Crown-capped imidacloprid: A novel design and insecticidal activity

Imidacloprid (IMI) derivatives conjugated with benzo-15-crown-5 and benzo-18-crown-6 structures, applied for the first time to explore novel insecticidal molecule, elicited strong excitatory toxic signs to the house flies and stunningly exhibited three to five times higher insecticidal activity than that of the parent IMI, yet the two benzo-crown structures themselves had no effect.     

Synthesis and evaluation of 4-substituted benzylamine derivatives as beta-tryptase inhibitors

Since beta-tryptase is considered a critical mediator of asthma, potent tryptase inhibitors may be useful as new agents for the treatment of asthma. We investigated 4-substituted benzylamine derivatives and obtained M58539 (15h) as a potent inhibitor of beta-tryptase (IC50 = 5.0 nM) with high selectivity against other serine proteases, low molecular weight, clog P value less than 5, lack of amidino and guanidino groups, and independence of Zn2+ ion.     

Remarkable acceleration of a DNA/RNA inter-strand functionality transfer reaction to modify a cytosine residue: the proximity effect via complexation with a metal cation

Modified nucleosides in natural RNA molecules are essential for their functions. Non-natural nucleoside analogues have been introduced into RNA to manipulate its structure and function. We have recently developed a new strategy for the in situ modification of RNA based on the functionality transfer reaction between an oligodeoxynucleotide probe and an RNA substrate. 2′-Deoxy-6-thioguanosine (6-thio-dG) was used as the platform to anchor the transfer group. In this study, a pyridinyl vinyl ketone moiety was newly designed as the transfer group with the expectation that a metal cation would form a chelate complex with the pyridinyl-2-keto group. It was demonstrated that the (E)-pyridinyl vinyl keto group was efficiently and specifically transferred to the 4-amino group of the opposing cytosine in RNA in the presence of NiCl₂ with more than 200-fold accelerated rate compared with the previous system with the use of the diketo transfer group. Detailed mechanistic studies suggested that NiCl₂ forms a bridging complex between the pyridinyl keto moiety and the N7 of the purine residue neighboring the cytosine residue of the RNA substrate to bring the groups in close proximity.     

Wetting agent produced by Serratia marcescens

Abstract Serratia marcescens cultivated at 30°C was shown to produce a large amount of wetting agent, in contrast to bacteria cultivated at 37°C. The wetting agent, isolated by thin-layer chromatography was examined for surface activaties and was identified, by analysis of hydrolysates and methanolysates, and by infra-red and mass spectrometry, as an aminolipid identical to serratamolide.     

Transfer of Two Burkholderia and An Alcaligenes Species to Ralstonia Gen. Nov.

Based on the results of phenotypic characterization, cellular lipid and fatty acid analysis, phylogenetic analysis of 16S rDNA nucleotide sequences and rRNA-DNA hybridization, Burkholderia pickettii, Burkholderia solanacearum and Alcaligenes eutrophus are transferred to the new genus Ralstonia, and Ralstonia pickettii (Ralston, Palleroni and Doudoroff 1973) comb. nov., Ralstonia solanacearum (Smith 1896) comb, nov., and R. eutropha (Davis 1969) comb. nov. are proposed. The type species of the new genus is R. pickettii. Type strain of R. pickettii is ATCC 27511^T, of R. solanacearum is ATCC 10696^T, and of R. eutropha is ATCC 17697^T.     

Parallel antitumor,granuloma-forming and tumor-necrosis-factor-priming activities of mycoloyl glycolipids fromNocardia rubra that differ in carbohydrate moiety: Structure—activity relationships

Summary Multiple intravenous injections (30 µg, ten times) in ICR mice of trehalose dimycolate and glucose monomycolate fromNocardia rubra, containing C_36–48 mycolic acids, showed a prominent antitumor effect on a subcutaneously implanted sarcoma-180, an allogeneic sarcoma of mice with a significant granuloma formation in lungs, spleen and liver. On the other hand, mycoloyl glycolipids other than glucose monomycolate and trehalose dimycolate, such as mannose or fructose mycolate, showed no significant activity for tumor regression or granuloma formation in mice.Trehalose dimycolate and glucose monomycolate fromN. rubra, and glucose monomycolate with C_56–60 mycolic acids fromRhodococcus terrae also showed a distinctive priming activity for tumor necrosis factor (TNF), when lipopolysaccharide fromEscherichia coli was administered as an eliciting agent. The TNF activity in the sera of mice was abrogated almost completely by anti-(murine TNF) antibody with protein-A—agarose. Again in contrast, mannose and fructose mycolate fromN. rubra and glucose monomycolate with C_30–34 mycolic acids fromRhodococcus equi did not show such activities in mice.Meth-A, a syngeneic fibrosarcoma of BALB/c mice, was less sensitive to administration of glycolipids than sarcoma-180. These results indicated that the existence of a glucose or trehalose molecule was necessary for the expression of immunomodifying activities among various mycoloyl glycolipids differing in carbohydrate structure. However, since the administration of lipopolysaccharide was essentially required as an eliciting agent for the induction of TNF, while no eliciting agent was required for the antitumor activities, TNF does not seem to contribute directly to the antitumor activities of mycoloyl glycolipids in our systems. There was, however, a parallel structure-activity relationship among granuloma-forming, antitumor and TNF-priming activities, indicating that the structures of both the carbohydrate moiety and the mycoloyl residues influenced an initial step, such as macrophage activation, commonly and profoundly.     

