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.     

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.     

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.     

Warfare and hominid brain evolution.

This paper reviews literature on the evolutionary effects of warfare upon the hominid brain. Alexander &; Tinkle (1968) and Bigelow (1969) are found to be the first to propose that warfare was the principle evolutionary pressure that created the novel substance of the human brain, and that it acted at least from the early Pleistocene. These writers are distinguished from Darwin (1871), Keith (1947) and Wilson (1975) who saw warfare influencing the development of the brain only in historical or near-historical times.The warfare hypothesis of Alexander &; Tinkle is found to be an excellent explanation of the evolution of the human brain, but to be unsatisfactory from a biological viewpoint because they do not explain how warfare evolved in the first place, nor do they attempt to account for the apparent absence of warfare as a behavioral adaptation in species other than some eusocial insects.This author underpins the warfare hypothesis, arguing that it evolved as a necessary consequence of the circumstances of early hominids. Proficient tool use gave domination over predators and opened up new food resources, thereby diminishing two population controls. A population explosion resulted and, at critical densities, when starvation threatened, warfare was the genetically most successful behavioral adaptation. Alternative hypotheses are shown to be inadequate. Finally, the author asks why such an important hypothesis has been ignored for almost a decade.     

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.     

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.     

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.     

Xylidine isomers. VII. Structure-hepatotoxic activity relationships of some xylidines

Hepatotoxic studies of xylidines differ with regard to the animal species and type of isomer. The aim of the present paper is to correlate electronic structure data and physical-chemical properties, studied by the authors during a few previous papers (Sahini & Weinberg, 1973; Sahini, Weinberg & Vasilescu 1976, Weinberg & Sahini, to be published; Weinberg & Sahini, 1980), with the hepatotoxic activity of xylidines. Two possible biochemical mechanisms are advanced by help of correlation equations.     

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.     

A general theory of chromosome pairing based on the palindromic DNA model of Sobell with modifications and amplifications

A model for chromosome pairing is presented. It is based on the presence of segments of symmetric sequences of bases (palindromes) in the DNA at specific places in the chromosome. Palindromic DNA has been characterized by Wilson &; Thomas (1974), who state that these sequences are a regular feature of eukaryotic DNA. Sobell (1972) has suggested that they may be involved in synapsis and genetic recombination. Sobell's model is modified and amplified in an attempt to develop a general theory of chromosome pairing that explains congressional pairing, synapsis, non-homologous pairing, the initiation of crossing over, and interference.     

The fine structure of Ameson pulvis (Microspora,Microsporida) and its implications regarding classification and chromosome cycle

Nosema pulvisPerez, 1905, Ameson pulvis (Perez) Sprague, 1977, in muscles of the crabs Carcinus maenas and C. mediterraneus from the coast of France, was observed with the electron microscope. It was found to be structurally similar to the type species A. michaelis (Sprague, 1970). Sprague, 1977, having moniliform sporogonial plasmodia, unikaryotic sporoblasts, and hirsute sporulation stages. It is treated as distinct from A. michaelis because it has slightly smaller spores (by comparison with syntype material of A. michaelis) and appears to have fewer coils in the polar filament. The results require the removal of the genus Ameson from the family Nosematidae Labbé, 1899, where Sprague (1977) had placed it under the erroneous supposition that its sporoblasts are diplokaryotic. Ameson is transferred to family Unikaryonidae Sprague, 1977. Ameson is distinguished from PereziaLéger and Duboscq, 1909, shown by Ormieres et al. to have a similar developmental pattern, by presence of appendages on its sporulation stage. A. nelsoni (Sprague, 1950), the third, and only other species of Ameson, lacks the appendages and is transferred to genus Perezia.     

Force-velocity relationship in single muscle fibres

In recent papers, it has been shown experimentally that the force-velocity relationship in single muscle fibres presents deviations from hyperbolicity at high values of the load (Edman, Mulieri & Scubon-Mulieri, 1976; Edman & Hwang,1977). It has been shown independently and on theoretical bases, that the parameter “b” in Hill's characteristic equation also presents deviations from its normal value at low values of the speed of shortening, i.e. at high values of the load (Morel, Pinset-Härström & Gingold, 1976). In the present paper, it is shown that both the experimental and the theoretical results are in excellent agreement and a theoretical force-velocity relationship is proposed.     

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.     

Replication of a mammalian genome: the role of de novo protein biosynthesis during S phase

ts14 is a temperature-sensitive Chinese hamster lung cell mutant that ceases protein biosynthesis within a short time of transfer to nonpermissive temperature (Haralson and Roufa, 1975; Roufa and Haralson, 1975; Roufa and Reed, 1975). This mutant contains a revertible, presumably a point mutation that renders its 60S ribosomal subunit thermolabile (Haralson and Roufa, 1975). In this report, we describe the relationship between the conditional ability of ts14 to synthesize protein during S phase and the replication of its DNA.After transfer to nonpermissive temperature (39°C), where ts14 synthesizes protein at a rate approximately 20 fold less than wild-type cells, synchronous cultures of the mutant performed all the processes required for replication of their DNA. During prolonged incubations at nonpermissive temperature, S phase ts14 completed approximately one round of DNA replication semi-conservatively as judged by density-transfer experiments. Pulse-labeling experiments performed on S phase cells revealed that ts14 synthesized the intermediates of discontinuous DNA replication at nonpermissive and permissive temperatures at similar rates. In these tests, the mutant was not substantially different from wild-type at both culture temperatures. At the nonpermissive temperature, however, ts14 synthesized significantly less nuclear protein (that is, histone) than did wild-type cells, and the mutant's chromatin appeared deficient in histone by virtue of its increased sensitivity to nuclease.     

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.     

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.     

A stochastic model of animal growth

The plasticity of growth of animals in time, due to the resilience of their response to the ways they can be fed, suggests the difficulty of describing growth by a stochastic model in the time domain. A model is presented which avoids this difficulty by describing growth as a Markov process in the food-consumed domain, assuming that, at conception, (1) the maximum mature weight as a number α of biomass units of mass μ, and (2) the probability B of production of a biomass unit per unit of food consumed, are specified. Constancy of α, μ and B, as the animal feeds, is the basis of the proposed Markov process. The mean growth from infancy to maturity in the food-consumed domain is then the old law of diminishing returns empirically formulated first by Spillman (1924) for cattle and swine, and confirmed by Titus, Jull &; Hendricks (1934) for fowl, and by Parks (1972) across species from mice to steers. The solution also leads to the possibility that the distribution of weights in a population of growing animals of the same species, is related to the distribution of mature weights among the individuals. An experiment by Lister &; McCance (1967) with well-fed and severely undernourished pigs, shows the stability of growth in the foodconsumed domain compared to the plasticity in the time domain. Other implications of the model are discussed.     

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).