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M Pagel

Publications and source records attributed to M Pagel.

At least 19 recordsLinked to original sources
PubMed1999

Mass spectrometric analysis of benzoylated sialooligosaccharides and differentiation of terminal alpha 2-->3 and alpha 2-->6 sialogalactosylated linkages at subpicomole levels.

Perbenzoylated sialooligosaccharides were found to be stable derivatives, giving intense signals during the matrix-assisted laser desorption/ionization (MALDI) mass spectrometric analysis in the positive-ion mode. Terminal Neu5NAc alpha 2-->3 and alpha 2-->6Gal units of oligosaccharides undergo characteristic structural changes during benzoylation, yielding easily recognizable mass spectral patterns. Subpicomole carbohydrate samples were successfully benzoylated and analyzed through MALDI mass spectrometry.

Benzoates↗
PubMed1999

Inferring the historical patterns of biological evolution.

Phylogenetic trees describe the pattern of descent amongst a group of species. With the rapid accumulation of DNA sequence data, more and more phylogenies are being constructed based upon sequence comparisons. The combination of these phylogenies with powerful new statistical approaches for the analysis of biological evolution is challenging widely held beliefs about the history and evolution of life on Earth.

Animals↗
PubMed1999

Retaliatory cuckoos and the evolution of host resistance to brood parasites.

We present a dynamic model of the evolution of host resistance to avian brood parasites, when the latter can retaliate against hosts that reject parasitic eggs. In a verbal model, Zahavi (1979, American Naturalist, 113, 157-159) suggested that retaliatory cuckoos might prevent the evolution of host resistance by reducing the reproductive success of rejecter hosts (i.e. by destroying their eggs or nestlings). Here we develop a model based on the association between the great spotted cuckoo, Clamator glandarius, and its main host, the European magpie, Pica pica, because this is the only system that has provided supportive evidence, to date, for the existence of retaliatory behaviour. Our aims were (1) to derive the conditions for invasion of the retaliation strategy in a nonretaliatory parasite population and (2) to investigate the consequences of retaliation for the evolution of host defence. If we assume a cost of discrimination for rejecter hosts in the absence of parasitism, and a cost paid by a retaliator for monitoring nests, our model shows cyclical dynamics. There is no evolutionarily stable strategy, and populations of both hosts and parasites will cycle indefinitely, the period of the cycles depending on mutation and/or migration rate. A stable polymorphism of acceptors and rejecters occurs only when parasites are nonretaliators. The spread of retaliator parasites drives rejecter hosts to extinction. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1998

Developmental stability and signalling among cells.

The production of stable phenotypes depends from the earliest stages of development upon high levels of somatic cellular selection amongst cells or cell lineages. The signals exchanged amongst cells can reveal important aspects of a cell's phenotype, and might thereby be used in darwinian processes of developmental selection. Based upon an optimality model, we suggest that stable phenotypes require a substantial investment in two mechanisms of inter-cellular selection: "quality-selection" mechanisms regulate the average phenotype of a group of cells; "stability-selection" mechanisms regulate the variance in cell phenotypes. Variance in cell phenotypes may arise from developmental-error or other stochastic processes, or be generated as is true of the immune system, as part of a developmental strategy. The model shows that stability-selection mechanisms may exert the stronger effect on overall organ or body performance. Selection based upon reliable inter-cellular signalling of phenotypic properties may be the key way that bodies anticipate and then constrain variance in cell phenotypes around the optimal cellular attributes, and suggests an advantage of developmentally-selected systems over instructional ones. High levels of investments in stability mechanisms also ensure homogeneous collections of cells that can translate "upwards" into developmentally stable organ systems and phenotypes. Environmental and genetic factors, as well as the prevalent mode of selection, may all affect developmental stability and thereby give rise to varying of somatic selection.

Animals↗
PubMed1998

Prion's progress: patterns and rates of molecular evolution in relation to spongiform disease.

