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  • 1995-1999  (59)
  • 1
    ISSN: 1432-1793
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A key regulatory mechanism underlying the switch between aerobic and anaerobic metabolism amongst anoxia-tolerant marine molluscs is reversible protein phosphorylation. To assess the role of cAMP-dependent protein kinase (PKA) in aerobic–anaerobic transitions, the effects of anoxia on the activity and subcellular distribution of PKA were assessed in foot and hepatopancreas of the marine periwinkle, Littorina littorea. Exposure to N2 gas at 5 °C caused a rapid decline in the percentage of total enzyme present as the free catalytic subunit (PKAc) in both tissues; the percentage of PKAc fell from ∼30% in controls to 3% after 1 h anoxia and remained low over 72 h. Total PKA also fell by 30% after 72 h anoxia in hepatopancreas but rebounded during aerobic recovery. Freezing at −8 °C elicited parallel results for both percentage of PKAc and total PKA, suggesting that PKA responses to freezing were stimulated by the ischemia that develops when hemolymph freezes. Anoxia also led to a shift in PKA subcellular distribution in hepatopancreas (but not in foot), the percentage of total PKA activity associated with the nuclear fraction dropping from 25% in controls to 8% in 12 h anoxic snails with opposite changes in the cytosolic fraction. The catalytic subunit (PKAc) of foot PKA was purified to a final specific activity of 63.5 nmol phosphate transferred per minute per milligram protein. Enzyme properties included a molecular weight of 33 to 35 kDa, an activation energy from Arrhenius plots of 65.1 ± 4.8 kJ mol−1, and substrate affinity constants of 151 ± 6 μM for the phosphate acceptor, Kemptide, and 72 ± 9 μM for Mg.ATP. Activity was strongly reduced by mammalian PKA inhibitors (H-89, PKA-I), by neutral chloride salts (I50 values 165 to 210 mM) and by NaF (I50 62 mM). Reduced PKA activity under anoxic or freezing conditions would facilitate the observed suppression of the activities of numerous enzymes that are typically PKA-activated and thereby contribute to the overall anoxia-induced metabolic rate depression.
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  • 2
    ISSN: 1432-1041
    Keywords: Diflunisal ; Probenecid ; steady state pharmacokinetics ; glucuronidation ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of probenecid on the pharmacokinetics of diflunisal and its glucuronide and sulphate conjugates was studied in 8 healthy volunteers. Diflunisal 250 mg b. d. was administered p. o. for 15 days and its steady state pharmacokinetics was evaluated on Day 16 after the last dose (control phase). Probenecid 500 mg b. d. was co-administered throughout the entire study period in the treatment phase of the study. The steady state plasma concentration of diflunisal was significantly higher during the probenecid treatment phase as compared to the control phase (104.0 vs. 63.1 μg·ml−1). This was the result of a significant decrease in the plasma clearance of diflunisal from 5.8 (control) to 3.4 ml·min−1 (probenecid co-administration). The metabolite formation clearances of both glucuronides were significantly decreased by probenecid, -45 % and -54 % for the phenolic and acyl glucuronide, respectively. The metabolite formation clearance of the sulphate conjugate was not affected by probenecid co-administration. Steady state plasma concentrations of the sulphate and glucuronide conjugates of diflunisal were 2.5- to 3.1-fold higher during probenecid co-administration, due to a significant reduction in the renal clearance of the three diflunisal conjugates. Probenecid also reduced the plasma protein binding of diflunisal, but only to a minor extent; the unbound plasma fraction of diflunisal at steady state averaged between 5 and 30 % higher during probenecid co-administration.
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  • 3
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 102 (1995), S. 6241-6250 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: Three weighted, complex nonlinear least-squares methods for the deconvolution of dielectric or conducting system frequency-response data are described and applied to synthetic data and to dielectric data of n-pentanol alcohol, water, and glycerol. The first method represents a distribution of relaxation times or transition rates by an inherently discrete function. Its inversion accuracy and resolution power are shown to be limited only by the accuracy of the data when the data themselves arise from a discrete distribution involving an arbitrary number of spectral lines. It is shown that those inversion methods employed here which allow the relaxation times to be free variables are much superior to those where these quantities are fixed. Furthermore, free-τ methods allow unambiguous discrimination between discrete and continuous distributions, even for data with substantial errors. Contrary to previous conclusions, discrete distributions were determined for both n-pentanol alcohol and water. A complex, continuous distribution estimate was obtained for glycerol. Algorithms for all approaches are incorporated in a readily available computer program. Serious problems with some previous dielectric inversion methods are identified. Finally, several possibilities are mentioned that may allow greater inversion resolution to be obtained for complex nonlinear least-squares estimation of continuous distributions from noisy data. © 1995 American Institute of Physics.
