Computational methods in molecular diversity and combinatorial chemistry

(+)-MK-801 is known to be a specific non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors. However, besides having an anticonvulsant effect, this compound possesses a central sympathomimetic effect and an anxiolytic-like action, raising the possibility that (+)-MK-801 might affect monoamine uptake systems. To elucidate this possibility, we investigated the effects of (+)-MK-801 on monoamine transporters expressed in HEK cells. (+)-MK-801 significantly inhibited the uptake of all three monoamine transporters in a dose-dependent manner and the inhibitions were competitive with respect to monoamines. The Ki values of (+)-MK-801 on the norepinephrine, dopamine and serotonin transporters were 3.2 microM, 40 microM and 43 microM, respectively. In addition, (-)-MK-801, a less potent antagonist of NMDA receptors, also inhibited monoamine transporters with a similar potency as that of (+)-MK-801. These results clearly indicate that MK-801, a non-competitive antagonist of NMDA receptors, competitively inhibits monoamine transporters without stereoselectivity.     

StAR protein is expressed in both medulla and cortex of the bovine and rat adrenal gland

We have employed polyclonal antibodies to a peptide sequence of bovine steroidogenic acute regulatory (StAR) protein and human placental 3beta-hydroxysteroid dehydrogenase (3beta-HSD) to determine the localisation and distribution of these proteins in rat and bovine adrenal glands. Immunohistochemical staining demonstrated the presence of StAR protein in the zona glomerulosa (ZG), zona fasciculata (ZF), zona reticularis (ZR) and in the medulla of both species. For 3beta-HSD, immunostaining was observed in the ZG, ZF and ZR of the rat adrenal and was absent in the medulla. Immunoblotting experiments showed intense bands for StAR protein (30 kDa, 37 kDa) in the mitochondria of bovine ZG, ZF and medulla and a less intense band (30 kDa) in the microsomes. In rat ZG and ZF/R mitochondria only the 30 kDa protein was present. For 3beta-HSD, an intense band (42 kDa) was found in microsomes and mitochondria of rat and bovine ZG and ZFR. A very faint signal for 3beta-HSD was seen in adrenal medulla. In conclusion, StAR (or a closely related) protein is present throughout the adrenal gland in rat and bovine species in contrast to 3beta-HSD which is confined to the steroidogenic zones. The possible function of StAR protein in the adrenal medulla merits investigation.     

Modulation of cytochrome P-450-dependent monooxygenases, glutathione and glutathione S-transferase in rat liver by geniposide from Gardenia jasminoides

Geniposide is an iridoid glycoside extracted from the fruits of Gardenia jasminoides, which are used as a food colorant and as a traditional Chinese medicine for treatment of hepatic and inflammatory diseases. The effects of geniposide and G. jasminoides fruit crude extract on liver cytochrome P-450 (P-450)-dependent monooxygenases, glutathione and glutathione S-transferase were investigated using rats treated orally with the iridoid glycoside (0.1 g/kg body weight/day) or the fruit crude extract (2 g/kg/day) for 4 days. The treatments decreased serum urea nitrogen level but increased liver to body weight ratio, total hepatic glutathione content and hepatic cytosolic glutathione S-transferase activity. Treatments with geniposide and G. jasminoides decreased P-450 content, benzo[a]pyrene hydroxylation, 7-ethoxycoumarin O-deethylation, and erythromycin N-demethylation activities in liver microsomes without affecting aniline hydroxylation activity. The natural products had no effect on glutathione content and monooxygenase activities in kidney microsomes. Immunoblotting analyses of liver microsomal proteins using mouse monoclonal antibody 2-13-1 to rat P4503A1/2 revealed that geniposide and G. jasminoides crude extract decreased the intensity of a P4503A-immunorelated protein. Protein blots probed with mouse monoclonal antibody 1-12-3 to rat P4501A1 and rabbit polyclonal antibody against human P4502E1 showed that both treatments had little or no effect on P4501A and 2E proteins. The present findings demonstrate that geniposide from G. jasminoides has the ability to inhibit a P4503A monooxygenase and increase glutathione content in rat liver.     

Genetic Deletion of HLJ1 Does Not Affect Blood Coagulation in Mice

HLJ1 (also called DNAJB4) is a member of the DNAJ/Hsp40 family and plays an important role in regulating protein folding and activity. However, there is little information about the role of HLJ1 in the regulation of physiological function. In this study, we investigated the role of HLJ1 in blood coagulation using wild-type C57BL/6 mice and HLJ1-null (HLJ1^-/-) mice. Western blot analysis and immunohistochemistry were used to assess the expression and distribution of HLJ1 protein, respectively. The tail bleeding assay was applied to assess the bleeding time and blood loss. A coagulation test was used for measuring the activity of extrinsic, intrinsic and common coagulation pathways. Thromboelastography was used to measure the coagulation parameters in the progression of blood clot formation. The results showed that HLJ1 was detectable in plasma and bone marrow. The distribution of HLJ1 was co-localized with CD41, the marker of platelets and megakaryocytes. However, genetic deletion of HLJ1 did not alter blood loss and the activity of extrinsic and intrinsic coagulation pathways, as well as blood clot formation, compared to wild-type mice. Collectively, these findings suggest that, although HLJ1 appears in megakaryocytes and platelets, it may not play a role in the function of blood coagulation under normal physiological conditions.     

