Relationship between histology,development and tumorigenesis of mammary gland in female rat

The mammary gland is a dynamic organ that undergoes structural and functional changes associated with growth, reproduction, and post-menopausal regression. The postnatal transformations of the epithelium and stromal cells of the mammary gland may contribute to its susceptibility to carcinogenesis. The increased cancer incidence in mammary glands of humans and similarly of rodents in association with their development is believed to be partly explained by proliferative activity together with lesser degree of differentiation, but it is not completely understood how the virgin gland retains its higher susceptibility to carcinogenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer. An early first full-term pregnancy may have a protective effect. Rodent models are useful for investigating potential breast carcinogens. The purpose of this review is to help recognizing histological appearance of the epithelium and the stroma of the normal mammary gland in rats, and throughout its development in relation to tumorigenic potential.     

Genetic diversity patterns in Curcuma reflect differences in genome size

The relationships between genome size and the systematic and evolutionary patterns in vascular plants are equivocal, although a close relationship between genome size and evolutionary patterns has been previously reported. However, several studies have also revealed the dynamic nature of genome size evolution and its considerable ‘ups’ and ‘downs’. Thus, in this study, the phylogenetic relationships among three previously revealed genome size groups and among species of the highly polyploid genus Curcuma were evaluated using AFLP. Our results suggest two main lineages within Indian Curcuma reflecting evolution of genome size. The first one includes hexaploids and higher polyploids of the previously recognized genome size group I, and the second one includes mainly hexaploids of genome size groups II and III. Within genome size group I, relationships among species seem to be influenced by reticulate evolution and higher polyploids are likely to be of allopolyploid origin. Reproductive systems in Indian Curcuma vary considerably among ploidy levels and these differences considerably affect morphological and genetic variation. In general, clonally reproducing species are expected to exhibit low genotypic diversity, but, at the same time, species of allopolyploid origin are expected to maintain higher levels of heterozygosity compared with their progenitors. We investigated intra‐populational genetic variability in Curcuma spp. to evaluate whether mode of reproduction or ploidy represent the main factor influencing the degree of genetic diversity. We found that hexaploid species exhibited significantly higher genetic diversity than higher polyploids (9x, 15x). Our results suggest that this genetic diversity pattern is largely influenced by the mode of reproduction, as higher polyploids reproduce exclusively vegetatively, whereas hexaploids reproduce mainly sexually. © 2011 The Linnean Society of London, Botanical Journal of the Linnean Society, 2011, 165 , 388–401.     

Optimization of Benzoisothiazole dioxide inhibitory activity of the NS5B polymerase of HCV genotype 4 using ligand-steered homological modeling, reaction-driven scaffold-hopping and Enovo workflow

Infection caused by hepatitis C virus (HCV) is a significant world health problem for which novel therapies are in urgent demand. The virus is highly prevalent in the Middle East and Africa particularly Egypt with more than 90% of infections due to genotype 4. Nonstructural (NS5B) viral proteins have emerged as an attractive target for HCV antivirals discovery. A potent class of inhibitors having benzisothiazole dioxide scaffold has been identified on this target, however they were mainly active on genotype 1 while exhibiting much lowered activity on other genotypes due to the high degree of mutation of its binding site. Based on this fact, we employed a novel strategy to optimize this class on genotype 4. This strategy depends on using a refined ligand-steered homological model of this genotype to study the mutation binding energies of the binding site amino acid residues, the essential features for interaction and provide a structure-based pharmacophore model that can aid optimization. This model was applied on a focused library which was generated using a reaction-driven scaffold-hopping strategy. The hits retrieved were subjected to Enovo pipeline pilot optimization workflow that employs R-group enumeration, core-constrained protein docking using modified CDOCKER and finally ranking of poses using an accurate molecular mechanics generalized Born with surface area method.     

Prospecting the utility of a PMI/mannose selection system for the recovery of transgenic sugarcane (<Emphasis Type="Italic">Saccharum</Emphasis> spp. hybrid) plants

For the first time, the phosphomannose isomerase (PMI, EC 5.3.1.8)/mannose-based “positive” selection system has been used to obtain genetically engineered sugarcane (Saccharum spp. hybrid var. CP72-2086) plants. Transgenic lines of sugarcane were obtained following biolistic transformation of embryogenic callus with an untranslatable sugarcane mosaic virus (SCMV) strain E coat protein (CP) gene and the Escherichia coli PMI gene manA, as the selectable marker gene. Postbombardment, transgenic callus was selectively proliferated on modified MS medium containing 13.6 μM 2,4-D, 20 g l⁻¹ sucrose and 3 g l⁻¹ mannose. Plant regeneration was obtained on MS basal medium with 2.5 μM TDZ under similar selection conditions, and the regenerants rooted on MS basal medium with 19.7 μM IBA, 20 g l⁻¹ sucrose, and 1.5 g l⁻¹ mannose. An increase in mannose concentration from permissive (1.5 g l⁻¹) to selective (3 g l⁻¹) conditions after 3 weeks improved the overall transformation efficiency by reducing the number of selection escapes. Thirty-four vigorously growing putative transgenic plants were successfully transplanted into the greenhouse. PCR and Southern blot analyses showed that 19 plants were manA-positive and 15 plants were CP-positive, while 13 independent transgenics contained both transgenes. Expression of manA in the transgenic plants was evaluated using a chlorophenol red assay and enzymatic analysis.     

Acute toxicity and adverse effects of aqueous and ethanol extracts of Parkia biglobosa pods on biochemical parameters of Clarias gariepinus

The acute toxicity of the aqueous and ethanol extracts of Parkia biglobosa pods against Clarias gariepinus was investigated under laboratory conditions. Agitated behaviours and respiratory distress were also observed during the exposure period. The adverse effects on biochemical parameters were assessed using semi-static bioassays for 28 days. The ethanol extract of P. biglobosa pods was found to be more acutely toxic with a 96 h LC₅₀ value of 13.96 mg l^?1 than the aqueous extracts, with a 96 h LC₅₀ value of 19.95 mg l^?1 against C. gariepinus. Both extracts induced agitated behaviours and respiratory distress in exposed organisms. The activities of superoxide dismutase (SOD), catalase (CAT) and the concentration of malondialdehyde (MDA) were significantly lower (p < 0.05) in groups of organisms exposed to extracts of P. biglobosa when compared with the control group after 14 days. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were also significantly (p < 0.05) lower compared with activities of the enzymes in the control group after 28 days. The current study has shown that the introduction of P. biglobosa pods into aquatic ecosystems is acutely toxic to fish and would possibly be to other non-target aquatic organisms especially invertebrates.     

A genome-wide collection of Mos1 transposon insertion mutants for the C. elegans research community

Methods that use homologous recombination to engineer the genome of C. elegans commonly use strains carrying specific insertions of the heterologous transposon Mos1. A large collection of known Mos1 insertion alleles would therefore be of general interest to the C. elegans research community. We describe here the optimization of a semi-automated methodology for the construction of a substantial collection of Mos1 insertion mutant strains. At peak production, more than 5,000 strains were generated per month. These strains were then subject to molecular analysis, and more than 13,300 Mos1 insertions characterized. In addition to targeting directly more than 4,700 genes, these alleles represent the potential starting point for the engineered deletion of essentially all C. elegans genes and the modification of more than 40% of them. This collection of mutants, generated under the auspices of the European NEMAGENETAG consortium, is publicly available and represents an important research resource.