Allosteric proteins after thirty years: The binding and state functions of the neuronalα7 nicotinic acetylcholine receptors

A key statement of the 1965 Monod-Wyman-Changeux (MWC) model for allosteric proteins concerns the distinction between the ligand-binding function ( ) and the relevant state function ( ). Sequential models predict overlapping behavior of the two functions. In contrast, a straightforward experimental consequence of the MWC model is that for an oligomeric protein the parameters which characterize the two functions should differ significantly. Two situations, where \bar Y$$ " align="middle" border="0"> and the system ishyper-responsive or where and the system ishypo-responsive, have been encountered. Indeed, the hyper-responsive pattern was first observed for the enzyme aspartate transcarbamoylase, by comparing with monitored by a change in sedimentation. Extensions of the theory to ligand-gated channels led to the suggestion that, on the one hand, hyper-responsive properties also occur with high-affinity mutants. On the other hand, native channels of the acetylcholine neuronal7 receptor and low-affinity mutants of the glycine receptor can be interpreted in terms of the hypo-responsive pattern. For the ligand-gated channels, whereas is detected directly by ion flux, ligand binding has rarely been measured and the formation of desensitized states may complicate the analysis. However, stochastic models incorporating both binding and channel opening for single molecules predict differences that should be measurable with new experimental approaches, particularly fluorescence correlation spectroscopy.     

Proton-induced dismutation of superoxide in aprotic media by bile pigments

Summary Cyclic voltammetry of molecular oxygen in aprotic media (dimethylformamide) and in the presence of bilirubin and other bile pigments shows that superoxide anion ( ) undergoes proton-induced dismutation. Lactam hydrogens of bile pigments are sufficiently acid to induce disproportionation to O₂ and H₂O₂. Because of its characteristic lipophilic behavior, a biological role for natural bilirubin similar to that of other non-enzymatic lipophilic scavengers of is suggested.     

Effects of DL-propranolol on exercise heart rate and maximal rates of oxygen consumption inScaphiopus intermontanus

Summary Lymphatic injection of propranolol (0.2–10 g) into toads decreased exercise heart rate in a dose-dependent manner. There was a significant linear corrleation between exercise heart rate and maximal oxygen consumption rates . These data are consistent with the hypothesis that blood oxygen transport is the limiting process for max in anuran amphibians.This work was supported by a grant from the National Science Foundation (PCM-8021808). I am grateful to Dr P.C. Withers for logistical support and Dr S. Yokota for the initial idea.     

Superoxide anion scavenging effect and superoxide dismutase activity ofGinkgo biloba extract

Summary Ginkgo biloba extract is known to be efficient in diseases associated with free radical generation. The purpose of this work was to study, under in vitro conditions, the action ofGinkgo biloba extract (Gbe) against superoxide anion ( ), which is directly or indirectly implicated in cell damage.Gbe appears to have both an scavenging effect and also a superoxide dismutase activity. Its antiradical effect was demonstrated by low temperature electron spin resonance and in a non-enzymatic system (phenazine methosulfate-NADH), and its enzymatic activity was shown by polarographic determination.     

Diurnal variations in thermoregulatory responses to intrahypothalamic and intravenous injections of noradrenaline in the pigeon

Summary The differences in responses of T_b, T_f and both to intrahypothalamic and i.v. administration of NA were measured both at noon and at midnight in the pigeon. Although the T_b and were at a higher level in the daytime, no differences in the magnitude of the fall in and T_b were obtained after either intrahypothalamic or i.v. injections of NA, whether it was measured during the day or at night. The only marked difference was the more prominent vasodilatation in the daytime after both routes of injection.     

Scaling of respiratory areas in relation to oxygen consumption of vertebrates

Summary Resting oxygen consumption is generally related to the 0.75 power of the body mass. More recent studies on the morphometry of the lungs and gills of vertebrates indicate that the respiratory surfaces increase in area more closely to M^1.0. A possible explanation is that the gas exchange surface is more to be related to themaximum oxygen uptake capacity, rather than to the resting condition. However, recent studies, especially in African mammals, suggest that scales to a power similar to that for resting oxygen consumption and hence cannot be directly related to the respiratory surfaces.In fishes the situation seems to be different as appears to increase more rapidly than standard . Consequently, the ratio between these two is greater in larger specimens and hence they have a greater scope for activity. A possible interpretation of this apparent difference may be related to differences in ventilation, as the tidal ventilation of lungs can lead to a reduction in the difference in oxygen pressure across the exchange surface, whereas in fish gills with increasing size and increasing water velocity there would be a reduction in the resistance to gas transfer. However, it is important to appreciate that such generalizations probably do not hold in all cases and the position of intermediate groups of vertebrates needs to be more closely assessed.This paper is based upon part of a lecture given at the Conference of Comparative Respiratory Physiology, Göttingen, BRD, August 1982.     