Phospholipids of Nocardia coeliaca

The lipids of Nocardia coeliaca were separated into at least 10 components by the use of thin-layer chromatography. Phosphatidylcholine was the most abundant phospholipid in this organism, accounting for 25 to 40% of the total phospholipids. The major fatty acid components of the phosphatidylcholine were 14-methyl-pentadecanoic acid (41%), the other C(15) and C(17) iso- and anteiso-fatty acids (29%), and palmitic acid (13.5%). The next most abundant phospholipid was phosphatidylethanolamine (25 to 30%), followed by phosphatidylinositol (11 to 14%) and cardiolipin (7 to 15%). Phosphatidylethanolamine and phosphatidylinositol were very similar to the phosphatidylcholine in fatty acid composition, whereas cardiolipin was characterized by a higher content of palmitic acid (30%). In all of the phospholipids examined, only trace amounts of monounsaturated fatty acids were present. When washed cells of N. coeliaca were incubated with methionine-methyl-(14)C for 1 to 3 hr, the radioactivity was mainly incorporated into the choline moiety of the phosphatidylcholine. In contrast, acetate-1-(14)C or glycerol-1-(14)C was incorporated much more slowly into the phosphatidylcholine than into the other phospholipids and neutral lipids. No phosphatidylcholine was detected in 10 other species of Nocardia examined.     

Molecular Nature of Spontaneous Mutations in Mouse Lactate Dehydrogenase-a Processed Pseudogenes

The presence of at least ten mouse LDH-A pseudogenes was demonstrated in the genomic blot analysis, and four different processed pseudogenes have thus far been isolated and characterized. In this report, the nucleotide sequences to two different mouse lactate dehydrogenase-A processed pseudogenes, M11 and M14, were determined and compared with the protein-coding sequences of the mouse and rat LDH-A functional genes. In the pseudogene M11, the sequence of 64 nucleotides from codon no. 257 to 278 was tandemly duplicated. In the pseudogene M14, the sequence of 22 nucleotides from codon no. 68 to 75 was replaced by an inserted repetitive sequence of 242 nucleotides homologous to a mouse truncated R element. The pattern of nucleotide substitutions accumulated in mouse LDH-A pseudogenes M11 and M14, as well as that of pseudogene M10 identified previously, was analyzed, and the substitution frequencies of the C or G at the CG dinucleotide were found to be high.     

Relationship Between [3H]Mazindol Binding to Dopamine Uptake Sites and [3H]Dopamine Uptake in Rat Striatum During Aging

Certain drugs exhibit a remarkable correlation between their ability to inhibit synaptosomal uptake of dopamine and the binding of [3H]mazindol to striatal membranes. To investigate the role of mazindol binding sites in the dopamine uptake process and the fate of these sites (labeling dopaminergic neurons) during aging, we have examined the properties of mazindol binding and dopamine uptake in individual young and old rats. There was a 48% decrease (p = 0.0001) in the Bmax of mazindol binding and a 23% decrease (p = 0.0166) in the Vmax of dopamine uptake with no apparent change in their affinities with age. Regression analysis of the relationship between Bmax and Vmax exhibited a significant correlation in old (p = 0.0156) but not young rats (p = 0.1398). These data suggest that the number of mazindol binding sites decreases with age and that the number of sites on the dopamine transporter complex far exceeds the number required to elicit maximal dopamine uptake.     

Clonal heterogeneity of thymic muscle-cell precursors

Three myoid-cell clones were established from the thymuses of two Wistar rats; one thymus yielded two clones, RBISA and R615B2, and the other yielded one clone, R613Ad. The three clones were divided into two subtypes. Both subtypes were able to form myofibrils, expressed AChR on their cell-surface membrane, and contained myofibrillar ATPase characteristic of und ifferentiated type-2C fibers, but they differed from each other in morphology, expression of Thy 1 antigen, spontaneous contractility, and qualitative accumulation of AChR. Immunolocalization studies using antisera against the respective cell subtypes also indicated regional differences in their cellular origin. These results show that the thymus contains heterogenous myoid-cell precursors.