Showing papers by "University of Sussex published in 1974"

The hitch-hiking effect of a favourable gene.

Abstract: SUMMARY When a selectively favourable gene substitution occurs in a population, changes in gene frequencies will occur at closely linked loci. In the case of a neutral polymorphism, average heterozygosity will be reduced to an extent which varies with distance from the substituted locus. The aggregate eifect of substitution on neutral polymorphism is estimated; in populations of total size 10 6 or more (and perhaps of 10 4 or more), this eifect will be more important than that of random fixation. This may explain why the extent of polymorphism in natural populations does not vary as much as one would expect from a consideration of the equilibrium between mutation and random fixation in populations of different sizes. For a selectively maintained polymorphism at a linked locus, this process will only be important in the long run if it leads to complete fixation. If the selective coefficients at the linked locus are small compared to those at the substituted locus, it is shown that the probability of complete fixation at the linked locus is approximately exp (— Nc), where c is the recombinant fraction and N the population size. It follows that in a large population a selective substitution can occur in a cistron without eliminating a selectively maintained polymorphism in the same cistron.

The Optimal Depletion of Exhaustible Resources

Abstract: 0.1. In any given economy there must be a number of commodities that enter into production and which are used up, and whose available stock cannot be increased. Examples like fossil fuels come readily to mind. It would seem reasonable to argue that in the long run the limited availability of these commodities, together with their technological importance, would begin to act as a constraint on the economy's growth potential. In fact several recent studies have laid great emphasis on this possibility.3 Although the point is an obvious one, most economic studies of the properties of long-run plans neglect it.4 In this paper, therefore, we explore in a rather preliminary way the problems that appear to arise naturally when the existence of exhaustible resources is incorporated into the study of intertemporal plans. It appears that questions in this area are hard to answer. For even in the simplest of environments where it is supposed that there is perfect foresight, one is concerned not merely with the optimal depletion of exhaustible resources but with the optimal rate of investment as well. The two must plainly be interrelated. The latter problem on its own is hard, and the combined problem is very complex. In fact it will appear in the course of the arguments that follow that intuition is not a very good guide for this joint problem. In any case, the assumption of perfect foresight is particularly dubious here since it would appear almost immediate that an investigation of intertemporal plans in the presence of exhaustible resources readily invites consideration of the possibilities of large-scale alterations in technology at dates in the future that are inherently uncertain. Moreover, it is clear that such extensive technological changes would not be achievable costlessly. In this paper, therefore, we attempt to demonstrate how one might, in a relatively simple manner, bring such considerations as these to bear on a set of questions that have generated a considerable amount of interest in recent years. 0.2. It is plain of course that the mere existence of a resource that is exhaustible is not a

Chasing behaviour of houseflies ( Fannia canicularis )

Abstract: 1. Chases in which male flies (Fannia canicularis) pursue other flies were studied by filming such encounters from directly below. Males will start to chase whenever a second fly comes within 10–15 cm (Fig. 3). 2. Throughout these chases there was a continuous relationship between the angle (θe) made by the leading fly and the direction of flight of the chasing fly, and the angular velocity of the chasing fly (ωf). This relation was approximately linear, with a slope of 20 ° s−1 per degree θe (Figs. 4–7). 3. The maximum correlation between ωf and θite occurs after a lag of approximately 30 ms, which represents the total delay in the system (Fig. 8). 4. In the region close to the chasing fly's axis (θite less than about 35 °) a second mechanism exists in which the angular velocity of the chasing fly (ωf) is controlled by the relative angular velocity of the leading fly (ωe), rather than its relative position. The ratio of ωf to ωe in this region is approximately 0.7. 5. Using the results in 2–4 above, and an empirically determined relation between the angular and forward velocities of the chasing fly, it was possible to simulate the flight path of the chasing fly, given that of the leading fly (Fig. 11). Because these simulations predict correctly the manoeuvres and outcomes of quite complicated chases, it is concluded that the control system actually used by the fly is accurately described by conclusions 2–4. 6. The physiological implications of this behaviour, and the possible function of chasing, are discussed.