Reaction time of the topminnowAplocheilus lineatus to surface waves determined by video- and electromyogram recordings

Summary Evoked muscle potentials during a localizing response for a wave center occur inAplocheilus lineatus 30±1.5 msec ( ) earlier than the simultaneously monitored body movements. Considering this time, only the first 8–10 wave cycles of a total wave signal are utilized to identify and localize a wave source.This study was supported by the Deutsche Forschungsgemeinschaft.     

Identification of calcium antagonist receptor binding sites using (3H)nitrendipine in bovine tracheal smooth muscle membranes

Summary (³H)Nitrendipine binding to the bovine tracheal muscle membrane at 25°C was rapid, saturable (B_max=14.8±3.9fmol/mg protein) and of high affinity (K_d=0.15±0.04 nM). The rank order of Ca²⁺ antagonists competing for airway (³H)nitrendipine binding was nitrendipine nisoldipine nifedipine » verapamil. Cromolyn, however, neither inhibited nor increased the binding.J.B.C. is a visiting associate professor at the NYMMC. We thank Ms. Pang-jang Chang for technical assistance. This work is supported by a grant (NSC 72-0412-BO10-R20) from the National Science Council, ROC. To whom reprint requests should be addressed: Allergic Disease Center, Creighton University School of Medicine, Omaha, Nebraska 68178.     

Bildung von Reaktionsholz durch Zentrifugalbeschleunigung

Summary In leaning stems, reaction wood can be formed as a response to gravitation stimulus. In seedlings ofAesculus hippocastanum, reaction wood formation could likewise be stimulated by centrifugation. This proved the differentiation of wood cells to be affected by mass acceleration. The reaction wood formation is related quantitatively to mass accelerationb and timet, the formation of reaction wood being described by quantitative stimuli law as . The threshold of stimulation lies in the dimension . The arrangement of the experiments permits a direct approach to cambium physiology and the following differentiation of wood cells.     

Ginkgo biloba extract inhibits oxygen species production generated by phorbol myristate acetate stimulated human leukocytes

Summary A Ginkgo biloba extract (Gbe) containing flavonoids, among other compounds, was tested for the release of activated oxygen species ( , H₂O₂, OH^.) during the stimulation of human neutrophils (PMNs) by a soluble agonist. The extract slows down O₂-consumption (respiratory burst) of stimulated cells by its inhibitory action on NADPH-oxidase, the enzyme responsible for the reduction of O₂ to . Consequently, superoxide anion ( ) and hydrogen peroxide (H₂O₂) production is significantly decreased when the PMNs stimulation is done in the presence of the extract at concentrations of 500, 250 and 125 g/ml. Moreover, the hydroxyl radical generation (OH^.) is very much decreased at concentrations as low as 15.6 g Gbe/ml, which indicates that the extract also has free radical scavenging activity. Gbe is able at least to reduce very severel the activity of myeloperoxidase contained in neutrophils. This enzyme, secreted into the intra and extracellular medium, catalyzes the oxidation of chloride (Cl^–) by H₂O₂ to yield strong oxidants (HOCl, chloramines) which are implicated in inflammatory processes     

Improved response to heat after moderate physical training in man

Summary 7 young men marched for 6 days (35 km daily) in a cool climate at about 35% of their . Sweat output was measured at rest in a climatic chamber during a controlled hyperthermia test performed before and after the trial. 4 subjects served as controls. The main finding of the study was that sweat output increased 17.3%±1.5 SEM on the posttrial test, without any change in . It is concluded that moderate physical training can improve heat responses in resting man.This investigation was supported by Direction des Recherches et Etudes Techniques (Délégation Ministérielle pour l'Armement) grant No. 77/1198.The authors wish to thank Dr B. Roussel for the helpful discussions on the results of this study.     

Decreased blood PCO2 P_{CO_2 } in the ovine foetus during hyperthermia: Implications for increased placental blood flow

Zusammenfassung Bei Wärmebelastung trächtiger Schafe ergibt sich eine wahrscheinliche Zunahme der Placentardurchblutung (mütterlicher Kreislauf), welche einer erwarteten Zunahme von im foetalen Blut entgegenwirkt.     

