Nucleoside triphosphates are required to open the CFTR chloride channel.

The CFTR Cl- channel contains two predicted nucleotide-binding domains (NBD1 and NBD2); therefore, we examined the effect of ATP on channel activity. Once phosphorylated by cAMP-dependent protein kinase (PKA), channels required cytosolic ATP to open. Activation occurred by a PKA-independent mechanism. ATP gamma S substituted for ATP in PKA phosphorylation, but it did not open the channel. Several hydrolyzable nucleotides (ATP greater than GTP greater than ITP approximately UTP greater than CTP) reversibly activated phosphorylated channels, but nonhydrolyzable analogs and Mg(2+)-free ATP did not. Studies of CFTR mutants indicated that ATP controls channel activity independent of the R domain and suggested that hydrolysis of ATP by NBD1 may be sufficient for channel opening. The finding that nucleoside triphosphates regulate CFTR begins to explain why CF-associated mutations in the NBDs block Cl- channel function.     

On the interpretation of host-parasite ecology: Heligmosomoides polygyrus (Nematoda) in wild wood mouse (Apodemus sylvaticus) populations

This paper describes epidemiological and seasonal patterns in the interaction between wood mice, Apodemus sylvaticus and Heligmosomoides polygyrus. Data used in the analysis were collected by C. S. Elton and co-workers at Bagley Wood, Oxfordshire in the late 1920s. Heligmosomoides polygyrus was by far the most common helminth parasite with 70% of all wood mice infected and average intensity around 12 worms per mouse. Male and female mice were shown to harbour similar parasite burdens. Parasite numbers per host were highly overdispersed and were well described by the negative binomial distribution. There was little evidence for convexity in age (= weight)-intensity curves, either within or across sexes.
Host and parasite numbers showed predictable seasonal patterns, with mouse populations at their largest at the end of the breeding season, in August and September, and parasite populations at their largest in the late spring, around May. Results are discussed in relation to the ecology of H. polygyrus in wood and laboratory mice, and tentative comparison is made with human helminth infection. The interpretation of epidemiological patterns in these data was problematic. Of particular importance was the statistical distribution of parasites within the host population, and possible differences between mouse sexes in relation to growth, survival and trapping. Such difficulties are relevant to a range of similar field data.     

Somatic recombination rather than uniparental disomy suggested as another mechanism by which genetic imprinting may play a role in the etiology of Prader-Willi syndrome

Summary Six Prader-Willi syndrome (PWS) patients with normal karyotypes and their parents were analyzed to determine the nature of the molecular aberrations present in the proximal region of 15q and to determine the parental origin of the aberrant chromosome 15. In addition, the likehood that uniparental disomy plays a significant role in the etiology of PWS patients with normal karyotypes was studied. Restriction fragment length polymorphisms (RFLPs) recognized by seven probes [pML34 (D15S9), pTD3-21, pCGS0.9, pCGS1.1 (D15S10), IR4.3 (D15S11), IR10.1 (DS15S12), p189-1 (D15S13), IR39 (D15S18), and CMW-1 (D15S24)] mapping to the Prader-Willi chromosome region (PWCR) and an additional two probes [pMS1-14 (D15S1); the cDNA of neuromedin B] mapping elsewhere on chromosome 15 were analyzed in the six PWS patients and their parents. Copy number of each locus within the PWCR was determined by densitometry. Molecular rearrangements of the proximal region of 15q were observed in all of the six probands and the origin of the aberrant chromosome 15 when determined was consistently paternal in origin. While data obtained from our six patients does not support the mechanism of disomy, results obtained from three of the six patients show more complex rearrangements hypothesized to have resulted from somatic recombination. These rearrangements have resulted in acquired homozygosity and the lack of a paternal allele at various loci within the PWCR. The presence of only a maternal contribution at certain loci as the result of somatic recombination may be another mechanism by which genetic imprinting plays a role in the presentation of the PWS phenotype.     

A restriction-fragment-length difference detected by the anonymous probe DXS199 exhibits non-Mendelian inheritance.

