Definition of a consensus binding site for p53.

Recent experiments have suggested that p53 action may be mediated through its interaction with DNA. We have now identified 18 human genomic clones that bind to p53 in vitro. Precise mapping of the binding sequences within these clones revealed a consensus binding site with a striking internal symmetry, consisting of two copies of the 10 base pair motif 5'-PuPuPuC(A/T)(T/A)GPyPyPy-3' separated by 0-13 base pairs. One copy of the motif was insufficient for binding, and subtle alterations of the motif, even when present in multiple copies, resulted in loss of affinity for p53. Mutants of p53, representing each of the four "hot spots" frequently altered in human cancers, failed to bind to the consensus dimer. These results define the DNA sequence elements with which p53 interacts in vitro and which may be important for p53 action in vivo.     

Heterogeneous responses of canine basilar and middle cerebral arteries to serotonin at normal and high CO2 tension

The responses of basilar arteries (BAs) to serotonin were attenuated by high \(P_{CO_2 } \) (86±1 mm Hg) and the pH matched acidotic solution ( \(P_{CO_2 } \) 37±1 mm Hg), whereas the responses of middle cerebral arteries (MCAs) were not. High \(P_{CO_2 } \) decreased the basal tone of both arteries, and the changes in basal tone due to high \(P_{CO_2 } \) were not influenced by 3×10^?7 M imipramine, 10^?5 M pargyline or 10^?4 M aspirin. The responses of BAs to serotonin were attenuated by high \(P_{CO_2 } \) in the presence of imipramine, pargyline and aspirin. The responses of MCAs to serotonin were not influenced by high \(P_{CO_2 } \) in the presence of pargyline and aspirin, but attenuated by high \(P_{CO_2 } \) in the presence of imipramine.     

The life span of the biosphere revisited

A decade ago, Lovelock and Whitfield raised the question of how much longer the biosphere can survive on Earth. They pointed out that, despite the current fossil-fuel induced increase in the atmospheric CO2 concentration, the long-term trend should be in the opposite direction: as increased solar luminosity warms the Earth, silicate rocks should weather more readily, causing atmospheric CO2 to decrease. In their model, atmospheric CO2 falls below the critical level for C3 photosynthesis, 150 parts per million (p.p.m.), in only 100 Myr, and this is assumed to mark the demise of the biosphere as a whole. Here, we re-examine this problem using a more elaborate model that includes a more accurate treatment of the greenhouse effect of CO2, a biologically mediated weathering parameterization, and the realization that C4 photosynthesis can persist to much lower concentrations of atmospheric CO2(<10 p.p.m.). We find that a C4-plant-based biosphere could survive for at least another 0.9 Gyr to 1.5 Gyr after the present time, depending respectively on whether CO2 or temperature is the limiting factor. Within an additional 1 Gyr, Earth may lose its water to space, thereby following the path of its sister planet, Venus.     

C1 inhibitor hinge region mutations produce dysfunction by different mechanisms.

Heterozygosity for a mutant dysfunctional C1 inhibitor protein, a member of the serine proteinase inhibitor (serpin) superfamily, results in type II hereditary angioneurotic oedema. We identified a "hinge" region mutation in C1 inhibitor with a Val to Glu replacement at P14 Val-432. Recombinant C1 inhibitors P10 Ala-->Thr and P14Val-->Glu did not form stable complexes with fluid phase C1s or kallikrein. The P14 Val-->Glu mutant, however, was cleaved to a 96K form by C1s, while the P10 Ala-->Thr mutant was not. The recombinant P10 mutant also did not complex with C1s, kallikrein or beta-factor Xlla-Sepharose. The two mutations, therefore, result in dysfunction by different mechanisms: in one (P14 Val-->Glu), the inhibitor is converted to a substrate, while in the other (P10 Ala-->Thr), interaction with target protease is blocked.     

A frameshift mutation in the gamma E-crystallin gene of the Elo mouse.

The murine Elo (eye lens obsolescence) mutation confers a dominant phenotype characterized by malformation of the eye lens. The mutation maps to chromosome 1, in close proximity to the gamma E-crystallin gene which is the 3'-most member of the gamma-crystallin gene cluster. We have analysed the sequence of this gene from the Elo mouse and identified a single nucleotide deletion which destroys the fourth and last "Greek key" motif of the protein. This mutation is tightly associated with the phenotype, as no recombination was detected in 274 meioses. In addition, the mutant mRNA is present in the affected lens, providing further support for our hypothesis that the deletion is responsible for the dominant Elo phenotype.     

Flow-induced release of adenosine 5′-triphosphate from endothelial cells of the rat mesenteric arterial bed

Adenosine 5-triphosphate (ATP) was released into the perfusate of rat isolated mesenteric arterial beds during each of two consecutive increases in flow. There was no significant difference between the amounts of ATP released on each occasion. Substance P was also released into the perfusate by increased flow, although its release was more variable. Removal of the endothelium of the mesenteric vessels with sodium deoxycholate led to a significant reduction (74%) in the amount of ATP released compared with the release before the endothelium had been removed. This suggests that the ATP released into the mesenteric arterial perfusate during increased flow arises from endothelial cells.     

Immunogenetics

Summary The 1985 Catalog of Mapped Genes (Human Gene Mapping 8; 33) has been used to pick out the known, immunologically important genes; these are then discussed in the following order: 1. genes controlling organs, tissues and cells of the immune apparatus, 2. genes determining self structures, 3. genes determining the structures of immunological specificity, 4. genes determining substances with immunoregulatory and effector properties. The symbols for the genes and the biological functions of their products are explained. The genetics of the ABO blood groups, of the HLA-system and of antibody formation are given in rather more detail.     

Determination of erythrocyte pyrimidine 5′-nucleotidase activity by31P nuclear magnetic resonance: Comparison of normal controls and multiple sclerosis patients

Summary A technique to assay erythrocyte pyrimidine 5-nucleotidase activity in situ using³¹P nuclear magnetic resonance spectroscopy is presented. The assay is chemically specific, simple and applicable to untreated lysates. A comparison of enzyme levels in normal controls and in multiple sclerosis patients employing the assay yielded no significant differences between both groups. Difficulties encountered in the quantitative analysis of the assay using¹H-NMR spectroscopy are briefly discussed.     

Molt-induced muscle atrophy decreases the zinc content of the pectoralis of the Giant Canada Goose (Branta canadensis maxima)

Summary During molt-induced atrophy of the pectoralis muscle of the Giant Canada Goose (Branta canadensis maxima), the zinc content of the muscle was significantly reduced (p0.0139), though the concentration of zinc per unit weight of muscle appeared higher (p0.0232). Zinc lost from the muscle during molt could be utilized for growth of the new flight feathers.Acknowledgments. Funds for this study were obtained from an operating grant awarded to J. C. G. by the Natural Sciences and Engineering Research Council of Canada.