Kinship and covariance

Price's (1970) covariance theorem can be used to derive an expression for gene frequency change in kin selection models in which the fitness effect of an act is independent of the genotype of the recipient. This expression defines a coefficient of relatedness which subsumes r(Wright, 1922), b(Hamilton, 1972), ρ (Orlove &; Wood, 1978), and R(Michod &; Hamilton, 1980). The new coefficient extends the domain of Hamilton's rule to models in which the average gene frequency of actors differs from that of recipients.     

An approach to a physico-chemical model of olfactory stimulation in vertebrates by single compounds

During recent years, numerous attempts have been made to correlate both quantitative (Davies &; Taylor, 1959; Engen, 1962; Beck, 1964; Engen, Cain &; Rovee, 1968; Cain, 1969; Dravnieks &; Laffoit, 1970; Laffort, 1969a,b) and qualitative (Davies, 1965; Amoore &; Venstrom, 1965; Döving, 1966a,b; Wright &; Michels, 1964; Leveteau &; MacLeod, 1969) odorous properties of single compounds to their molecular properties. These attempts have been only partially successful.In the present paper we will try to explain the several odorous properties of single compounds on the basis of the non-specific properties of odorants involved in solubility.This model is a first approach, and although it gives statistically highly significant relations, it is not as accurate as those advanced with respect to the physical and sensory dimensions of stimuli in the fields of vision and audition.We will first give the present definitions of the most suitable physicochemical parameters, and then advance quantitative and qualitative models for single compounds. Quantitative odorous properties are: odour threshold, rate of change of odour intensity with odorant concentration in the suprathreshold region, and the somewhat controversial upper odour intensity. Qualitative properties refer to odour character.     

Trehalose-6-phosphate synthetase activity in extracts of Dictyostelium discoideum.

Trehalose-6-phosphate (T-6-P) synthetase activity in extracts of Dictyostelium discoideum has been reexamined in an effort to resolve discrepancies between the results of previous studies (R. Roth and M. Sussman (1966). Biochim. Biophys. Acta, 122, 225; K. A. Killick and B. E. Wright (1972). J. Biol. Chem., 247, 2967). We find that T-6-P synthetase is not cold sensitive as reported by Killick and Wright (1972), is not present in bacterial-grown vegetative cells (though subject to some modulation by other nutritional conditions), and is not in our hands unmasked or activated by ammonium sulfate fractionation. We conclude that the pattern of T-6-P synthetase accumulation and disappearance during fruiting body construction in D. discoideum is as originally described by R. Roth and M. Sussman (1968). J. Biol. Chem., 243, 5081) and confirmed elsewhere (P. C. Newell et al. (1972). J. Mol. Biol., 63, 373; R. W. Brackenbury et al. (1974). J. Mol. Biol., 90, 529; B. D. Hames and J. M. Ashworth (1974). Biochem. J., 142, 301).     

Dinucleotide fold proteins. Interaction of arabinose binding protein with Cibacron Blue 3G-A.

Cibacron Blue 3G-A, the dye moiety of Blue dextran-Sepharose, has been shown to not specifically bind a protein with a dinucleotide fold-like supersecondary structure, L-arabinose binding protein from Escherichia coli. This shows that Cibacron Blue 3G-A is not suitable as a definitive probe for the dinucleotide fold as suggested earlier (Thompson et al., 1975; Stellwagen, 1977). An explanation for the large predominance of proteins containing this protein supersecondary structure that bind to this dye is presented.     

Proteolysis in eucaryotic cells: Aminopeptidases and dipeptidyl aminopeptidases of yeast revisited

Using nine different l-aminoacyl-4-nitroanilides and four different dipeptidyl-4-nitroanilides, aminopeptidases and dipeptidyl aminopeptidases active at pH 7.5 and (or) pH 5.5 in logarithmically growing and stationary-phase cells of Saccharomyces cerevisiae were searched for. Ion-exchange chromatography was used to separate the proteins of the soluble cell extract. Besides the three already-characterized aminopeptidases—aminopeptidase I (P. Matile, A. Wiemken, and W. Guyer (1971) Planta (Berlin)96, 43–53; J. Frey and K. H. Röhm (1978) Biochim. Biophys. Acta527, 31–41), aminopeptidase II (J. Frey and K. H. Röhm (1978) Biochim. Biophys. Acta527, 31–41; J. Knüver (1982) Thesis, Fachbereich Chemie, Marburg, FRG), and aminopeptidase Co (T. Achstetter, C. Ehmann, and D. H. Wolf (1982) Biochem. Biophys. Res. Commun.109, 341–347)—12 additional aminopeptidase activities are found in soluble cell extracts eluting from the ion-exchange column. These activities differ from the characterized aminopeptidases in one or more of the parameters such as charge, size, substrate specificity, inhibition pattern, pH optimum for activity and regulation. Also, a particulate aminopeptidase, called aminopeptidase P, is found in the nonsoluble fraction of disintegrated cells. Besides the described particulate X-prolyl-dipeptidyl aminopeptidase (M. P. Suarez Rendueles, J. Schwencke, N. Garcia-Alvarez and S. Gascon (1981) FEBS Lett.131, 296–300), three additional dipeptidyl aminopeptidase activities of different substrate specificities are found in the soluble extract.     

