Novel phosphorus-containing 17beta-side chain mifepristone analogues as progesterone receptor antagonists

A novel series of steroidal compounds were designed and synthesized with various phosphorus-containing groups on the 17beta-side chain as progesterone receptor antagonists. The structure-activity relationships of these compounds are discussed. Selected compounds were tested in an rat progesterone-sensitive assay. Some of these compounds are more potent than mifepristone, with a better selectivity profile in differentiating progesterone receptor from glucocorticoid receptor.     

A deletion at the mouse Xist gene exposes trans-effects that alter the heterochromatin of the inactive X chromosome and the replication time and DNA stability of both X chromosomes

The inactive X chromosome of female mammals displays several properties of heterochromatin including late replication, histone H4 hypoacetylation, histone H3 hypomethylation at lysine-4, and methylated CpG islands. We show that cre-Lox-mediated excision of 21 kb from both Xist alleles in female mouse fibroblasts led to the appearance of two histone modifications throughout the inactive X chromosome usually associated with euchromatin: histone H4 acetylation and histone H3 lysine-4 methylation. Despite these euchromatic properties, the inactive X chromosome was replicated even later in S phase than in wild-type female cells. Homozygosity for the deletion also caused regions of the active X chromosome that are associated with very high concentrations of LINE-1 elements to be replicated very late in S phase. Extreme late replication is a property of fragile sites and the 21-kb deletions destabilized the DNA of both X chromosomes, leading to deletions and translocations. This was accompanied by the phosphorylation of p53 at serine-15, an event that occurs in response to DNA damage, and the accumulation of gamma-H2AX, a histone involved in DNA repair, on the X chromosome. The Xist locus therefore maintains the DNA stability of both X chromosomes.     

Impaired development of broiler chickens by stress mimicked by corticosterone exposure

The effects of corticosterone (CORT) administration on the development of muscular tissues of broiler chickens (Gallus gallus domesticus) fed with diets differing in lipid content were investigated. The experimental chickens were given one of two experimental diets: high lipid diet (9.9% crude fat) or control diet, from 21 d of age. At 28 d of age, half of the chickens in each dietary treatment were exposed to CORT treatment, supplemented with 30 mg CORT/kg diet for 12 days, while the other half continued to consume the former diet. The zootechnical parameters were recorded at 21, 28, 35 and 39 d, and a blood sample was obtained from 8 birds of each group, respectively. The growth performance of broiler chickens was significantly depressed by CORT administration, but not by dietary treatment. Corticosterone treatment resulted in enhanced energy expenditure. The results indicate that the development of breast muscle was more susceptible to stress mimicked by CORT administration. The results suggest that corticosterone administration enhanced hepatic fatty acid synthesis and resulted in the redistribution of energy to abdominal store from peripheral tissues. Diet rich in lipid content was favorable to the central fat deposit in stressed broiler chickens.     

A New GA-Insensitive Semidwarf Mutant of Rice (Oryza sativa L.) with a Missense Mutation in the SDG Gene

A semidwarf line of Indica rice, Xinguiai, was derived from the progeny of a cross between the double dwarf mutant Xinguiaishuangai and the wild-type variety Nanjing 6. The semidwarf phenotype was controlled by the semidwarf gene, sdg. The second sheath and shoot elongation responses of the dwarf mutant to exogenous gibberellin (GA₃) showed that sdg was insensitive to gibberellin (GA), and its endogenous GAs content was higher than that in wild-type cultivars. The SDG gene was cloned by a map-based cloning method and sequencing analysis revealed that the coding region of sdg had a single nucleotide substitution resulting in a single amino acid change from alanine to threonine. A cleaved amplified polymorphic sequence marker was designed according to sequences from mutant and wild-type materials. This sequence marker could be used to distinguish wild types and mutants, and thus, could be used for molecular marker-assisted selection. The dwarf phenotype of the sdg mutant was restored to a normal phenotype by introducing the wild-type SDG gene. Rice transformation experiments and GUS staining demonstrated that the SDG gene was predominantly expressed in vegetative organs.     

Characterization of aflatoxigenic and non-aflatoxigenic <Emphasis Type="Italic">Aspergillus flavus</Emphasis> isolates from pistachio

Pistachio is a popular snack food. Aflatoxin contamination of pistachio nuts is a serious problem for many producing countries. The development of biological control methods based on ecological parameters is an environmentally friendly approach. Thirty-eight Aspergillus flavus isolates collected from a pistachio orchard in California (CA) were analyzed for production of aflatoxin (AF), cyclopiazonic acid (CPA), vegetative compatibility groups (VCGs), and mating types. All aflatoxigenic isolates produced both AFB₁ and CPA. The most toxigenic one was CA28 which produced 164 μg AFB₁ per 5 ml PDA fungal culture and small sclerotia (S strain, sclertoium size less than 400 μm). The other aflatoxigenic strains produce AFB₁ ranging from 1.2 μg to 80 μg per 5 ml fungal culture. Twenty-one percent of the CA isolates produced AFB₁, 84% produced CPA and half formed sclerotia on at least one of three tested media. The 38 CA isolates formed 26 VCGs, 6 of which had two or more isolates and 20 contained single isolates. The S strain isolates belong to 4 different VCGs. Genomic profiling by a retrotransposon DNA probe revealed fingerprint patterns that were highly polymorphic. The predicted VCGs (Pred-VCGs) based on a similarity coefficient >80% matched the VCGs of multiple isolates determined by complementation. All isolates within a VCG had the same mating-type gene of either MAT1-1 or MAT1-2. Uncorrected and VCG-corrected MAT1-1 and MAT1-2 among the isolates were equally distributed.     