Anonymous DNA probes were isolated from an X chromosome-enriched flow-sorted library. One of these probes, DXS199, identified a restriction-fragment difference that failed to show Mendelian segregation. All normal females were found to have two AvaII fragments of 6.5 kb and 6.0 kb, whereas all normal males had only the 6.5-kb fragment. DNA from a 49,XXXXY male was found to have both 6.0- and 6.5-kb AvaII fragments, in the same 3:1 ratio as seen in the inactive:active number of X chromosomes. This variant, which reflects a structural difference between active and inactive X chromosomes, is likely to be due to a methylation site on the active X chromosome.     

Population structure,spite, and the iterated Prisoner's Dilemma

Evolutionary stability (sensu Maynard Smith: Evolution and the Theory of Games, Cambridge: Cambridge University Press, 1982) of TIT FOR TAT (TFT) under the social ecology of the iterated Prisoner's Dilemma is a function of the number of pure TFT groups (dyads) in the population, relative to the social position of a focal invading defector. Defecting against TFT always raises the defector's relative intragroup fitness; when Axelrod's (Am. Polit. Sci. Rev. 75:306–318, 1981; The Evolution of Cooperation. New York: Basic Books, 1984) Evolutionary stable strategy (ESS) conditions are met, defection also lowers the absolute fitness of the defector. Here the retaliatory (punishing) character of TFT converts defection into spite, permitting pure TFT groups to sufficiently outproduce the defector for the latter's evolutionary suppression. Increasing the relative impact of spiteful defection on a population lowers the range of evolutionary stability for TFT. When individuals participate in multiple dyads, those participating in the greatest number of dyads are most likely to provide a vehicle for the successful invasion of defection. Within social networks, ESS conditions for TFT are thus individual specific. This logic is generalized to the context of an interated n-person Prisoner's Dilemma, providing a cooperative solution conceptually identical with TFT in the two-person game.     

Negative interactions between Willamette mites and Pacific mites: possible management strategies for grapes

Willamette mites and Pacific mites are often negatively associated on grape vines. In particular, vineyards with early season infestations of the less damaging Willamette mite rarely develop high populations of the economically important Pacific mite. We report that Willamette mites had a negative effect on Pacific mite populations in both the greenhouse and field. In some experiments, the negative effect was more pronounced when vines had been damaged by previous feeding of Willamette mites and in other experiments concurrent feeding by both mite species was necessary to demonstrate a negative effect. Therefore, we cannot conclude if the mechanism of the response involves induced resistance against Pacific mites, more conventional interspecific competition, or both. Since predators were uncommon in our experiments, predator build up on Willamette mites did not cause the low Pacific mite population that we observed, although this mechanism may be important in many vineyards. Further, larger scale experiments are necesary to determine if growers can introduce Willamette mites to help control Pacific mites.

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Résumé E. willametti et T. pacificus sont souvent antagonistes dans les vignobles. En particulier, dans les vignobles contaminés tôt dans la saison par E. willametti,-dont les dégâts sont moins conséquents-, on observe rarement des populations élevées de T. pacificus, dont les dégâts sont économiquement importants. Nous avons constaté que E. Willametti a réduit les populations de T. pacificus, tant en serres qu'à l'extérieur. Dans quelques cas, l'effet antagoniste était plus marqué quand les vignes avaient été préalablement endommagées par l'alimentation de E. willametti. Dans d'autres expériences, la compétition alimentaire entre les deux espèces d'acariens était nécessaire pour produire un effet antagoniste. Cependant, nous ne pouvons pas en conclure que la réponse implique une résistance induite contre T. pacificus, ou une compétition interspécifique plus classique, ou les deux à la fois. Puisque les prédateurs étaient rares dans nos expériences, une explosion des prédateurs sur E. willametti n'a pu provoquer le faible niveau de population observé avec T. pacificus, bien qu'un tel méchanisme puisse être important dans certains vignobles. Quoi qu'il en soit, des expériences à plus grande échelle sont nécessaires pour déterminer si les vignerons peuvent introduire Eotetranychus willametti afin de limiter les populations de Tetranychus pacificus.