Reduction and inactivation of superoxide dismutase by hydrogen peroxide

Abstract: Reactions of H2O2 with superoxide dismutase were studied by e.p.r. (electron paramagnetic resonance) spectroscopy and other methods. In agreement with earlier work, the Cu2+ of the enzyme is reduced by H2O2, although the reaction does not go to completion and its kinetics are not simple. With dilute enzyme the time for half-reduction with 9mm-H2O2 is about 150ms. It is suggested that the reaction is a one-electron reduction, involving liberation of O2−. On somewhat more prolonged exposure to H2O2, the enzyme is inactivated. For enzyme in dilute solution and over a limited range of H2O2 concentrations, inactivation is first-order with respect to enzyme and reagent, with k=3.1m−1·s−1 at 20–25°C. Inactivation is accompanied by marked changes in the e.p.r. and visible spectra and appears to be associated with destruction of one histidine residue per subunit. It is suggested that this histidine is close to the metal in the native enzyme and essential for its enzymic activity.

The mechanism of action of superoxide dismutase from pulse radiolysis and electron paramagnetic resonance. Evidence that only half the active sites function in catalysis

Abstract: 1. Detailed studies on the mechanism of the enzymic reaction of bovine superoxide dismutase were carried out by using pulse radiolysis and electron paramagnetic resonance (e.p.r.). 2. The second-order rate constant for reaction between superoxide dismutase and the superoxide ion was redetermined as (2.37±0.18)×109m−1·s−1 at 25°C. This reaction governs the turnover, and any first-order steps must have rate constants higher than about 106s−1. Turnover has a low activation energy and is slowed substantially when the viscosity is increased with glycerol, confirming that the reaction rate is near the limit for diffusion control. In water a reversible conformation change to a less active form appears to take place above about 40°C. 3. Pre-steady-state rates of reduction and reoxidation of copper in the enzyme are consistent with these processes being rate-limiting in enzyme turnover. 4. Examination, with the help of computer simulation, of the e.p.r. spectra at 9 and 35GHz of native superoxide dismutase indicated that, apart from 10–20% of impurities, only one species of Cu2+ is distinguishable. Further, the specific activity of our enzyme preparations, measured by pulse radiolysis, is at least as high as that obtained by other workers. 5. Nevertheless, measurement of the proportion of copper present as Cu2+ (determined both optically and by e.p.r. spectroscopy) in the steady states approached from both the oxidized and the reduced forms of the enzyme, indicates (after allowing for the impurities) that only half of the copper atoms participate in turnover. E.p.r. spectroscopy provided no evidence for differences between functioning and non-functioning Cu2+ atoms. 6. It is suggested that the results may be best interpreted in terms of an allosteric type of mechanism, with two initially indistinguishable copper atoms in the enzyme. Reaction of one of these with a superoxide ion then renders the other, at least transiently, unreactive.

The influence of substrate concentrations on the rate of insect juvenile hormone biosynthesis by corpora allata of the desert locust in vitro

Abstract: The rate at which isolated corpora allata of adult female Schistocerca gregaria incorporate [3H]farnesenic acid and [14C]methionine into C16juvenile hormone in vitro was examined at different concentrations of farnesenic acid, methionine, O2 and H+ ions. Maximum juvenile hormone biosynthesis is obtained at a farnesenic acid concentration of 20μm. The range of optimum l-methionine concentrations (0.1–0.4mm) encompasses the physiological concentration of this substrate in the haemolymph. Hormone biosynthesis is dependent on O2, but is not stimulated by hyperbaric oxygen tension. The glands had a maximum synthetic activity at pH8.0, but their activity was more reproducible in the the physiological range pH7.0–7.5. At pH6.5 and less, the synthetic ability was considerably decreased. The relative incorporations of the labelled substrates into methyl farnesoate and C16 juvenile hormone indicate that [3H]farnesenic acid comes into isotopic equilibrium within the gland more rapidly than [14C]methionine. The incorporations into methyl farnesoate become stoicheiometric after 20min incubation and into C16 juvenile hormone after a further 10min. Labelled juvenile hormone is detectable after 10min incubation and the rate of incorporation is constant for up to 4h. It is proposed that the described method may be usefully employed to assess the physiological changes in the enzymic competence of the glands to effect the last two stages in C16 juvenile hormone biosynthesis.