The role of migration in the genetic structure of populations in temporally and spatially varying environments II. Island Models

The Island Model introduced by Sewall Wright (1951) has proven to be a useful construction for studying the interaction of genetic drift, population subdivision, and mutation. Interest in the model has recently increased because of its relevance to certain questions involving the rate of differentiation of sub-populations under the neutral allele hypothesis (e.g., Smith, 1970; Latter, 1973). It is perhaps the only realistic population structure in which the test for neutrality proposed by Lewontin and Krakauer (1973) is valid (Lewontin and Krakauer, 1975). If data from natural populations is to be compared to the predictions of the Island Model, it is desirable to have an alternative model with the same migration pattern but with natural selection operating. In this paper one such model will be introduced where the stochastic element comes from random fluctuations in the environment rather than from genetic drift. The model is a direct extension of the one in the previous paper in this series (Gillespie, 1975) which dealt with a population which is subdivided into two patches with restricted migration between them.     

The Plasmodium vaughani--Complex

Plasmodium vaughaniNovy and MacNeal, 1904, Plasmodium tenueLaveran and Marullaz, 1914, and Plasmodium merulaeCorradetti and Scanga, 1972 are shown to differ. It is suggested that P. tenue and P. merulae should be considered as subspecies belonging to Plasmodium vaughani-complex.More investigations are needed for a sufficient knowledge of the complex, particularly because at least 36 species of birds harbor P. vaughani-like parasites and cover an immense geographical area in all the parts of the world.     

An autoradiographic analysis of the time of appearance of neurons in the developing chick neural retina

The pattern of incorporation of [³H]thymidine into the chick neural retina has been used to establish the time and order in which different classes of neuroepithelial cells withdraw from the cell cycle and initiate migration and differentiation.The posterior pole of the retina is the first to form during development. In this region most neuroepithelial cells complete mitotic activity between the third and sixth day of incubation. Presumptive ganglion cells initiate the withdrawal process, and they are soon followed by the neuroepithelial precursors of amacrine, horizontal, and receptor cells. Bipolar cell precursors are the last to begin and the last to complete cell cycle activity. It is worthy of note, however, that, in any given region of the retina, neuroepithelial cells of all types cease mitosis in close, overlapping succession.These results are in reasonable agreement with those previously published on the chick retina by Fujita and Horii (1963), and other investigators on the mouse (Mus), killifish (Fundulus), and toad (Xenopus). The present data are also consistent with those proposals of Angevine (1970), Jacobson, 1968a, Jacobson, 1968b, Jacobson, 1970, and others that relate the cessation of mitotic activity of neuroepithelial cells to the determination of neuronal size, axon length, and the specification of neuronal connections.     

Fusion of chick embryo skeletal myoblasts: interactions of prostaglandin E1, adenosine 3':5' monophosphate, and calcium influx

In the accompanying paper (J. D. David, W. M. See, and C.-A. Higginbotham, 1981, Develop. Biol.82, 297–307) we demonstrated that a net calcium influx into fusion-competent myoblasts is a requisite step in membrane fusion. Zalin and Montague, 1974, Zalin, 1977 has shown that a prostaglandin E₁ (PGE₁)-dependent transient rise in cAMP occurs 5–6 hr prior to myoblast fusion. In this communication we show that (1) the increase in intracellular cAMP precedes, and/or is independent of, the calcium influx; (2) the calcium influx is either directly or indirectly dependent on PGE₁ activity as well as PGE₁ synthesis; and (3) although the cAMP increase may be essential for fusion, it is not sufficient in the absence of calcium influx. Our experiments define fusion competency, at a minimum, as (1) the accumulation of extracellular PGE₁ receptors; (2) the accumulation of intracellular cAMP receptors; and (3) the ability to respond to a calcium influx.     

Box-Jenkins forecasting in ecology: An answer to poole

This answering of Poole, 1978, Poole, 1976 aims at rounding off our exchange of views, without losing the readership from an excess of toing and froing between the four contributions. So my final rejoinder only attempts at treating the general points raised by Poole (1978), rather than taking issue with all the minutiae, which would require too many quotes of quotes and counterquotes. The main nub of contention remains as to whether or not statistical fits can be meaningfully interpreted biologically.     