Crystallization of Li2O · Al2O3· 6SiO2 Glasses Containing Niobium Pentoxide as Nucleating Dopant

Niobium pentoxide (T form, orthorhombic system) was utilized to promote devitrification in Li₂O · Al₂O₃· 6SiO₂ glasses. Two or more mole percentage of this nucleating dopant enhanced crystallization in these glasses. Glasses containing 4.0 and 8.0 mol% T-Nb₂O₅ exhibited a high tendency to form dispersed TT-Nb₂O₅ (monoclinic system) precipitates during the glass quenching process. The crystallization process in glasses containing 2.0 or 4.0 mol% T-Nb₂O₅ occurred as microphase separation, followed by the formation of dispersed TT-Nb₂O₅ crystalline precipitates (760°C), followed by β-quartz solid-solution ( ss ) formation (850° to 900°C) heterogeneously nucleated from the precipitates. β-quartz( ss ) transformed to β-spodumene( ss ), along with a polymorphic transition from the TT-Nb₂O₅ to M-Nb₂O₅ (tetragonal system) crystalline phase.     

The effects of catalyst surface heterogeneity on the fischer-tropsch synthesis

We find that the surface energetic heterogeneity of Fischer-Tropsch catalysts is either not important kinetically or may be masked by the effect of increasing molecular size, so that the classical Anderson-Schulz-Flory distribution is routinely observed in product distributions. The anomalous yields of C₁ and C₂ observed in many cases may also be due to surface heterogeneity but can in practice be readily, and more conveniently, accounted for by assigning individual rate constants to their formation. The “break” sometimes observed in ASF distributions cannot be explained by surface heterogeneity and is best explained by the presence of two distinct modes of product formation.     

Densification,microstructure and microwave dielectric properties of ultra-low fire BaTe4O9–TiTe3O8 ceramic composites

In this study, BaTe₄O₉–TiTe₃O₈ ceramic composites with various amounts of TiTe₃O₈ were prepared, and the densification, microstructural evolution, and dielectric properties of the ultra-low fire ceramic composites were characterized. With the addition of TiTe₃O₈, the ceramic composites were densified at 575 °C with the maximum densities ranging from 93% to 96% of theoretical density. Except the BaTe₄O₉ and TiTe₃O₈ phases, no other second phase was observed in the XRD results. The change in the microstructures caused by the increase of TiTe₃O₈ content appeared to be insignificant. Wide grain size distributions with angular grains in the range of 1–4 μm were observed for all cases. The best dielectric properties – ?_r value of 25, Q × f value of 19,340 GHz, and τ_f value of ?2.7 ppm/°C – were obtained for BaTe₄O₉–40 wt% TiTe₃O₈ ceramic composite sintered at 575 °C, qualifying the ultra-low fire composites for use in the application of ceramic resonators.     

An amphoteric water‐soluble copolymer. II. Effect of its molecular weight on the dispersion of barium titanate in water

An amphoteric water‐soluble copolymer, that is, polyacrylamide/(α‐N,N‐dimethyl‐N‐acryloyloxyethyl)ammonium ethanate (PAAM/DAAE) was synthesized and it showed the ability to disperse BaTiO₃ (BT) particles in aqueous solutions. In this work, the effect of molecular weight of this polymer on the dispersing properties was further examined. The results indicate that the effectiveness of three polymer samples with different molecular weights in the dispersion of BT particles is P2 (M_w = 1.1 × 10⁵) > P1 (M_w = 1.2 × 10⁴) > P3 (M_w = 3.0 × 10⁵). Apparently, P2 is most effective in dispersing the particles, reducing the viscosity of the suspensions, and obtaining highest green and sintered densities. This is attributed to the highest adsorption of this polymer onto BT powder, and causes strongest electrostatic and steric repulsions. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 886–891, 2006     

Bending-beam measurement of solvent diffusions in polyimides: Theoretical and experimental

A general formula correlating the bending curvature variation ratio of a layered structure caused by solvent-induced swelling in its polymer overcoat with diffusion time under case II diffusion has been presented. In the event of case II diffusion, the diffusion front velocity, v, can be calculated by using this formula and measured by a bending-beam apparatus. At room temperature, the diffusion of n-methyl-pyrrolidone (NMP) solvent in the film of pyromellitic phenylene diamine (PMDA-PDA) is case II. While in PMDA-B (-benzidine) and benzophenone tetracarboxylic dianhydride (BPDA-PDA), no diffusion progress can be observed. But, the diffusion in 6F-dianhydride- (6FDA-PDA) is case I with D = 0.85 × 10^?9 cm²/s. It becomes anomalous when mixing with 25% PMDA-B, but becomes case II diffusion with more PMDA-B. The preabsorbed moisture in the films does not affect the v value. In PMDA-PDA, v = 7.3 × 10^?8 cm/s. In the 25/75 and 50/50 6FDA-PDA/PMDA-B blends, v = 6.3 and 11.3 × 10^?8 cm/s.     

1-甲基-3-(7-氟-4-炔丙基-1,4-苯并噁嗪-3-酮-6-基)-1,3-喹唑啉-2,4-二酮的合成及其除草活性

标题化合物(SYP-298)是沈阳化工研究院的试验除草剂,由邻硝基苯甲酸经5步反应制得。其结构经核磁共振谱和质谱分析确证。SYP-298在温室条件下38 g a.i./hm2可防多种阔叶杂草,在600 g a.i./hm2对玉米和水稻安全。