Inhibition of the estrogen-induced synthesis of vitellogenin mRNA in chick liver by tamoxifen

Cloned vitellogenin cDNA (labelled with ³²P) was used as a probe for measuring vitellogenin mRNA sequences in RNA preparations from the liver of chicks treated with estradiol and/or tamoxifen. For the first time it was shown that the antiestrogen tamoxifen inhibits the estradiol-induced synthesis of vitellogenin mRNA in chick liver. This inhibition correlates very well with a reduced capacity of the liver to synthesize vitellogenin. Furthermore, evidence is presented that tamoxifen lacks any agonistic activity in chick liver. Vitellogenin mRNA is not measurable after tamoxifen alone.     

复合氨基酸铁铵的药效学及毒理学研究

利用少量多次放血法,制备家兔失血性贫血模型,观察复合氨基酸铁铵的抗贫血作用。对贫血家兔连续给药９天,本品的高、低剂量组和硫酸亚铁组,在提高血红蛋白,红细胞数以及红细胞比积方面与生理盐水组相比较具显著的统计学意义。急性毒性实验表明本品的ＬＤ５０为２．９２５ｇ／ｋｇ。     

Fimbrial adhesins: similarities and variations in structure and biogenesis

Abstract Fimbriae are wiry (2 to 4 nm diam.) or rod-shaped (6 to 8 nm diam.), fibre-like structures on the surfaces of bacteria which mediate attachment to host cells. Much has been learned in recent years about the biogenesis, structure and regulation of expression of these adhesive organelles in Gram-negative bacteria. Analyses of the genetic determinants encoding the biogenesis of fimbriae has revealed that the adhesive interaction of fimbriae can be mediated by major subunits (CFA/I and CS1 fimbriae) or minor subunits (P, S, and type 1 fimbriae), with the adhesin being located either at the tip of the fimbria or along the length of the fimbrial shaft. Minor subunits can also act as adapters, anchors, initiators or elongators. Post-translational glycosylation of the type 4 pilins of Neisseria gonorrhoeae, Neisseria meningitidis and Pseudomonas aeruginosa has been demonstrated. The structures of the PapD chaperone of Escherichia coli and of N. gonorrhoeae type 4 fimbrin have been resolved at 2.0–2.6 Å. Rod-shaped fimbriae should not be thought of as being rigid inflexible structures but rather as dynamic structures which can undergo transition from a helicoidal to a fibrillar conformation to provide a degree of elasticity and plasticity to the fimbriae so that they can resist shear forces, rather like a bungee cord. At least four mechanisms have been identified in the assembly of fimbriae from fimbrin subunits, namely the chaperone-usher pathway (e.g., P-fimbriae of uropathogenic E. coli ), the general secretion assembly pathway (e.g., type 4 fimbriae or N -methylphenylalanine fimbriae of P. aeruginosa , the extracellular nucleation-precipitation pathway (e.g., curli of E. coli ) and the CFA/I, CS1 and CS2 fimbrial pathway.     

Inverted Configural Types Derived from Incomplete Contingency Tables: Q-CFA

Inverted Configural Frequency Analysis (Q-CFA) allows one to analyze complete and incomplete, symmetrical and asymmetrical cross-classifications made up by individuals rather than variables. The cells of such cross-classifications contain counts of behavior events as, for instance, pairwise interactions of individuals. The paper introduces Q-CFA. Interactions between individuals are defined as dyadic types and antitypes or as monadic types and antitypes. An example is given using data that describe genital display frequencies in squirrel monkeys. Generalizations are discussed in regard to the number of groups of individuals involved, to the type of design used for data collection, and the number of variables simultaneously analyzed.     

