Zebra fish myc family and max genes: differential expression and oncogenic activity throughout vertebrate evolution.

To gain insight into the role of Myc family oncoproteins and their associated protein Max in vertebrate growth and development, we sought to identify homologs in the zebra fish (Brachydanio rerio). A combination of a polymerase chain reaction-based cloning strategy and low-stringency hybridization screening allowed for the isolation of zebra fish c-, N-, and L-myc and max genes; subsequent structural characterization showed a high degree of conservation in regions that encode motifs of known functional significance. On the functional level, zebra fish Max, like its mammalian counterpart, served to suppress the transformation activity of mouse c-Myc in rat embryo fibroblasts. In addition, the zebra fish c-myc gene proved capable of cooperating with an activated H-ras to effect the malignant transformation of mammalian cells, albeit with diminished potency compared with mouse c-myc. With respect to their roles in normal developing tissues, the differential temporal and spatial patterns of steady-state mRNA expression observed for each zebra fish myc family member suggest unique functions for L-myc in early embryogenesis, for N-myc in establishment and growth of early organ systems, and for c-myc in increasingly differentiated tissues. Furthermore, significant alterations in the steady-state expression of zebra fish myc family genes concomitant with relatively constant max expression support the emerging model of regulation of Myc function in cellular growth and differentiation.     

Current allele distribution of the human longevity gene APOE in Europe can mainly be explained by ancient admixture

Variation in apolipoprotein E (APOE) has been shown to have the strongest genetic effect on human longevity. The aim of this study was to unravel the evolutionary history of the three major APOE alleles in Europe by analysing ancient samples up to 12,000 years old. We detected significant allele frequency shifts between populations and over time. Our analyses indicated that selection led to large frequency differences between the earliest European populations (i.e., hunter-gatherers vs. first farmers), possibly due to changes in diet/lifestyle. In contrast, the allele distributions in populations from ~4000 BCE onward can mainly be explained by admixture, suggesting that it also played an important role in shaping current APOE variation. In any case, the resulting allele frequencies strongly influence the predisposition for longevity today, likely as a consequence of past adaptations and demographic processes.     

Behavioral assessment of the ability of intracerebral embryonic neural tissue grafts to ameliorate the effects of brain damage in marmosets

The transplantation of neuronal tissue into the brains of patients with Parkinson's disease is already being assessed as an experimental treatment for the symptoms of this disease, and the possibility of using similar graft tissue to ameliorate the symptoms of other neurodegenerative diseases is being considered. In this context, a small number of transplant experiments have been carried out in monkeys with lesions of the central dopamine and cholinergic systems. These experiments make it possible to determine the optimum methods of transplantation in an animal whose brain is structurally more closely related to the human than that of the rat and to assess the behavioral consequences of transplantation on symptoms that either resemble very closely the symptoms seen in patients, or are of a complex cognitive nature and are therefore more difficult to measure in the rat. It is intended that these experiments will contribute to the development of better treatments for the neurodegenerative diseases, either by the use of transplantation as a clinical treatment, or by contributing to a better understanding of the mechanisms that normally maintain neuronal function and that fail in these diseases.     

Regulation of surface topography of mouse peritoneal cells. Formation of microvilli and vesiculated pits on omental mesothelial cells by serum and other proteins

The mesothelial cells of the mouse omentum provide an in vivo model for the study of the mobilization of labile microvilli on the cell surface. These mesothelial cells are sparsely covered with microvilli and large pits 150--400 nm in diameter, termed vesiculated pits. On the unstimulated cell, the microvilli average 44/100 microns2 and pits, 30/100 microns 2 of surface and they are rapidly induced to increase in number by the intraperitoneal injection of isologous mouse serum. After 2 min, microvilli increase threefold, continue to sevenfold at 30 min, and decrease to fourfold at 90 min. Vesiculated pits increased with similar kinetics. Bovine serum albumin and gamma globulin also stimulate the microvilli and pits to form, but the response is a slow, gradual rise to five- or sixfold the normal value at 90 min. Evidence indicates that multiple factors, possibly including insulin and immunoglobulins, are involved in the effect of serum. The close physical and temporal relationship between microvilli and pits suggests that a correlation exists in their mobilization by the cell and it is hypothesized that microvilli function in the regulation of the cortical microfilament network in effecting this mobilization.     

Influence of cyclic 3′,5′-adenosine monophosphate on uracil uptake by rifampicin treatedEscherichia coli cells

Summary Incubation of cells from a wild type strain ofE. coli with 0.3 mg/ml rifampicin for 15 minutes lead to a complete inhibition of RNA synthesis measured as the uracil incorporation into the trichloroacetic acid insoluble fraction. In these rifampicin-treated cells [¹⁴C]uracil incorporation tended to decrease during a further incubation at 37°. Addition of cyclic AMP increased the inactivation of the system responsible for [¹⁴C]uracil uptake. The cyclic nucleotide effect seems to be specific since ATP or 5AMP did not increase such inactivation.Dedicated to ProfessorLuis F. Leloir on the occasion of his 70th birthday.     

Studies on reactivated cilia: II. Reactivation of ciliated cortices from the oviduct of anolis cristatellus

Reactivated ciliated cortices from the oviduct of the lizard Anolis cristatellus show symplectic metachrony, and resemble reactivated sea urchin sperm flagella in several characteristics, such as pH optimum and K_mf, but differ in other, such as optimal ionic strength. Cilia isolated from the same source give similar results, but show a poorer reactivation. Purified ciliated cortices have adenylate kinase activity and an ATPase activity with a K_m value identical with the K_mf, suggesting a tight coupling between ATP hydrolysis and movement in this system.