A mechanism for the hydrolysis of MgATP by actomyosin of skeletal muscle.

Based on a model of the active site of myosin (Ramirez, Shukla &; Levy, 1978), a chemical mechanism for MgATPase and intermediate oxygen exchange is presented. In this mechanism, oxygen exchange takes place via an oxyphosphorane intermediate that undergoes double turnstile rotation (Ugi, Ramirez, Marquarding, Klusacek &; Gillespie, 1971; Ramirez &; Ugi, 1974. During hydrolysis by native skeletal muscle myosin, only three [¹⁸O] atoms from labelled water are rapidly incorporated into the phosphorus that is finally released to the medium as P_i; whereas, during hydrolysis by subfragment 1 (S1), which is the head of myosin, four oxygens are labelled rapidly. To explain this difference, we postulate that cleavage of the (S1)-(S2) hinge in the preparation of S1 modifies the interaction of the oxyphosphorane intermediate at the active site. This enables a normally non-exchangeable oxygen to enter the exchange process. This is consistent with our earlier interpretation to the effect that the active site and the hinge in myosin are relatively close to each other Shukla &; Levy, 1977b; Shukla &; Levy, 1978. We postulate that the major elements of the active site are situated on a 92 amino acid fragment, p₁₀, isolated by Elzinga &; Collins, 1977 from myosin. P₁₀ is now known to be situated in the region that connects the head to the body of a myosin heavy chain (Lu, Sosinki, Balint &; Streter, 1978). An examination of the p₁₀ fragment for a possible point of proteolytic attack in the region of the hinge which will generate S1 revealed lysine 82. Breaking the protein chain at a point so close to the active site pocket could explain the effect of hinge cleavage on oxygen exchange. Two additional features of the present mechanism are: (1) the protonation of P_γ of a MgP_α,P_γ complex of ATP, which depresses monomeric metaphosphate mediated hydrolysis, and enhances oxyphosphorane formation by addition of water to P_γ; (2) the coordination of N^τ-methylhistidinet² of actin with Mg at the active site, which activates the release of the products of hydrolysis.     

Complexity-stability relationship of two-prey-one-predator species system model: Local and global stability

Parrish & Saila (1970), motivated by the experiments of Paine (1966), constructed a simple mathematical model for a two-prey-one-predator system. They were unable to find, in their model, a set of parametric values with which the three-species system can be stable, whereas a twoprey species system without a predator is unstable. Cramer & May (1972) showed that, in fact, such parametric values exist, and gave the necessary mathematical condition. I have investigated the complete conditions for the stability of the system around the equilibrium point, and show that the conditions must be more stringent than given by Cramer & May (1972). Also, it is shown that the present model can have a globally stable limit cycle in three species even when the equilibrium point is locally unstable.     

Iron-ethylenediaminetetraacetic acid (EDTA)-catalyzed superoxide dismutation revisited: An explanation of why the dismutase activity of Fe-EDTA cannot be detected in the cytochrome c/xanthine oxidase assay system

The recent assertion of J. Diguiseppi and I. Fridovich (1980, Arch. Biochem. Biophys., 203, 145–150) that Fe-EDTA does not catalyze superoxide dismutation is disputed. By directly observing superoxide generated during pulse radiolysis, we have confirmed the results of a previous study (G. J. McClune, J. A. Fee, G. A. McClusky, and J. T. Groves, 1977, J. Amer. Chem. Soc., 99, 5220–5222) which concluded that Fe-EDTA catalyzed superoxide dismutation. We also demonstrate that the reaction of Fe(II)-EDTA, formed during catalyzed superoxide dismutation, with cytochrome c, the probe molecule in the cytochrome c/xanthine oxidase/xanthine assay system for superoxide dismutase activity, is sufficiently rapid (H. L. Hodges, R. A. Holwerda, and H. B. Gray, 1974, J. Amer. Chem. Soc., 96, 3132–3137) to obscure the weak catalysis of superoxide dismutation by Fe-EDTA.     

