Phospholipid membrane stabilization by dimethylsulfoxide and other inducers of friend leukemic cell differentiation

A large number of low molecular weight polar cryoprotective agents have recently been found to induce erythroid differentiation of Friend leukemic cells in vitro. The effect of these agents on membrane fluidity in phospholipid vesicles was studied by determining the solid-to-liquid crystalline phase transition using differential scanning calorimetry. Some of the inducing agents studies were found to raise the normal transition temperature ($\text{T}{}_{\mathrm{<mtext>c</mtext>}}$ by a few degrees. All of these agents were found to produce a separate transition at a much higher temperature. Changes in the head group of the phospholipid, the pH, the presence of divalent cations, and the addition of other membrane-active compounds were found to significantly influence the inducing agent's effects on the $\text{T}{}_{\mathrm{<mtext>c</mtext>}}$ of phospholipid membranes.The ability of the different agents to produce a new transition at a high temperature was found to correlate well with their ability to incude Friend leukemic cell differentiation. The possible mechanisms of action of the chemical inducers, and the significance of the observed membrane effects on differentiation and malignancy are discussed. It is concluded that inducing agents decrease the fluidity and stabilize phospholipid membranes, and that their effects in cell differentiation might be initiated by a similar change in the properties of cell membranes.     

Expression of functional c-kit receptors rescues the genetic defect of W mutant mast cells.

Loss-of-function mutations in the gene for the c-kit tyrosine kinase receptor are strongly implicated in the developmental abnormalities of W mutant mice. To dissect further the relationship between kit and the W phenotype, retroviruses carrying the normal murine c-kit gene were constructed. In infected cells, the level of c-kit expression from these vectors varied markedly with different promoter elements, the 5' viral LTR proving to be the most effective. When introduced into cells which normally do not express c-kit, ectopic kit receptors transduced a ligand (Steel factor)-dependent proliferative signal in IL-3-dependent DA-1 myeloid cells and induced transformation in fibroblasts. Primary mutant mast cells were used to examine the effects of reconstituting functional kit expression in cells affected by W mutations. Exogenous c-kit expression rescued the defective proliferative response to Steel factor of cells from both W/Wv and W/W mutant mice. Moreover, functional kit expression also restored the capacity of W/Wv mast cells to survive and differentiate in vivo. These results imply that defective c-kit receptor function is sufficient to generate the W mutant phenotype.     

Volatile components of developing tomato fruit grown under field and greenhouse conditions

Volatile components of field- and glass greenhouse-grown tomatoes(Lycopersicon esculentum MILL., variety, V. R. Moscow) of differentmaturities were studied by gas-liquid and thin-layer chromatography.The following components were separated and identified: isobutylalcohol, isopentyl alcohol, hexyl alcohol, 2-methyl-3-hexanol,isovaleraldehyde, caproaldehyde, benzaldehyde, furfural, isopentylacetate, isopentyl butyrate, isopentyl isovalerate, butyl hexanoate,hexyl hexanoate, methyl salicylate and -pinene. Chromatogramswere consistent for both field- and greenhouse-grown tomatoesat all stages of maturity. Except for isovaleraldehyde and hexylalcohol, the biosynthesis of volatile components increased alongwith the growth of fruit. Isovaleraldehyde and hexyl alcohol,presumed to give the "green leafy" aroma of tomatoes, were foundto be in their highest concentrations at the breaker and thelarge-green stages, respectively. ¹This research was supported by a research grant—UI 00449—fromthe National Center for Urban and Industrial Health, U. S. PublicHealth Service.     

Vitamin A--a pregnancy hazard alert.

Vitamin A is essential to human health, but concerns have arisen recently regarding its potential teratogenicity. Human and animal birth defects have been associated with the use of the vitamin A analogue, isotretinoin, or Accutane, for acne treatment, although the association of such defects with vitamin A itself is unclear. The federal Food and Drug Administration is evaluating the health issues surrounding vitamin A and, together with the manufacturer, has developed restrictions and label warnings to ensure the appropriate use of Accutane. We also have evaluated these issues, with concerns about the possible teratogenicity of high vitamin A intake during pregnancy. Practitioners should be familiar with the possible hazard of excessive dosages of vitamin A and its analogues. Vitamin A daily doses of higher than 8,000 IU for pregnant woman are not necessary for good health and are not recommended. Foods high in beta-carotene can provide the necessary amounts of vitamin A and, in contrast to the synthetic analogues, their use has not been associated with vitamin A toxicity or teratogenicity in humans or animals.     