Primate social organisation and ecology

Abstract: Attempts to relate interspecific differences in social organisation among primates to gross differences in habitat or diet type have been largely unsuccessful. This is probably partly because distantly related species have adapted to similar ecological situations in different ways and partly because much finer ecological differences are important.

Effects of caffeine and theophylline on DNA synthesis in unirradiated and UV-irradiated mammalian cells.

Abstract: Summary The effects of caffeine and theophylline on the rate of DNA synthesis and on the size of newly synthesized DNA made in unirradiated and UV-irradiated rodent cell lines have been examined. The principal and most dramatic effect exerted by these methylsted xanthines was an inhibition, at relatively low doses of the drugs (0.8-1.5 m M ), of a “post-replication repair” process in UV-irradiated cells. Gaps left in daughter DNA strands opposite UV-induced pyrimidine dimers in the parental strands, are normally sealed within a few hours after their formation. In the presence of caffeine or theophylline, this gap-filling process was specifically and strongly inhibited. As a consequence, in UV-irradiated cells low molecular weight pieces 0 newly syn- thesized DNA accumulated in the presence of caffeine or theophylline, whereas in their absence, the new DNA eventually attained the size of that in unirradiated cells. In unirradiated cells, caffeine and theophylline exerted smaller effects, and higher doses (1.5 m M or more) hacl to be used. At these high doses, DNA synthesis was inhibited and the newly synthesizecl DNA was made in smaller units than in untreated cells. Both the integrity and the repair of pre-existing DNA were unaffected by caffeine, These results may account for the well-documented sensitization of cells to UV light by caffeine and theophylline, and for the observations that caffeine exerts many of its cytological effects in cultured mammalian cells only if it is present during the DNA synthesis period.

Glutamine synthetase and ammonium regulation of nitrogenase synthesis in Klebsiella

Abstract: Glutamine synthetase seems to act as a positive control element for nitrogenase synthesis in a way similar to that already proposed for histidase synthesis in Klebsiella. Studies along lines opened up by these findings may provide answers to many of the problems in establishing nitrogen fixation in non-leguminous plants.

Factors for Success in Industrial Innovation

Abstract: Considering the enormous amount of resources (cash, materials, qualified manpower) expended annually in the advanced countries on research and development much of which, presumably, is aimed at producing commercially exploitable goods and processes, it is surprising how miniscule is the effort which has gone into studying the process by which this exploitation° occurs, i.e. the innovation processt. There is, of course, an extensive literature available concerning, for example, R & D project selection and evaluation techniques, marketing methods, production procedures, and the like, but these are all specific innovation sub-pt_ocesses, and there is generally no attempt at cross linkage between, or integration of, these various sub-processes to consider the total process of innovation. A simplified schematic model of the innovation process, showing a number of sub-processes, is given in Fig. 1. One effective method for studying the do's and don'ts and the why's and wherefores of innovation is through the retrospective analysis of actual attempts at innovating: here, the complete innovation process is considered. Obviously the wider the scope of the investigation, the more suitable are the · results of that investigation for generalization. Since the late 1950's a number of studies have been undertaken

Experiments in the formulation of integer programming problems

Abstract: Five practical problems are each formulated in two different ways as 0–1 integer programming models. All the models have been solved by the Branch and Bound method using a commercial package program. Full details are given of the manner of the different formulations and the computational ease of solving them. The purpose of this paper is to investigate the computational effects of different formulations on such problems. The problems considered are a market allocation problem, a combinatorial problem, two mining problems and a problem of logical design.

