dUTP pyrophosphatase (dUTPase; EC 3.6.1.23) catalyses the hydrolysis of dUTP to dUMP and PPi and thereby prevents the incorporation of uracil into DNA during replication. Although it is widely believed that dUTPase is essential for cell viability because of this role, direct evidence supporting this assumption has not been presented for any eukaryotic system. We have analysed the role of dUTPase (DUT1) in the life cycle of yeast. Using gene disruption and tetrad analysis, we find that DUT1 is necessary for the viability of S. cerevisiae; however, under certain conditions dut1 null mutants survive if supplied with exogenous thymidylate (dTMP). Analyses with isogenic uracil‐DNA‐glycosylase (UNG1) deficient or proficient strains indicate that in the absence of dUTPase, cell death results from the incorporation of uracil into DNA and the attempted repair of this damage by UNG1‐mediated excision repair. However, in dut1 ung1 double mutants, starvation for dTMP causes dividing cells to arrest and die in all phases of the cell cycle. This latter effect suggests that the extensive stable substitution of uracil for thymine in DNA leads to a general failure in macromolecular synthesis. These results are in general agreement with previous models in thymine‐less death that implicate dUTP metabolism. They also suggest an alternative approach for chemotherapeutic drug design.
Two theories are applied to measurements of the decrease in apparent viscosity of blood in narrow tubes (Fahraeus-Lindqvist effect). First, the effect may be attributed to the presence of unsheared laminae in the fluid (sigma phenomenon), and it was found that the thickness of such laminae must vary between 3.5 µ at 10% hematocrit and 34 µ at 80%. Alternatively, the effect may be caused by a cell-free marginal zone adjacent to the tube wall, which would have to be 6 µ thick at 10% hematocrit and 1.5 µ at 80%. There is a slight suggestion in the data that the effect may be reversed as the flow rate approaches zero (i.e. the apparent viscosity rises in small tubes). Finally, a method is proposed for calculating the effective diameter of a vascular bed, and it was found to be 55 µ for a dog's hind limb.
The role of the non-Newtonian behavior of blood in perfused vascular beds has been assessed by measuring the pressure-flow curves of erythrocyte suspensions with hematocrits from 9 to 85%, in glass tubes of radii from 50 to 800 µ. The curves become linear as the flow increases, and for each tube, point back to a ‘nodal point’ on the negative flow axis which is independent of hematocrit. From this data, curves of the rate of shear versus shearing stress at the wall (consistency curves) were obtained which are all linear at stresses greater than 20 dynes/cm. The wall shearing stress in all categories of blood vessels is greater than this, especially in the arterioles where it is 200 dynes/cm. It is concluded that in perfused vascular beds the flow properties of blood are essentially linear in the physiological working range so that the distensibility of the vessels is the all important factor in determining the shape of the pressure-flow curves.
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