A note on the sampling theory for infinite alleles and infinite sites models

This note considers sampling theory for a selectively neutral locus where it is supposed that the data provide nucleotide sequences for the genes sampled. It thus anticipates that technical advances will soon provide data of this form in volume approaching that currently obtained from electrophoresis. The assumption made on the nature of the data will require us to use, in the terminology ofKimura (Theor. Pop. Biol.2, 174–208 (1971)), the “infinite sites” model of Karlin and McGregor (Proc. Fifth Berkeley Symp. Math. Statist. Prob.4, 415–438 (1967)) rather that the “infinite alleles” model of Kimura and Crow (Genetics49, 174–738 (1964)). We emphasize that these two models refer not to two different real-world circumstances, but rather to two different assumptions concerning our capacity to investigate the real world. We compare our results where appropriate with corresponding sampling theory of Ewens (Theor. Pop. Biol.3, 87–112 (1972)) for the “infinite alleles” model. Note finally that some of our results depend on an assumption of independence of behavior at individual sites; a parallel paper byWatterson (submitted for publication (1974)) assumes no recombination between sites. Real-world behavior will lie between these two assumptions, closer to the situation assumed by Watterson than in this note. Our analysis provides upper bounds for increased efficiency in using complete nucleotide sequences.     

Does a functional relationship exist between the polymerization and catalytic activity of beef liver glutamate dehydrogenase?

The recent work of Cohen &; Benedek (1976) and Cohen et al. (1975, 1976) on the apparent interdependence of beef liver glutamate dohydrogenase catalytic activity and degree of polymerization is examined in the light of previously published equilibrium and kinetic results. It is shown that some of the hypotheses central to the Cohen &; Benedek (1976) model are in contradiction with existent data. Consideration of all available information leads to the conclusion that effector-induced depolymerization may simply be an incidental side reaction in the events leading to inhibition.     

Theory of radiation dose-survival curves for the case where organism lethality is defined as loss of reproductive capacity. II. Application to cells and physical interpretation

The general theory of survival curves (Craig, 1971) is applied to the case of cells and sub-cellular organisms with a physical interpretation via gene or chromosome damage as the terminal lesion.It is indicated how the proposed terminal lesion is consistent with the salient features of cellular response to radiation and analytical expressions for reactivity and sensitivity in terms of a damage, or mutation, cross section are obtained.The probability of a complex cross section and conditions under which it reduces to simple approximations are discussed and the influence of various factors on the cross section are indicated.Acceptable fits are obtained to the data of Barendsen, Beusker, Vergroesen &; Budke (1960), McCulloch &; Till (1962) and Puck &; Marcus (1956) with simple forms of cross section.     

Immortal fibroblasts?

Uncommitted fibroblasts may exist (Kirkwood &; Holliday, 1975; Holliday, Huschtscha, Tarrant &; Kirkwood, 1977). I show that, even if such cells divide significantly faster than committed ones, the uncommitted cells would be overlooked if one uses current culture techniques. Some general guidelines for testing the model are outlined. Uncommitted cells would be useful in studying the biochemical mechanisms of aging and development.     

Cell surface glycosyltransferase activities during normal and mutant (TT) mesenchyme migration

Migrating cells possess surface glycosyltransferase activity toward extracellular substrates, and the appearance of enzyme activity coincides with the onset of cellular migration (Shur, 1977a, Shur, 1977b, Develop. Biol.58, 23–39, 40–55; E. A. Turley and S. Roth, 1979, Cell17, 109–115). In this paper, surface glycosyltransferases were examined during normal and $\text{T}\text{T}$ mutant mesenchyme migration. Of six glycosyltransferases that were assayed, only galactosyltransferase was present at significant levels on the cell surface, despite the presence of a variety of intracellular glycosyltransferases. All controls have been performed to show clearly the enzyme activity was cell surface localized. In both normal and $\text{T}\text{T}$ embryos, surface galactosyltransferase activity was localized, by autoradiography, primarily to migrating mesenchymal cells, and to a lesser degree, to presumptive neural epithelium. During primitive streak formation, putative $\text{T}\text{T}$ embryos were devoid of surface galactosyltransferase activity. However, as development progressed, the $\text{T}\text{T}$ level of activity eventually exceeded wild-type levels by two- to sixfold and was evident in $\text{T}\text{T}$ tissues prior to the onset of microscopic pathology. Other surface enzymes assayed did not show any $\text{T}\text{T}\text{-}\text{dependent}$ increase in activity. The extracellular galactosyl acceptors were not chloroform:methanol soluble, and glycopeptides prepared by exhaustive Pronase digestion were excluded from Sephadex G-50. This large galactosylated glycoconjugate was readily digestable with endo-β-galactosidase, and, therefore, is similar to the poly-N-acetyllactosamine chains previously identified on early embryonic tissues (A. Kapadia, T. Feizi, and M. J. Evans, 1981, Exp. Cell. Res.131, 185–195; T. Muramatsu, G. Gachelin, M. Damonneville, C. Delarbre, and F. Jacob, 1979, Cell18, 183–191; A. Heifetz, W. J. Lennarz, B. Libbus, and Y. -C. Hsu, 1980, Develop. Biol.80, 398–408). These results support an involvement of surface galactosyltransferases in mesenchyme formation and during migration on poly-N-acetyllactosamine substrates.