Ribosomal protein S6 gene haploinsufficiency is associated with activation of a p53-dependent checkpoint during gastrulation

Nascent ribosome biogenesis is required during cell growth. To gain insight into the importance of this process during mouse oogenesis and embryonic development, we deleted one allele of the ribosomal protein S6 gene in growing oocytes and generated S6-heterozygous embryos. Oogenesis and embryonic development until embryonic day 5.5 (E5.5) were normal. However, inhibition of entry into M phase of the cell cycle and apoptosis became evident post-E5.5 and led to perigastrulation lethality. Genetic inactivation of p53 bypassed this checkpoint and prolonged development until E12.5, when the embryos died, showing decreased expression of D-type cyclins, diminished fetal liver erythropoiesis, and placental defects. Thus, a p53-dependent checkpoint is activated during gastrulation in response to ribosome insufficiency to prevent improper execution of the developmental program.     

The influence of vitamin C supplementation on the oxidative status of rat interscapular brown adipose tissue

The interscapular brown adipose tissue (IBAT) thermogenesis is accompanied with oxidative stress. In spite of the ability of rats to synthesize vitamin C, we tested the possibility that its additional intake may improve the tissue antioxidative protection. Thus, we studied the IBAT oxidative status in rats supplemented by two doses of ascorbic acid over a 4-week period of time.

Our results confirmed that the additional intake of ascorbate improves the tissue antioxidative defense. Probably acting through enhanced insulin release, vitamin C also exerted some metabolic effects, which emphasize its role in the regulation of IBAT functions under normal physiological conditions.     

Synthesis, cytostatic and anti-HIV evaluations of the new unsaturated acyclic C-5 pyrimidine nucleoside analogues

A series of the novel C-5 alkynyl pyrimidine nucleoside analogues (1-14) in which the sugar moiety was replaced by the conformationally restricted Z- and E-2-butenyl spacer between the phthalimido and pyrimidine ring were synthesized by using Sonogashira cross-coupling reaction. Cytostatic activity evaluation of the novel compounds showed that E-isomers exhibited, in general, better cytostatic activities than the corresponding Z-isomers. E-isomer 14 exhibited the best cytostatic effect against all evaluated malignant cell lines, particularly against hepatocellular carcinoma (Hep G2, IC(50)=4.3microM). However, this compound was also cytotoxic to human normal fibroblasts (WI 38). Its Z-isomer 7 showed highly specific antiproliferative activity against Hep G2 (IC(50)=18microM) and no cytotoxicity to WI 38. Moreover, compounds 3, 4 and 14 expressed some marginal inhibitory activity against HIV-1 and HIV-2.     

Effects of adrenalectomy and hydrocortisone on DNA synthesis in the rat anterior pituitary gland

The effect of adrenalectomy and hydrocortisone on /³H/-thymidine uptake by rat anterior pituitary cells in the short-time organ culture was investigated. Adrenalectomy significantly increases the incorporation tritiated thymidine into anterior pituitary cells nuclei, whereas hydrocortisone has an opposit effect. The existence on negative feedback between the intracellular hormone content and DNA synthesis in ACTH-secreting anterior pituitary cells is suggested.     

Influence of pinealectomy on the mitotic activity of regenerating adrenal cortex in rats

There is some evidence that the pineal gland may influence the proliferation of both normal and neoplastic cells. The adrenal cortex has very high capacity for regeneration. Therefore, the effects of pinealectomy on the mitotic activity of regenerating adrenal cortex of rats were studied on the second, seventh and twelfth days following the enucleation of adrenals. Pinealectomy caused a significant decrease in the mitotic index of regenerating adrenal cortex after 2 and 12 days in comparison to sham operated controls.     

Some characteristics of a factor stimulating skin epithelial cell growth in vitro

Growth of rabbit skin epithelial cells on a collagen gel is markedly enhanced by a soluble factor synthesized in a chemically defined minimal growth medium by fibroblasts of dermal origin. In the presence of this factor, the incorporation of thymidine and phosphate into skin epithelial cells is stimulated, and survival time of skin epithelial cells is prolonged. The growth factor is small (mol.wt < 1 000 D) and is not sensitive to lyophilization, heating, repeated freezing and thawing or the action of degradative enzymes RNAse, DNAse, trypsin and pronase. The chemical properties of the growth factor are not those expected of a free amino acid, peptide, non-polar lipid or nucleic acid.     

Production of biomass, carotenoid and other lipid metabolites by several red yeast strains cultivated on waste glycerol from biofuel production – a comparative screening study

This study was focused on a comparison of growth and production properties of seven red yeast strains of the genus Rhodotorula, Sporobolomyces and Cystofilobasidium cultivated on glycerol substrate. Production of enriched yeast biomas and specific yeast metabolites (carotenoids, ergosterol, lipids) was evaluated on medium with glucose, pure technical glycerol and/or waste glycerol from biofuel production (40 g/L) and mixture of glycerol and glucose (1:3, 1:1, 3:1; C/N ratio 57 in all cultivations). All tested strains were able to utilize glycerol as the only carbon source. Production of biomass on waste glycerol was in most strains higher than in control as well as in medium with pure technical glycerol and reached 15.97–21.76 g/L. Production of carotenoids and ergosterol was better in glucose medium than in medium with glycerol only. Nevertheless, using glycerol medium with addition of glucose, higher yields of total carotenoids, beta-carotene and ergosterol were obtained than in control. The highest yields of total pigments were reached by Sporobolomyces roseus (3.60 mg/g cell dry weight (CDW); glycerol:glucose 1:3), Sporobolomyces salmonicolor (2.85 mg/g CDW; glycerol:glucose 1:3) and Rhodotorula glutinis (2.80 mg/g CDW; glycerol:glucose 3:1) In glucose medium, most tested strains except Cystofilobasidium capitatum (22.6 %) produced neutral lipids in the range of 11–15 %. Production of triacylglycerols in all strains was in 10–30 % better in glycerol medium, in which Rhodotorula aurantiaca and Sporobolomyces shibatanus also reached intracellular triacylglycerol concentrations up to 20 % of biomass. This study has shown that oleaginous red yeasts could have great potential for converting crude glycerol to valuable lipids and carotenoids in respect of efficient bioresources utilization.