Mössbauer spectroscopy of the nitrogenase proteins from Klebsiella pneumoniae. Structural assignments and mechanistic conclusions

Abstract: The Mo-Fe protein and the Fe protein which together constitute the nitrogenase of Klebsiella pneumoniae were prepared from bacteria grown in (57)Fe-enriched medium. The Mossbauer spectrum of the Mo-Fe protein, as isolated in the presence of Na(2)S(2)O(4), showed that the protein contained three iron species, called M4, M5 and M6. The area of the spectrum associated with species M4, with delta=0.65mm/s and DeltaE=3.05mm/s at 4.2 degrees K, corresponded to two iron atoms/molecule of protein and it is interpreted as being due to a high-spin ferrous, spin-coupled pair of iron atoms. The iron atoms of species M4 may be involved in the quaternary structure of the protein. Species M5, with delta=0.61mm/s and DeltaE=0.83mm/s at 77 degrees K, corresponded to eight iron atoms/molecule of protein and is interpreted as being due to Fe(4)S(4) or Fe(2)S(2) low-spin ferrous iron clusters. Species M6, with delta=0.37mm/s and DeltaE=0.71mm/s at 77 degrees K, also corresponded to eight iron atoms/molecule of protein and, at 4.2 degrees K, became a broad shallow absorption, characteristic of magnetic hyperfine interaction. Oxidation of the Mo-Fe protein with the redox dye Lauth's Violet did not affect the activity of the protein but changed species M4, M5 and M6 into the species M1 (delta=0.37mm/s, DeltaE=0.75mm/s at 77 degrees K, broad magnetic component at 4.2 degrees K) and M2 (delta=0.35mm/s, DeltaE=0.9mm/s at 4.2 degrees K). In the presence of the Fe protein, Na(2)S(2)O(4), ATP and Mg(2+), the M6 component of the Mo-Fe protein was replaced by species M7 with delta=0.46mm/s, DeltaE=1.04mm/s at 4.2 degrees K. The change in Mossbauer parameters associated with the M6 --> M7 transformation was very similar to the change observed on reduction of the high-potential Fe protein from Chromatium vinosum. In contrast, Na(2)S(2)O(4)-reduced Fe protein contained only one type of iron cluster (F4). Species F4 had delta=0.50mm/s, DeltaE=0.9mm/s at 195 degrees K, and at 4.2 degrees K broadened in a manner characteristic of a magnetic hyperfine interaction, associated with half-integral spin, equally distributed over all four atoms of the Fe protein. The Mossbauer spectra of the Mo-Fe and the Fe protein under argon were unaffected by the reducible substrates N(2) and C(2)H(2) and the inhibitor CO in the presence of ATP, Mg(2+) and Na(2)S(2)O(4). A number of Mossbauer spectral species associated with inactivated Mo-Fe and Fe proteins are described and discussed.

The Structure of the Diatomic Molecular Solids

Abstract: A simple model of the low temperature phases of the diatomic molecular solids is examined. The model consists of molecules, interacting via a Lennard-Jones atom-atom potential and quadrupole-quadrupole interactions. The internal energy of any crystallographic structure (excluding thermal effects) can then be given in terms of two dimensionless parameters, which describe the deviation of the molecular shape from a sphere and the relative importance of the quadrupole energy. The minimum energies and optimum molecular configurations in several structures are computed, for values of these dimensionless variables which span the values appropriate to the actual homonuclear diatomic molecular solids, H$\_{2}$, N$\_{2}$, O$\_{2}$, F$\_{2}$, Cl$\_{2}$, Br$\_{2}$ and I$\_{2}$. Despite its great simplicity, the model is able to explain several features of these structures. These are (i) $o-\text{H}\_{2}$ and N$\_{2}$ have the optimum quadrupole structure, Pa3; (ii) $\beta $-O$\_{2}$ is one of the optimum van der Waals' structures, R$\overline{3}$m; (iii) the monoclinic $\alpha $-F$\_{2}$ structure is the most stable structure for parameter values very close to those appropriate to F$\_{2}$; (iv) the orthorhombic Cmca structure (observed for Cl$\_{2}$, Br$\_{2}$ and I$\_{2}$ is the most stable structure for a large range of quadrupole moments which may be appropriate to these molecules. The model, is, of course, unable to take into account intermolecular bonding or spin-dependent interatomic forces. The former is important for the halogens and the latter for the (magnetic) oxygen molecule. The case of $\alpha $-O$\_{2}$ is treated in the following paper.