Modification of the cellular prion protein has been correlated with the acquisition of several neurodegenerative diseases, including kuru, scrapie, bovine spongiform encephalopathy (BSE), and Creutzfeldt-Jakob disease (CJD). Sequence conservation and amino acid identity are known to influence the efficacy of interspecific transmission. We analyzed patterns of interspecific genetic variation with a view toward identifying features related to disease transmission. The reconstructed gene trees and amino acid tree were compared with the species tree, and all discordances observed were related to the species barrier of disease transmission. The rates of synonymous substitution, nonsynonymous substitution, and nucleotide content were determined for the protein-coding gene. Substitutions implicated in each of the prion diseases were found to occur in regions of the protein that are least variable across all species-opposite to the pattern of variability expected from interaction with an infectious pathogen. Amino acid residues related to the species barrier form a single cluster associated with the first alpha-helical domain of the protein. Residues related to sporadic and hereditary human prion disease form two separate clusters, associated with the second and third alpha-helical domains. Taken together, these results are consistent with the view that prion diseases arise from accidents in protein folding, rather than infection with an undiscovered virus-like particle. We speculate that the differences in disease phenotype between transmissable and hereditary forms could result from interactions between different parts of the protein during propagation.

Animals↗
PubMed1998

Reaction of N-acetylglycyllysine methyl ester with 2-alkenals: an alternative model for covalent modification of proteins.

Among the various reactions of lipid peroxidation products with proteins, 2-alkenals have been shown to react extensively with the epsilon-amino group of lysine residues [Zídek et al. (1997) Chem. Res. Toxicol. 10, 702-710]. To obtain additional information about the kinetic and mechanistic aspects of this modification, a model peptide (N-acetylglycyllysine O-methyl ester) was reacted with 2-hexenal. The reaction products were characterized through a combination of NMR and MS techniques. The structural elucidation efforts have shown the formation of pyridinium salts through the reaction of two or more alkenals with one amino group. Kinetic data were obtained using a continuous infusion of the reaction mixture into an electrospray ionization mass spectrometer. A mechanism is proposed that offers an alternative model for the formation of stable protein cross-links. The reaction progresses through a Schiff base intermediate to form a dihydropyridine species which can be alternatively reduced to form various 3,4- or 2,5-substituted pyridinium species or react with another Schiff base to form a trialkyl-substituted pyridinium structure. The stoichiometry of this structure (aldehyde/amine) is 3:2, in contrast to the widely accepted 1:2. Therefore, it represents another possible cross-linking mechanism for bifunctional products of lipid peroxidation.

Aldehydes↗
PubMed1997

Why do animals repeat displays?

Both agonistic and sexual animal displays often involve more than one performance of some specific display action. Since repetition is energetically costly there must be good reasons why a signaller should carry out such repetitive actions, rather than simply displaying once. We briefly review three different 'reasons' which arise from three different receiver assessment rules: when assessment is based on the average magnitude of all display actions so far, the reason for the repetition is to improve the accuracy of the estimate (model A); when the assessment is based solely on the action of greatest magnitude so far, the repetition is to replace the signal with one of greater magnitude (model B); when the assessment is based on the cumulative sum of all display actions so far, the repetition is to augment that sum (model C). We discuss how to characterize each case from an understanding of its expected optimal behaviour as predicted by formal models. For model A the mean magnitude of display actions should stay constant and the contest duration should depend on relative qualities. In models B and C the encounter duration depends only on the weaker participant. In model B each display action is greater than the previous, but only a small number of steps are expected. In model C the magnitude of display actions can either escalate, stay constant, or even decrease. The displays of cichlid fish, the roaring contests of red deer, Cervus elaphusthe calling of Blanchard's cricket frogs, Acris crepitans blanchardiand the pheromonal exchanges of yeast gametes are used as illustrative examples.

Journal Article↗
PubMed1996

Selection by somatic signals: the advertisement of phenotypic state through costly intercellular signals.