Effects of Single P-Element Insertions on Bristle Number and Viability in Drosophila Melanogaster

Single P-element mutagenesis was used to construct 1094 lines with P[lArB] inserts on all three major chromosomes in an isogenic background previously free of P elements. The effects of insertions on bristle number and on viability were assessed by comparison to 392 control lines. The variance and effects of P-element inserts on bristle number and viability were larger than those inferred from spontaneous mutations. The distributions of effects on bristle number were symmetrical and highly leptokurtic, such that a few inserts with large effects caused most of the increase in variance. The distribution of effects on viability were negatively skewed and platykurtic. On average, the effects of P-element insertions on bristle number were partly recessive and on viability were completely recessive. P-element inserts with large effects on bristle number tended to have reduced viability, but the correlation between the absolute value of the effects on bristle number and on viability was not strong. Fifty P-element inserts tagging quantitative trait loci (QTLs) with large effects on bristle number were mapped cytogenetically. Two P-element-induced scabrous alleles and five extramacrochaetae alleles were generated. Single P-element mutagenesis is a powerful method for identifying QTLs at the level of genetic locus.     

Polygenic Mutation in Drosophila Melanogaster: Estimates from Response to Selection of Inbred Strains

Replicated divergent artificial selection for abdominal and sternopleural bristle number from a highly inbred strain of Drosophila melanogaster resulted in an average divergence after 125 generations of selection of 12.0 abdominal and 8.2 sternopleural bristles from the accumulation of new mutations affecting bristle number. Responses to selection were highly asymmetrical, with greater responses for low abdominal and high sternopleural bristle numbers. Estimates of V(M), the mutational variance arising per generation, based on the infinitesimal model and averaged over the responses to the first 25 generations of selection, were 4.32 X 10(-3) V(E) for abdominal bristle number and 3.66 X 10(-3) V(E) for sternopleural bristle number, where V(E) is the environmental variance. Based on 10 generations of divergent selection within lines from generation 93, V(M) for abdominal bristle number was 6.75 X 10(-3) V(E) and for sternopleural bristle number was 5.31 X 10(-3) V(E). However, estimates of V(M) using the entire 125 generations of response to selection were lower and generally did not fit the infinitesimal model largely because the observed decelerating responses were not compatible with the predicted increasing genetic variance over time. These decelerating responses, periods of response in the opposite direction to artificial selection, and rapid responses to reverse selection all suggest new mutations affecting bristle number on average have deleterious effects on fitness. Commonly observed periods of accelerated responses followed by long periods of stasis suggest a leptokurtic distribution of mutational effects for bristles.     

Polygenic Mutation in Drosophila Melanogaster: Non-Linear Divergence among Unselected Strains

A highly inbred strain of Drosophila melanogaster was subdivided into 20 replicate sublines that were maintained independently with 10 pairs of randomly sampled parents per generation for 180 generations. The variance between lines in abdominal and sternopleural bristle number increased little after 100 generations, in contrast to the neutral expectation of a linear increase; and the covariances of line means between different generations declined with increasing number of generations apart, in contrast to the neutral expectation of constant covariance. Thus, under a neutral model, the estimates of mutational variance were lower than for previous estimates from the first 100 generations of subline divergence. An autoregressive model was fitted to the variance of line means that indicated strong natural selection. There is no single unequivocal explanation for the results. Possible and nonexclusive alternatives include stabilizing selection on bristle number and deleterious effects on fitness of bristle mutations. The inferred strengths of selection on both traits are too high for stabilizing selection alone, and the between-line variance did not continue to increase sufficiently for pleiotropy alone to account for the observations. A third potential explanation that does not invoke selection is duplicate epistasis between mutations affecting bristle number.