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  • 4
    ISSN: 1365-2486
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering , Geography
    Notes: The exchange of CH4 between tropical forests and the atmosphere was determined by simultaneously measuring the net CH4 flux at the soil surface and assessing the flux contribution from soil-feeding termite biomass, both within the soil profile and in mounds. In Cameroon the flux of CH4 ranged from a net emission of 40.7 ng m–2 s–1 to a net CH4 oxidation of –53.0 ng m–2 s–1. Soil-inhabiting termite biomass was significantly correlated with CH4 flux. Termite mounds emitted up to 2000 ng s–1 mound–1. Termite-derived CH4 emission reduced the soil sink strength by up to 28%. Disturbance also had a strong effect on the soil sink strength, with the average rate of CH4 oxidation, at – 17.5 ng m–2 s–1, being significantly smaller (≈ 36%) at the secondary forest site than the –27.2 ng m–2 s–1, observed at the primary forest site. CH4 budgets calculated for each site indicated that both forests were net sinks for CH4 at – 6.1 kg ha–1 y–1 in the near-primary forest and – 3.1 kg ha–1 y–1 in the secondary forest.In Borneo, three forest sites representing a disturbance gradient were examined. CH4 oxidation rates ranged from 0 to – 32.1 ng m–2s–1 and a significant correlation between the net flux and termite biomass was observed only in an undisturbed primary forest, although the biomass was insufficient to cause net emission of CH4. Rates of CH4 oxidation were not significantly different across the disturbance gradient but were, however, larger in the primary forest (averaging – 15.4 ng m–2 s–1) than in an old-growth secondary forest (–13.9 ng m–2s–1) and a young secondary re-growth (– 10.8 ng m–2s–1). CH4 flux from termite mounds ranged from net oxidation in an abandoned mound to a maximum emission of 468 ng s–1 mound–1. CH4 budgets calculated for each site indicated that CH4 flux from termite mounds had an insignificant effect on the budget of CH4 at the regional scale at all three forest sites. Annual oxidation rates were – 4.8, – 4.2 and – 3.4 kg ha–1 y–1 in the primary, secondary and young secondary forests, respectively.
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  • 5
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 84 (1998), S. 812-827 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The ionic conductivity of glassy, fast-ion-conducting materials can show non-Arrhenius behavior and approach saturation at sufficiently high temperatures [J. Kincs and S. W. Martin, Phys. Rev. Lett. 76, 20 (1996)]. The Ngai coupling model was soon applied to explain some of these observations [K. L. Ngai and A. K. Rizos, Phys. Rev. Lett. 76, 1296 (1996)], but detailed examination and generalization of the coupling model suggested the consideration of a related, yet different, approach, the cutoff model. Although both the coupling and cutoff models involve a shortest nonzero response time, τc, and lead to single-relaxation-time Debye response at limiting short times and high frequencies, they involve different physical interpretations of their low- and high-frequency response functions. These differences are discussed; the predictions of both models in the frequency and time domains are compared; and the utility of both models is evaluated for explaining the non-Arrhenius conductivity behavior associated with the dispersed frequency response of zAgI+(1−z)[0.525Ag2S+0.475B2S3:SiS2] glass for z=0 and 0.4. The cutoff approach, using simulation rather than direct data fitting, yielded semiquantitative agreement with the data, but similar analysis using the coupling model led to poor results. The coupling model leads to an appreciable slope discontinuity at the τc transition point between its two separate response parts, while the cutoff model shows no such discontinuity because it involves only a single response equation with a smooth transition at τc to limiting single-relaxation-time response. The greater simplicity, utility, and generality of the cutoff model suggest that it should be the favored choice for analyzing high-conductivity data exhibiting non-Arrhenius behavior. © 1998 American Institute of Physics.