Selective potentiating effects of metal ions on vasopressom

Zusammenfassung Der Effekt von Na⁺-, NH₄ ⁺- und Ca⁺⁺-Ionen auf die Blutdruckaktivität von Arginin-Vasopressom wurde untersucht und mit analogen Experimenten (Val⁵-Angiotensin II-Asp¹--Amid) verglichen. Die Wirkungsweise der Ionen-induzierten Potenzierung von Vasopressin wird diskutiert.

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Supported by USPHS Grant No. AM-13567.

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Abbreviations used are: AVP, arginine-vasopressin; bp, blood pres sure; U, unit;n, number of experiments; , mean value; S.E. standard error;p, level of significance; NS, not significant.     

Effects of isoxazolyl-naphthoquinoneimines on growth and oxygen radical production inTrypanosoma cruzi andCrithidia fasciculata

Several 4-(aminomethylisoxazolyl)-1,2-naphthoquinones inhibited growth and DNA synthesis inTrypanosoma cruzi and stimulated O₂ uptake and generation by the parasite epimastigotes and their mitochondrial and microsomal membranes; these results support the idea that oxygen radicals play a role in quinone toxicity. Maximal effects on respiration and generation were observed with antimycin-inhibited cells. Similar results as well as stimulation of H₂O₂ production were obtained withCrithidia fasciculata despite the presence of catalase in this organism.Acknowledgments. This work was aided by grants from the University of Buenos Aires, the Scientific Office of the American States Organization and CEDIQUIFA (Buenos Aires). S.G.G. and M.P.M.P. are Research Fellows and A.O.M.S. is Career Investigator of CONICET (Argentina). L. T. Viñas and M. G. Gutierrez lent able technical assistance.     

Increase in the survival time of mice exposed to ionizing radiation by a new class of free radical scavengers

Summary N-acyl dehydroalanines react with and scavenge mainly superoxide radical and hydroxyl radical (HO^.). The ortho-methoxyphenylacetyl dehydroalanine derivative, indexed as AD-20, protects mice against damage resulting from total body X-irradiation, as measured by the increase in their survival time. AD-20 increases the LD₅₀ at 30 days from 6.1 to 7.3 Gy in animals exposed to a wide range of X-rays (6 to 10 Gy). The dose reduction factor (D R F) of AD-20 is 1.20. We postulate that such radioprotective effect may result from its free radical scavenging activity.     

Studies of the dose-effect relation

Summary Dose-effect relations and, specifically, cell survival curves are surveyed with emphasis on the interplay of the random factors — biological variability, stochastic reaction of the cell, and the statistics of energy deposition —that co-determine their shape. The global parameters mean inactivation dose, , and coefficient of variance, V, represent this interplay better than conventional parameters. Mechanisms such as lesion interaction, misrepair, repair overload, or repair depletion have been invoked to explain sigmoid dose dependencies, but these notions are partly synonymous and are largely undistinguishable on the basis of observed dose dependencies. All dose dependencies reflect, to varying degree, the microdosimetric fluctuations of energy deposition, and these have certain implications, e.g. the linearity of the dose dependence at small doses, that apply regardless of unresolved molecular mechanisms of cellular radiation action.     

Immunological identification of human plasma3S_{\gamma _1 } -globulin as carbonic anhydrase

Résumé La -globuline, précédemment isolée du plasma humain normal, a fait l'objet d'une comparaison immunologique avec l'anhydrase carbonique B isolée à partir d'érythrocytes. L'immunoélectrophorèse en gélose et l'immunofluorescence analysée sur le tissu rénal ont montré l'identité immunologique de ces 2 protéines.     

Carboxypeptidase A,ionic strength,and the enhancement of guinea-pig complement

Zusammenfassung Potenzierung von Meerschweinchen-komplement durch niedrige Ionenkonzentration und Carboxypeptidase A zeigt, dass das Enzym seinen stärkeren Einfluss während der Bildung von EAC ausübt. Während der Immunhämolyse übte jedoch eine niedere Ionenkonzentration einen zusätzlichen fördernden Einfluss auf eine spätere Reaktion aus.     

Il punto nella terminologia matematica greca

Summary In this note we claim that the two words and , which were used in Greece to indicate the geometrical point, had both been introduced in the scientific language in the first half of the IV^th century B.C., and that they became popular independently of each other in two different cultural circles, those of philosophy and of mathematics, respectively.We propose therefore, in contrast to a conjecture by Heiberg, a new explanation for the predominance of during the golden age of Greek mathematics and for the resurgence of during the period of decadence.

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Memoria presentata da A. Seidenberg