Enhancing activity of N-glycosylation for constitutive proteins secretions in non-polarized cells

Several fusion proteins of mouse Interleukins (mILs) and the enhanced green fluorescent protein (EGFP) were expressed in fibroblast and epithelial cells. Among these proteins, the mIL-31 derivative was the most efficiently secreted into the medium in a N-glycosylation-dependent manner. From the analysis of deletion mutants, the minimal structure for constitutive secretions consisted of a signal peptide and N-glycosylation. Introduction of the signal sequence from mIL-31 to human p53 protein failed to secrete the products, but further addition of the N-glycosylation site resulted in constitutive secretion of biologically active p53 protein into the medium in the N-glycosylated form. In this report, we showed the importance of N-glycosylation for constitutive protein secretions, especially using non-polarized cells.     

UPLC/MS based method for quantitative determination of fatty acid composition in Gram-negative and Gram-positive bacteria

Quantitative fatty acid composition of microorganisms at various growth space points is required for understanding membrane associated processes of cells, but the majority of the relevant publications still restrict to the relative compositions. In the current study, a simple and reliable method for quantitative measurement of fatty acid content in bacterial biomass without prior derivatization using ultra performance liquid chromatography-electrospray ionization mass spectrometry was developed. The method was applied for investigating the influence of specific growth rate and pH on the fatty acid profiles of two biotechnologically important microorganisms — Gram-negative bacteria Escherichia coli and Gram-positive bacteria Lactococcus lactis grown in controlled physiological states. It was found that the membranes of slowly growing cells are more rigid and that the fatty acid fraction of the cells of L. lactis diminishes considerably with increasing growth rate.     

Discovery of novel spirocyclic inhibitors of fatty acid amide hydrolase (FAAH). Part 2. Discovery of 7-azaspiro[3.5]nonane urea PF-04862853, an orally efficacious inhibitor of fatty acid amide hydrolase (FAAH) for pain

Fatty acid amide hydrolase (FAAH) is an integral membrane serine hydrolase responsible for the degradation of fatty acid amide signaling molecules such as endocannabinoid anandamide (AEA), which has been shown to possess cannabinoid-like analgesic properties. Herein we report the optimization of spirocyclic 7-azaspiro[3.5]nonane and 1-oxa-8-azaspiro[4.5]decane urea covalent inhibitors of FAAH. Using an iterative design and optimization strategy, lead compounds were identified with a remarkable reduction in molecular weight and favorable CNS drug like properties. 3,4-Dimethylisoxazole and 1-methyltetrazole were identified as superior urea moieties for this inhibitor class. A dual purpose in vivo efficacy and pharmacokinetic screen was designed to be the key decision enabling experiment affording the ability to move quickly from compound synthesis to selection of preclinical candidates. On the basis of the remarkable potency, selectivity, pharmacokinetic properties and in vivo efficacy, PF-04862853 (15p) was advanced as a clinical candidate.     

Corynebacterium aquatimens sp. nov., a lipophilic Corynebacterium isolated from blood cultures of a patient with bacteremia

An unknown lipophilic coryneform bacterium isolated from the blood cultures of a patient with bacteremia was characterized by phenotypic and molecular genetic methods. Chemical analysis revealed the presence of short chain mycolic acids consistent with the genus Corynebacterium. The DNA G+C content was 60.8mol%. Comparative 16S rRNA gene sequence analysis demonstrated that the isolate represents a new subline within the genus Corynebacterium. The closely phylogenetic relative of the unknown bacterium was found to be C. tuscaniense (97.8% sequence similarity). Partial rpoB gene sequence revealed that strain IMMIB L-2475(T) exhibited 13.5% sequence divergence with C. tuscaniense. The unknown bacterium was distinguished from C. tuscaniense by, DNA-DNA hybridization, cellular fatty acid profiles, MALDI-TOF analyses of cell extracts and biochemical tests. Based on the phylogenetic and phenotypic criteria, it is proposed that this bacterium be classified as new species, Corynebacterium aquatimens sp. nov., and is represented by strain IMMIB L-2475(T) (=DSM 45632(T)=CCUG 61574(T)).