Inhibition of DNA Synthesis but not of Poly-dAT Synthesis by the Arabinose Analogue of Cytidine <Emphasis Type="Italic">in vitro</Emphasis>

Kimball and Wilson¹ reported that the arabinose analogue of cytidine (ara-C) inhibited DNA polymerase in a crude extract prepared from Ehrlich ascites cells. Furth and Cohen² observed cytosine arabinoside triphosphate (ara-CTP) inhibited DNA polymerase in extracts from either calf thymus or bovine lymphosarcoma tissue, although these investigators³ had already found no effect of ara-CTP on DNA polymerase from Escherichia coli. The inhibition in both of these cases could be substantially reversed by dCTP; but incorporation of the arabinose nucleotide (ara-CMP) into DNA could not be unequivocally demonstrated. Graham and Whitmore⁴ reported the incorporation of ara-C into DNA in vivo and the inhibition of a DNA polymerase from L cells by ara-CTP. They found that ara-CMP was initially incorporated into small DNA strands but subsequently appeared in long strands. Momparler⁵ has presented evidence that, in vitro, ara-C incorporation was limited to the 3′-hydroxyl end of DNA chains. Such incorporation might be expected to block further chain elongation but this expectation was not supported by the evidence presented by Graham and Whitmore.     

Endopeptidase Activity of Phage λ-Endolysin

JACOB and Fuerst^1,2 demonstrated the presence of a bacteriolytic enzyme (λ-endolysin) in the induced cultures of lysogenic Escherichia coli K12 (λ). The enzyme was later identified as the product of gene R; of phage λ³ which is involved in bacterial lysis at the end of a latent period. The enzyme is apt to form spheroplast-like structures in E. coli² and one would therefore expect its substrate to be murein.     

Effect of vitamin on 2-deoxy-d-glucose uptake in human fibroblast cultures

Summary 2-Deoxy-d-glucose (2-DOG) uptake was tested in human fibroblast cultures in the presence and absence of vitamin E. Addition of 10 μg/ml vitamin E to the culture medium significantly reduced this uptake for 2-DOG concentrations of 0.005, to 10 mmol/liter (P≤0.01). The decrease of 2-DOG uptake was inversely proportional to the rise in 2-DOG concentration (P≤0.01). The presence of vitamin E reduced by 71% the average cellular level of lipid peroxides (expressed as thiobarbituric acid reactive substances) and caused a small but significant decrease in the cholesterol concentration (P≤0.01). These last results might explain the decrease in 2-DOG uptake observed in the presence of vitamin E.     

Diurnal variation of corticotropin-releasing factor binding sites in the rat brain and pituitary

Summary 1. Corticotropin-releasing factor (CRF) is thought to be involved in the regulation of the diurnal activity of the hypothalamus-pituitary-adrenal (HPA) axis and to act as a neurotransmitter in the brain. To date it is unknown whether the binding sites of the central CRF system are subject to diurnal variations. 2. We measured the number of CRF binding sites over the course of a complete 24-hr light-dark cycle in the pituitary, amygdala, bed nucleus of the stria terminalis (BNST), cingulate cortex, visceral cortex, paraventricular nucleus of the hypothalamus, hippocampus, and locus ceruleus of rats byin vitro receptor autoradiography with iodinated ovine CRF. A 24-hr time course was also established for plasma CRF and corticosterone. 3. The diurnal pattern of plasma CRF does not correlate with the pattern of plasma corticosterone. Within the brain, CRF binding in the basolateral nucleus of the amygdala showed a U-shaped curve with maximum levels in the morning and a wide hallow between 1500 and 0100. A biphasic profile with a small depression in the afternoon and a more pronounced depression in the second half of the activity period is characteristic for the other brain areas and the pituitary. The profile for the pituitary correlates with those for the BNST and the area of the locus ceruleus. Furthermore, the diurnal pattern of CRF binding sites in the BNST correlates with that of the hippocampus, and the daytime pattern of the visceral cortex is similar to that of both the hippocampus and the BNST. 4. Since the CRF-binding profiles in the brain and the pituitary clearly differ from the profiles of both plasma CRF and corticosterone, one may assume that the diurnal pattern of central CRF binding sites is not directly coupled to the activity of the HPA axis.     

Fluorescence studies using synchrotron radiation on normal and differentiated cells labeled with parinaric acids

Changes in membrane properties during the differentiation process in K562 cells have been investigated. A decrease of lectin-induced agglutination has been detected. The agglutination assay revealed to be an early and sensitive test to monitor the induced differentiation of the K562 cells. Naturally occurring fluorescent fatty acids (cis- and trans-parinaric acids) and the recently developed multifrequency phase and modulation technique were used to study cell membrane properties. Changes in fluorescence lifetime and polarization are clearly associated with cell differentiation, suggesting the involvement of the cellular plasma membrane in the differentiation process.     

The gene in search of an identity

Summary The concept of the difference between the potential for a trait and the trait proper, i.e., between the genotype and the phenotype, became clear only during the first decade of the century, mainly through the work of Johannsen. Although Johannsen insisted on that the terms he coined were only helpful devices to organize data about heredity, it is obvious that they were bound from the beginning to the hypothesis that there was something in the gametes that could be rendered to analysis as discrete units. These units were the genes.This reductionist yet materially non-committed attitude has been developed into what I called instrumental-reductionism: the genes were hypothetical constructs that were accepted as if they were real entities. The research program developed on such a concept was very successful, not least because this instrumental approach allowed maximum flexibility in the attachment of meaning of the genes. While most geneticists accepted one or another position of this flexible concept, others took more extreme positions. At the one extreme end of the conceptual continuum was the realist approach that argued that genes were discrete, measurable, material particles, and on the other end, the claim that the attempts to identify discrete units only led to hyperatomism of a holistic view appropriate to heredity.The acceptance of the gene as a material and discrete unit, in the beginning of 1950s, opened the way to a deeper level of conceptualizing both its structure (cistron-recon-muton) and function (one gene—one enzyme). The discovery of the structure of DNA finally offered a chemical-physical explanation to the geneticist's requirements of a material gene. Thus, within less than 20 years the gene has been established as a sharply limited segment of the linear structure that is involved in the structrue of a product or its regulation.However, with turning of much of the attention to the eucaryotic DNA, it was necessary to accommodate the gene to an increasing flood of findings that did not tally with its concept as a discrete material unit. Without much heart-seeking among geneticists, the gene regained its role as an instrumental unit, or even as just an intervening variable, a quantity obtained by specified manipulation of the values of empirical variables. Though this flexibility demonstrated again that the most fruitful concepts are those to which it is impossible to attach a well defined meaning, it brought us also into a situation in which the same term has a different meaning for each group of scientists. In order to avoid the danger to be scattered over the face of all the earth because of lack of communicable language, it might be advisable to halt a little and reflect on the meaning of our concepts and their function.     

Ultrastructural changes during encystment and germination of Bdellovibrio sp.

Under proper conditions, Bdellovibrio sp. strain W cells develop into bdellocysts in appropriate prey bacteria. After attachment and penetration of the prey cell, the encysting bdellovibrio began to accumulate inclusion material and increase in size, and was surrounded by an outer layer of amorphous electrondense material. The cytoplasm of the encysting cell appeared more electron dense, and nuclear areas appeared more compact. During germination of bdellocysts, the outer wall was uniformly broken down the inclusion material changed shape and affinity for the heavy metal stain, and the nuclear areas expanded. As the outer wall was dissolved, outgrowth began with the elongation of the germinant as it emerged from the prey ghost as an actively motile cell.