We develop a model of intercellular signalling, to explore the possibility that the signals exchanged between cells within a body may be subject to many of the same evolutionary pressures as signals exchanged between individuals whose genetic interests conflict. Evolutionary signalling theory maintains that signals, to be reliable indicators of need, intention or quality must be more costly than would be required merely to transmit a message. Cost guarantees that poor quality individuals are less able to display the high magnitude signals produced by the higher quality individuals. Receivers have been favoured by natural selection to attend only to the costliest signals, and thereby acquire honest information from the signaller. Hence the extravagant, costly ornamentation found among males of many species, ensures that females can accurately choose among them on the basis of their qualities. However, because somatic cells are normally perfectly genetically related, and are often denied access to the germ line, there will be minimal genetic conflicts of interest. This appears to imply that reliable intercellular signals should be produced without the need for cost to ensure their reliability. Nevertheless, we show that whenever cells vary in their phenotypic qualities in ways relevant to the fitness of the body, and given that there exists a class of cell that remains "ignorant' of its phenotypic state, costly intercellular signalling will evolve as a form of quality control. Specifically, we show that given variation in the cell population, signal cost will aid the identification and removal of cells that over-represent their true phenotypic state, and which therefore could lower fitness. Cells that under-represent their state are simply outcompeted by other cells. The cells of a body employ signals in a variety of intercellular interactions, including the development of the nervous system, the formation of neuromuscular junctions, and during the establishment of the immune repetoire. In each of these cases, cells may employ costly signals to advertise their phenotypic quality to other cells, and we review the evidence in support of this hypothesis: in effect, the cells may possess a molecular counterpart to the peacock's tail.

Animals↗
PubMed1993

Seeking the evolutionary regression coefficient: an analysis of what comparative methods measure.

Two alternative classes of comparative statistical method differ in the way that the comparative data are used to test for an association between two quantitative traits. Directional comparative methods use reconstructions of the ancestral character states to calculate the changes between ancestral and descendant conditions along the branches of the phylogenetic tree. The set of changes in two or more traits is used to test for evidence of correlated evolution. Cross-sectional techniques do not estimate changes along the branches of the tree, but rather make comparisons across the tips of a phylogeny, or between pairs of extant taxa (or between their higher nodes). These methods, then, study the association between pairs of traits representing the contemporary endpoints of evolution. The best known of the cross-sectional techniques, the species regression, simply regresses the species values of one variable onto those of another. However, it is shown here analytically that directional and cross-sectional methods, despite making very different use of the data, estimate precisely the same evolutionary parameter: the association between the changes in two variables along the branches of the phylogenetic tree. Thus, comparative statistical techniques are able to recover the historical trends of evolution, that is, the ways in which evolution has proceeded along the branches of the phylogenetic tree, from analysis of the variation among the contemporary species of a phylogeny. This means that the choice between the two alternative traditions of comparative study cannot be based upon what the different methods purport to measure, but rather must be based upon the statistical properties of particular methods. In the light of this result, it is discussed here whether there are statistical reasons to prefer some methods over others.

Animals↗
PubMed1993

Honest signalling among gametes.

The gametes of many lower eukaryotic organisms emit pheromones that attract gametes of the opposite mating type or sex. Gametes move or grow in the direction of the highest pheromone concentration, suggesting that the strength of the pheromonal signal is used to infer proximity, or that the strongest signal is most likely to be notice. Here I offer a new explanation of pheromonal signalling and chemotaxis in gametes. I show that pheromonal signals can be interpreted as sexually selected traits that honestly advertise variation in quality among gametes, given that signals are costly to produce and that gametes compete; by 'quality' I refer to some aspect of a gamete's fitness. A gamete's preference for a mating partner, then, is predicted to vary with the quality of a prospective partner as inferred from the strength of its signal. This view can explain characteristics of the signalling and mate selection behaviours of gametes that are not predicted by models of mate choice based on proximity or 'passive attraction' to the strongest signal. These include repeated partner exchanges, escalated exchanges of mating pheromones, and rejection of gametes that signal at low levels.

Animals↗
PubMed1992

Variation across species in the size of the nuclear genome supports the junk-DNA explanation for the C-value paradox.