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  • 6
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 82 (1997), S. 3962-3971 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Given a fitting model, such as the Kohlrausch–Williams–Watts (KWW)/stretched-exponential response, three plausible approaches to fitting small-signal frequency or time-response data are described and compared. Fitting can be carried out with either of two conductive-system formalisms or with a dielectric-system one. Methods are discussed and illustrated for deciding which of the three approaches is most pertinent for a given data set. Limiting low- and high-frequency log–log slopes for each of the four immittance levels are presented for several common models; cutoff effects are considered; and an anomaly in the approach to a single-relaxation-time Debye response for one of the conductive-system approaches is identified and explained. It is found that the temporal response function for the most appropriate conductive-system dispersion (CSD) approach, designated the CSD1, one long used in approximate form for frequency-response data analysis, does not lead to stretched-exponential transient behavior when a KWW response model is considered. Frequency-domain fitting methods and approaches are illustrated and discriminated using 321 and 380 K Na2O–3SiO2 data sets. The CSD1 approach using a KWW model is found to be most appropriate for fitting these data exceedingly closely with a complex nonlinear least-squares procedure available in the free computer program LEVM. Detailed examination and simulation of the approximate, long-used CSD1 modulus fitting formalism shows the unfortunate results of its failure to include separately the effects of the always present high-frequency-limiting dielectric constant, εD∞. The stretched-exponential exponent, β, associated with this fitting approach has always been misidentified in the past, and even after its reinterpretation, the result is likely to be sufficiently approximate that most physical conclusions derived from such fitting will need reevaluation. © 1997 American Institute of Physics.
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  • 7
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 82 (1997), S. 1476-1478 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The conclusion [K. L. Ngai, A. K. Rajagopal, R. W. Rendell, and S. Teitler, Phys. Rev. B 28, 6073 (1983)] that simple exponential decay is a nonviable model for electrical relaxation, because it fails to satisfy the fundamental Paley–Wiener Fourier transform criterion, is shown by direct analysis to be inapplicable to small-signal electrical relaxation situations. Thus, not only is exponential decay and its associated single-relaxation-time Debye frequency response a valid model for relaxation, but, by extension, all distributions of relaxations times and energies which use a superposition of simple exponentials or Debye functions are also acceptable descriptions of relaxation phenomena. Reasons why the earlier conclusion is nonviable in the present context are discussed. © 1997 American Institute of Physics.
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  • 8
    ISSN: 1072-8368
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] A family of potent insecticidal toxins has recently been isolated from the venom of Australian funnel web spiders. Among these is the 37-residue peptide ω-atracotoxin-HV1 (ω-ACTX-HV1) from Hadronyche versuta. We have chemically synthesized and folded ω-ACTX-HV1, shown that it is ...
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Perspectives in drug discovery and design 15-16 (1999), S. 61-69 
    ISSN: 1573-9023
    Keywords: hanatoxins ; heteropodatoxins ; funnel-web spider toxins ; spider toxins ; voltage-gated K+ channels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Spider toxins that target potassium channels constitute a new class of pharmacological tools that can be used to probe the structure and function of these channels at the molecular level. The limited studies performed to date indicate that these peptide toxins may facilitate the analysis of K+ channels that have proved insensitive to peptide inhibitors isolated from other animal sources. Thus far, two classes of K+ channel-selective spider toxins have been isolated, sequenced, and pharmacologically characterised – the hanatoxins (HaTx) from Grammastola spatulata and heteropodatoxins (HpTx) from Heteropoda venatoria. The hanatoxins block Kv2.1 and Kv4.2 voltage-gated K+ channels. In Kv2.1 K+ channels this occurs as a consequence of a depolarising shift in the voltage dependence of activation and not by occlusion of the channel pore. These toxins show minimal sequence homology with other peptide inhibitors of K+ channels, but they do share some homology with other ion channel toxins from spiders, particularly with regard to the spacing between cysteine residues. We have recently isolated three K+ channel antagonists from the venom of the Australian funnel-web spider Hadronyche versuta; at least two of these toxins are likely to constitute a new class of spider toxins active on K+ channels as they are approximately twice as large as HaTx and HpTx.
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  • 10
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Modification of synaptic strength in the mammalian central nervous system (CNS) occurs at both pre- and postsynaptic sites,. However, because postsynaptic receptors are likely to be saturated by released transmitter, an increase in the number of active postsynaptic receptors may be a more ...
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