Tumor progression: Chance and necessity in Darwinian and Lamarckian somatic (mutationless) evolution

Current investigation of cancer progression towards increasing malignancy focuses on the molecular pathways that produce the various cancerous traits of cells. Their acquisition is explained by the somatic mutation theory: tumor progression is the result of a neo-Darwinian evolution in the tissue. Herein cells are the units of selection. Random genetic mutations permanently affecting these pathways create malignant cell phenotypes that are selected for in the disturbed tissue. However, could it be that the capacity of the genome and its gene regulatory network to generate the vast diversity of cell types during development, i.e., to produce inheritable phenotypic changes without mutations, is harnessed by tumorigenesis to propel a directional change towards malignancy? Here we take an encompassing perspective, transcending the orthodoxy of molecular carcinogenesis and review mechanisms of somatic evolution beyond the Neo-Darwinian scheme. We discuss the central concept of "cancer attractors" - the hidden stable states of gene regulatory networks normally not occupied by cells. Noise-induced transitions into such attractors provide a source for randomness (chance) and regulatory constraints (necessity) in the acquisition of novel expression profiles that can be inherited across cell divisions, and hence, can be selected for. But attractors can also be reached in response to environmental signals - thus offering the possibility for inheriting acquired traits that can also be selected for. Therefore, we face the possibility of non-genetic (mutation-independent) equivalents to both Darwinian and Lamarckian evolution which may jointly explain the arrow of change pointing toward increasing malignancy.     

The inhibitory effect of a polysaccharide from Codonopsis pilosula on tumor growth and metastasis in vitro

In this study, we prepared an acidic polysaccharide (CPPA) from the roots of Codonopsis pilosula. The effects of CPPA on tumor cell growth, invasion, and migration were examined in vitro. The CPPA not only induced a potent inhibitory effect on the invasion and migration potential of human epithelial ovarian cancer HO-8910 cells in vitro, evaluated by wound healing, transwell and cell adhesion assays, but also had an efficient anti-proliferation effect on tumor cells. Moreover, the CD44 expression on the HO-8910 cells was also attenuated by CPPA treatment. Therefore, our results indicate that CPPA may be a potential candidate compound for the prevention of tumor metastasis, presumably by inhibiting invasion, migration and adhesion of tumor cells, as well as the CD44 expression on the tumor cells.     

Synergistic interactions between Glomus mosseae and Bradyrhizobium japonicum in enhancing proton release from nodules and hyphae

Soybean (Glycine max L. Merr.) seedlings were inoculated with Glomus mosseae (GM) and Bradyrhizobium japonicum (BJ) together or separately to study the effect of interactions on net H⁺ effluxes of nodules or extraradical hyphae by in vivo vibrating electrode techniques. GM promoted three-fold the H⁺ effluxes of nodules on mycorrhizal lateral roots and BJ increased eight-fold the net H⁺ effluxes of hyphae developing in the vicinity of nodules on lateral roots. Increments in plant P content were positively and linearly correlated with the net H⁺ efflux of nodules and hyphae. It is concluded that increased H⁺ effluxes of nodules resulted from enhanced nitrogenase activities induced by the presence of the AM fungus in lateral roots. The results point to additive effects of interactions between mycorrhizal fungi and rhizobia in increasing the extent of acidification of the “nodulesphere” and the hyposphere.     

Distinctive Mesorhizobium populations associated with Cicer arietinum L. in alkaline soils of Xinjiang, China

Background and aims

Rhizobia associated with chickpea in the main chickpea production zone of Xinjiang, China have never been investigated. Here, we present the first systematic investigation of these rhizobia’s genetic diversity and symbiotic interactions with their host plant.

Methods

Ninety-five isolates obtained from chickpea nodules in eight alkaline-saline (pH?8.24–8.45) sites in Xinjiang were characterized by nodulation test, symbiotic gene analysis, PCR-based restriction fragment length polymorphism (RFLP) of the 16S rRNA gene and 16S–23S rRNA intergenic spacer (IGS), BOX-PCR, phylogenies of 16S rRNA and housekeeping genes (atpD, recA and glnII), multilocus sequence analysis (MLSA) and DNA–DNA hybridization.

Results

All 95 isolates were identified within the genus of Mesorhizobium. Similarities less than 96.5% in MLSA and DNA–DNA hybridization values (<50%) between the new isolates and the defined Mesorhizobium species, and high similarities (>98%) of symbiotic genes (nodC and nifH) with those of the well studied chickpea microsymbioints Mesorhizobium ciceri and Mesorhizobium mediterraneum were found.

Conclusions

Chickpea rhizobia in alkaline-saline soils of Xinjiang, China, form a population distinct from the defined Mesorhizobium species. All these chickpea rhizobia in Xinjiang harbored symbiotic genes highly similar to the type strains of two well-studied chickpea rhizobia, M. ciceri and M. mediterraneum, evidencing the possible lateral transfer of symbiotic genes among these different rhizobial species. On the other hand, chickpea may strongly select rhizobia with a unique symbiotic gene background.