INDUCED MICROENCEPHALIC RAT BRAIN1

Abstract— DNA synthesis in methylazoxymethanol (MAM)-treated foetal brain was reduced during the first 3 days after the injection of the compound into the mother rat. The MAM-treated brain grew at almost the normal rate after this period, but the reduction in DNA persisted through maturity of the animal. This difference in DNA content between normal and microencephalic brain was restricted to the cerebral hemispheres. The major increase in DNA content of prenatal brain occurred in the cerebrum, whereas the postnatal increase took place in the cerebellum. jH-Labelled MAM was incorporated more extensively into foetal brain DNA than into RNA. The half-life of the MAM-modified nucleic acids was 4–5 days. We suggest that removal of necrotic cells from the brain may account for the rapid loss of label from nucleic acids.     

Downregulation of Rice DWARF 14 LIKE Suppress Mesocotyl Elongation via a Strigolactone Independent Pathway in the Dark

Strigolactones(SLs) are a class of plant hormones that control plant development in response to environmental conditions. In rice,mesocotyl elongation is regulated by SLs in the dark, while mesocotyls are longer in SL deficient or insensitive mutants. SLs are perceived by DWARF14(D14), which is a member of a small gene family. In this study, we examined the function of another D14 family gene in rice, D14 LIKE(D14L), focusing on mesocotyl growth. The mesocotyls of D14 L RNAi lines are longer than those of WT in the dark. This phenotype is enhanced when the D14 L RNAi lines are combined with the d14 mutation, suggesting that D14 and D14 L work independently to inhibit mesocotyl elongation. This phenotype is alleviated by the exogenous supply of GR24, a synthetic SL, suggesting that D14 L is not necessary for SL signaling. D14 L m RNA is predominantly expressed in vascular bundles and crown root primordia. Our results suggest that D14 L and D14 confer their effects via an SL independent pathway and an SL signaling pathway respectively.     

Nectin4 is an epithelial cell receptor for canine distemper virus and involved in neurovirulence

Canine distemper virus (CDV) uses signaling lymphocyte activation molecule (SLAM), expressed on immune cells, as a receptor. However, epithelial and neural cells are also affected by CDV in vivo. Wild-type CDV strains showed efficient replication with syncytia in Vero cells expressing dog nectin4, and the infection was blocked by an anti-nectin4 antibody. In dogs with distemper, CDV antigen was preferentially detected in nectin4-positive neurons and epithelial cells, suggesting that nectin4 is an epithelial cell receptor for CDV and also involved in its neurovirulence.     

Requirement of Smad3 for mast cell growth

The involvement of the TGF-beta family in cell growth of bone marrow-derived mast cells (BMMC) cultured with medium containing pokeweed mitogen-stimulated spleen cell-conditioned medium (PWM-SCM) was examined. Doubling time of BMMC from Smad3-null mice was longer than that from wild-type (WT) mice, and the differences tended to be larger with time of culture. Consistent with the results, uptake and reduction of [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; MTS] was lower in Smad3-deficient BMMC. Cell cycle analyses revealed no apparent differences between WT BMMC and Smad3-deficient BMMC, suggesting that longer doubling time in Smad3-deficient BMMC resulted from increased cell death. TGF-beta and activin A were supplied by PWM-SCM rather than by self-production by BMMC. Blocking the TGF-beta pathway by anti-TGF-beta neutralizing antibody or an inhibitor for the type I receptors for ligands including TGF-beta and activin, SB431542, inhibited MTS uptake and reduction in WT BMMC, whereas anti-activin A antibody and SB431542 tended to inhibit them in Smad3-deficient BMMC. The present results suggest that TGF-beta-induced and Smad3-mediated signaling is essential for maximal cell growth in mast cells, and that the activin pathway may be required for it when mast cell context is modulated by Smad3 depletion.     

Enhancement of insulin signaling pathway in adipocytes by oxovanadium(IV) complexes

Recently, we have found that some oxovanadium(IV) complexes are potent insulin-mimetic compounds for treating both type I and type II diabetic animals. However, the functional mechanism of oxovanadium(IV) complexes is not fully understood. In this report, we have shown that oxovanadium(IV)-picolinate complexes such as VO(pa)(2), VO(3mpa)(2), and VO(6mpa)(2) act on the insulin signaling pathway in 3T3-L1 adipocytes. Among them, VO(3mpa)(2) was found to be the highest potent activator in inducing not only the phosphotyrosine levels of both IRbeta and IRS but also the activation of downstream kinases in the insulin receptor, such as Akt and GSK3beta, which in turn translocated the insulin-dependent GLUT4 to the plasma membrane. Then, we examined whether or not oxovanadium(IV)-picolinates exhibit the hypoglycemic activity in STZ-induced diabetic mice, and found that VO(3mpa)(2) is more effective than the others in improving the hyperglycemia of the animals. Our present data indicate that both activation of insulin signaling pathway, which follows the GLUT4 translocation to the plasma membrane, and enhancement of glucose utilization by oxovanadium(IV) complexes cause the hypoglycemic effect in diabetic animals.