     

Effect of subunit III removal on control of cytochrome c oxidase activity by pH

Studies were undertaken to assess the postulated involvement of subunit III in the proton-linked functions of cytochrome c oxidase. The effect of pH on the steady-state kinetic [corrected] parameters of subunit III containing and subunit III depleted cytochrome oxidase was determined by using beef heart and rat liver enzymes reconstituted into phospholipid vesicles. The TNmax and Km values for the III-containing enzyme increase with decreasing pH in a manner quantitatively similar to that reported by Thornstrom et al. [(1984) Chem. Scr. 24, 230-235], giving three apparent pKa values of less than 5.0, 6.2, and 7.8. The maximal activities of the subunit III depleted enzymes (beef heart and rat liver) show a similar dependence on pH, but the Km values are consistently higher than those of the III-containing enzyme, an effect that is accentuated at low pH. The pH dependence of TNmax/Km for both forms of the enzyme (+/- subunit III) indicates that protonation of a group with an apparent pKa of 5.7 lowers the affinity for substrate (cytochrome c) independently of a continued increase in maximal velocity. N,N'-Dicyclohexylcarbodiimide (DCCD) decreases the pH responsiveness of the electron-transfer activity to the same extent in both III-containing and III-depleted enzymes, indicating that this effect is mediated by a peptide other than subunit III. Control of intramolecular electron transfer by a transmembrane pH gradient (or alkaline intravesicular pH) is shown to occur in cytochrome oxidase vesicles with cytochrome c as the electron donor, in agreement with results of Moroney et al. [(1984) Biochemistry 23, 4991-4997] using hexaammineruthenium(II) as the reductant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Factors Affecting High-Oxygen Survival of Heterotrophic Microorganisms from an Antarctic Lake

We sought to determine factors relating to the survival of heterotrophic microorganisms from the high-dissolved-oxygen (HDO) waters of Lake Hoare, Antarctica. This lake contains perpetual HDO about three times that of normal saturation (40 to 50 mg liter⁻¹). Five isolates, one yeast and four bacteria, were selected from Lake Hoare waters by growth with the membrane filter technique with oxygen added to yield dissolved concentrations 14 times that in situ, 175 mg liter⁻¹. One bacterial isolate was obtained from the microbial mat beneath the HDO waters. This organism was isolated at normal atmospheric oxygen saturation. The bacteria were gram-negative rods, motile, oxidase positive, catalase positive, and superoxide dismutase positive; they contained carotenoids. The planktonic isolates grew in media containing 10 mg of Trypticase soy (BBL Microbiology Systems)-peptone (2:1) liter⁻¹ but not at 10 g liter⁻¹. Under low-nutrient levels simulating Lake Hoare waters (10 mg liter⁻¹), two of the planktonic isolates tested were not inhibited by HDO. Growth inhibition by HDO increased as nutrient concentration was increased. A carotenoid-negative mutant of one isolate demonstrated a decreased growth rate, maximal cell density, and increased cell lysis in the death phase under HDO compared with the parent strain. The specific activity of superoxide dismutase was increased by HDO in four of the five bacterial isolates. The superoxide dismutase was of the manganese type on the basis of inhibition and electrophoretic studies. The bacterial isolates from Lake Hoare possess several adaptations which may aid their survival in the HDO waters, as well as protection due to the oligotrophic nature of the lake.     

A similar ribosomal protein S6 kinase activity is found in insulin-treated 3T3-L1 cells and chick embryo fibroblasts transformed by Rous sarcoma virus

Insulin and transformation by Rous sarcoma virus stimulate the phosphorylation of ribosomal protein S6. Soluble fractions containing activated S6 protein kinase from insulin-treated cells and from transformed chick embryo fibroblasts were compared. Based upon several characteristics notably elution from DEAE-cellulose and sedimentation in glycerol gradients, these two S6 protein kinase activities appear to be similar enzymes. Thus insulin and retroviral transformation may activate the same enzyme to regulate the phosphorylation state of S6.