Effect of growth conditions on the activity of ornithine decarboxylase in cultured hepatoma cells. I. Effect of amino acid supply

Abstract: Ornithine decarboxylase activity in high density, stationary phase rat hepatoma (HTC) cells in suspension culture has an extremely short half-life of between 5 and 15 minutes, as measured after inhibiting protein synthesis Following dilution of these cells into fresh medium there is a large increase in ornithine decarboxylase activity, reaching a peak often several hundred times the initial level at about four hours At least part of this stimulation is due to an increase in the apparent half-life of the enzyme, to between 30 and 90 minutes Evidence is presented that the supply of amino acids can control the turnover of ODC under some conditions For example supplementing high density cells with glutamine, asparagine, serine, glycine and proline, either singly or together, increases ODC activity and decreases its apparent turnover The stimulation by amino acids is enhanced by serum

The three-tier approach to mt1tagenicity screening and the concept of radiation-equivalent dose

Abstract: Summary A three-tier approach to mutagenicity screening is proposed, based on 3 general principles. The first tier consists of in vitro tests which would be the only tests to which compounds not intended for direct ingestion would be subjected, for example industrial chemicals. Substances intended for ingestion ( e.g. food additives and medicines) together with other widespread substances that might be expected to accumulate within the body would, if they give negative results in the first tier tests, would be subjected to a second tier of in vivo tests using whole mammals. Substances giving positive results in either of these tests would pass to a third tier of evaluation. Here the object would be to carry out experiments designed to give a quantitative indication of the potential risk to man followed by a risk-benefit assessment. It is suggested that one way of comparing the effect of one agent with that of another might be to express it as a radiation-equivalent dose (in radeguiv units).

Respiration and Nitrogen Fixation in Azotobacter

Abstract: Publisher Summary The chapter focuses on the work done toward this aspect; toward understanding how respiration and nitrogen fixation can function simultaneously in Azotobacter. Accordingly, only those aspects of this subject that are connected with the physiology of nitrogen fixation in aerobes will be discussed. In particular, determination of the constitution and behavior of this organism's branched respiratory chain has contributed to the understanding of how respiration controls nitrogen fixation. All nitrogenases from both aerobic and anaerobic organisms comprise two non-haem iron proteins, which have the same requirements for enzymic activity in vitro— namely, an anaerobic environment, a source of ATP, and a reluctant. The two component proteins that make up the nitrogenase enzyme complement each other in cross reactions between nitrogenase fractions from aerobic and some anaerobic sources and physiological electron carriers from one class of bacteria can donate electrons to nitrogenase from the other. The absence of oxygen is mandatory in nearly all measurements of nitrogen fixation in vitro. Crude preparations that show nitrogenase activity in the presence of oxygen have been obtained from aerobic nitrogen fixers. From the foregoing evidence it is reasonable to assume that nitrogen fixation is an anaerobic process catalyzed by oxygen-sensitive proteins. How these operate and survive in an aerobic bacterium is discussed in detail. Because oxygen uptake is the major electron-utilizing metabolic process in Azotobacter, the respiratory chain involving electron transport and oxidative phosphorylation are described.

A computer simulation study of Hertzian cone crack growth

Abstract: A general method for simulating on a computer the growth of the cone-shaped fracture that forms under Hertzian contact loading is outlined The program involves an incrementing procedure in which both contact circle and cone crack are grown in piecewise manner, according to suitable rate equations The contact circle expands at a rate determined by the mode of indenter loading, and thereby sets up a time-varying stress field Appropriate fracture-mechanics criteria are then invoked to calculate the response of the growing crack to the contact stresses Effects of loading mode, specimen environment and temperature, size and location of the initial flaw from which the cone crack nucleates, are investigated systematically The computer predictions compare favourably with available experimental data The results are discussed in the light of previous theoretical treatments of the Hertzian fracture problem, and some new features in the crack-growth characteristics are pointed out Calculations are made specifically for normal contact loading on glass, but ready extension of the program to other loading situations and materials in envisaged