The metabolism of deoxyguanosine in mitochondria. Characterization of the uptake process

Summary The uptake of deoxyguanosine by rat liver mitochondria was characterized. The process required an intact mitochondrial membrane and exhibited a dependence on added phosphate. Deoxyguanosine uptake was minimally influenced by Mg²⁺ or Mn²⁺, but Ca²⁺ at concentrations above 0.5 mM were detrimental. Of the deoxynucleosides tested, only deoxyinosine inhibited the uptake of deoxyguanosine. The ribonucleoside guanosine was not observed to compete with its deoxynucleoside analog. Known inhibitors of nucleoside transport, cytochalasin B and NBMPR, did not block deoxyguanosine uptake, but the sulfhydryl reagents NEM and pCMB were both inhibitory. The uptake of deoxyguanosine was shown to be a saturable process and an apparent Km of 0.64 M was calculated from a Hanes plot.     

Depressed natural cytotoxicity but normal natural killer cytotoxic factor (NKCF) production by mononuclear cells derived from patients with hepatocellular carcinoma

Summary This study investigated the relation between the production of natural killer cytotoxic factors (NKCF) and the phenomenon of natural killing (NK) activity against target K562 cells. Two different models of defective NK cell activity were employed. In the first instance, cytotoxic activity of mononuclear cells (MN) derived from patients with hepatocellular carcinoma was compared to the ability of these cells to produce NKCF. Although direct cytotoxicity was considerably impaired in these patients, the ability of their MN to produce NKCF when stimulated with K562 cells was found to be normal. In the second model, MN treated with the lysosomotropic drug monensin showed considerably reduced direct cytotoxic activity, although they were capable of producing normal amounts of NKCF when activated by K562 cells. These results therefore indicate that there is no correlation between NK activity and corresponding NKCF release, and suggest that NKCF production and activity is independent of direct NK cytotoxic activity.     

p82H identifies sequences at every human centromere

Summary A cloned alphoid sequence, p82H, hybridizes in situ to the centromere of every human chromosome. After washing under stringent conditions, no more than 8% of the grains are located on any specific chromosome. p82H thus differs from other centromeric sequences which are reported to be chromosome specific, because it detects sequences that are conserved among the chromosomes. Two experimental approaches show that the p82H sequences are closely associated with the centromere. First, p82H remains with the relocated centromeres in an inv(19) and an inv(6) chromosome. Second, p82H hybridizes at the centromere but not to the centromeric heterochromatin of chromosomes 1, 9 and 16 that have elongated 1qh, 9qh and 16qh regions produced by short growth in 5-azacytidine. The only noncentromeric site of hybridization is at the distal end of the 9qh region.     

Plant feeding of yellow baboons (Papio cynocephalus) in Mikumi national park,Tanzania, and the relationship between seasonal feeding and immature survival

Focal-animal feeding data obtained from 64 adult baboons during a 3-year period were used together with equivalent data from 46 infants to evaluate hypotheses predicting selection for a birth peak and to study the baboon’s eclectic/selective feeding adaptation, with emphasis on differential feeding by sex, developmental trends, and seasonal use of food classes (fruit, leaf, flower, grass, etc.). The findings suggest that feeding conditions are better in the wet season than in the dry season. Despite large sexual dimorphism, estimates of total amounts eaten were virtually identical for males and females. Infants used all of the same plant-food classes as adults, but proportional differences occurred for some food classes in amounts eaten. Foods eaten proportionately less by infants were probably harder for them to obtain and process or were chosen through inexperience or for exploration. There was considerable between-year variation in amounts of food classes eaten, but the within-year standard deviations were similar, as were also the mean amounts eaten per year. An eclectic/selective feeding adaptation has the advantage of permitting long-run acquisition of adequate nutrition within a context of high feeding variation from season to season and year to year. Mixed results were obtained from hypotheses about selection for a birth peak. Although a peak occurred in the early dry season, this was not the optimal time of birth for survival. Survival was highest for individuals born in the late wet season, when the availability and probably the quality of food for lactating mothers were greatest.     

Obligation and the new naturalism

Although it has become increasingly evident that an adequate theory of obligation must rest on evolutionary biology and human ethology, attempts toward this end need to explore the full range of personal, cultural, and political obligations observed in our species. The new naturalism reveals the complexity of social behavior and the defects of reductionist models that oversimplify the foundations of human duties and rights. Ultimately, this approach suggest a return to the Aristotelian concept of natural justice.     

Purinergic modulation of cardiac activity in the flounder during hypoxic stress

Summary The interaction of adrenaline and adenosine was examined in cardiac tissue of the flounderPlatichthys flesus.When applied alone both agents increased contractility in both auricular and ventricular myocardial strips. This positive inotropic effect was associated with a small depolarization in the tissues examined by the sucrose gap technique. Simultaneous application of adrenaline and adenosine gave an inhibition of the control responses seen with either agent alone in both auricle and ventricle.Radiocalcium flux studies on ventricular tissue showed that influx was increased by adrenaline or adenosine alone above control values, but when applied together radiocalcium influx was reduced. Radiocalcium efflux from cardiac microsomes was stimulated by challenge with adrenaline or adenosine alone. This stimulation was not seen following simultaneous challenge by both agents.The effect of adrenaline on responses of hypoxic flounder hearts was less than that seen in normoxic hearts. This situation was reversed by pretreatment with the purine receptor blocker caffeine. Caffeine pretreatment also reduced the positive inotropic effect seen in normoxic hearts challenged with adenosine.TLC studies gave strong evidence that hearts perfused with hypoxic salines produced both adenosine and adrenaline.The results are discussed as evidence for a mechanism of heart regulation which the flounder may use as a defence against severe acute hypoxic stress.     

Expression of a mouse metallothionein-Escherichia coli β-galactosidase fusion gene (MT-βgal) in early mouse embryos

We have microinjected DNA containing the inducible mouse metallothionein-I (MT-I) promoter, coupled to the structural gene for Escherichia coli β-galactosidase (lacZ), into the pronuclei of one-cell mouse embryos. A qualitative histochemical assay, with 5-bromo-4-chloro-3-indolylβ- -galactopyranoside (X-Gal) as a substrate, was used to detect expression of lacZ at several preimplantation stages. We observed staining indicative of exogenous β-galactosidase activity in 5–17% of DNA-injected embryos assayed at preimplantation stages after 16–24 h treatment with ZnSO₄. Thus, lacZ can be used as an indicator gene for promoter function during early mouse embryogenesis, and the incorporation of the MT-I promoter into fusion genes can be a useful means of controlling the expression of exogenous genes in preimplantation mouse embryos.