The amount of DNA in the nuclear genome (the DNA C-value) of eukaryotes varies at least 80,000-fold across species, and yet bears little or no relation to organismic complexity or to the number of protein-coding genes. This phenomenon is known as the C-value paradox. One explanation for the C-value paradox attributes the size of the nuclear genome to 'junk' (typically non-coding) genetic elements that accumulate until the costs to the organism of replicating excess DNA select against it. Across species, organisms that develop at a slower rate should tolerate more junk DNA. Alternatively, junk DNA may function as a nucleo-skeleton to maintain the volume of the nucleus at a size proportional to the volume of the cytoplasm in the cell. Across species, the DNA C-value is predicted to vary with the nuclear and cytoplasmic volumes of cells. Previous studies have not been able to distinguish between the skeletal-DNA and junk-DNA explanations for the C-value paradox. We report a study of DNA content in 24 salamander species which does. The size of the nuclear genome is correlated with developmental rate even after the effects of nuclear and cytoplasmic volume have been removed. However, genome size is not correlated with cytoplasmic volume after controlling for developmental rate. These results support the view that junk DNA accumulates in the nuclear genome until the costs of replicating it become too great, rather than that it functions as a nucleo-skeleton.

Animals↗
PubMed1987

Depressive thinking and depression: relations with personality and social resources.

The mechanisms by which social supports and personality variables may buffer against psychopathology are not well understood. We studied depression, depressive cognitions, social supports, and self-esteem in a sample of 68 spouse-caregivers of patients with Alzheimer's Disease in an attempt to identify possible buffering mechanisms of the latter two variables. Specifically, we hypothesized that the well-known relation of depressive cognitions to depression would vary as a function of satisfaction with social supports and with level of self-esteem. Hierarchical multiple regression analyses conducted to predict depression revealed significant and independent main effects for depressive cognitions (p less than .01), social supports (p less than .025), and self-esteem (p less than .001), with depressive cognitions associated with higher depression and the other two variables associated with reduced depression (R2 = .53 for the three main effects). In addition, the relation of depressive cognitions with depression varied substantially depending on the level of social supports (p less than .01); caregivers with high levels of depressive cognitions had high levels of depression only if social supports were low (R2 = .61 including interaction). Self-esteem and depressive cognitions showed a similar interaction, but it failed to reach significance. Analyses to determine whether self-esteem and social supports were directly associated with lower depressive cognitive activity yielded a main effect for self-esteem only (p less than .03). Thus, whereas social supports and self-esteem were directly associated with lower depression, only the social supports variable was further associated with reduced depression because it apparently buffered the impact of depressive thinking. Self-esteem was also indirectly associated with lower depression via its relation with lower depressive thinking. Implications of our results for cognitive theories of depression and for the psychosocial mechanisms of stress buffering are discussed.

Adult↗
PubMed1984

Prediction of pregnancy complications: an application of the biopsychosocial model.

This paper describes a pilot study of biomedical and psychosocial risk and the outcome of pregnancy. Ninety-three pregnant women completed four instruments to identify three types of psychosocial risk: life events, family function and social support. Biomedical risk was identified through analysis of self-reported health histories and hospital records. Information on complications of pregnancy was obtained from hospital delivery records. Further complications data were obtained by a home interview at 6 weeks postpartum. In the sample studied, from an agricultural-university community in Eastern Washington, biomedical risk alone was not substantially related to complications. Psychosocial risk was related to both delivery and postpartum complications. Family function was the best single psychosocial predictor. The interaction between family function and biomedical risk also predicted complications reliability. A total of 11% of variance in postpartum complications could be explained jointly by biomedical and psychosocial risk. The results of the study suggest that psychosocial risk assessment alone and in interaction with biomedical risk assessment will offer significant improvement in the identification of women who may experience pregnancy complication.

Adult↗
PubMed1983

Inability of dimethyl sulfoxide and 5-fluorouracil to open the blood-brain barrier.

The inability of most chemotherapeutic agents to adequately penetrate the blood-brain barrier (BBB), in either normal brain or tumor-infiltrated brain, is a major factor limiting the use of chemotherapy in central nervous system malignancy. This barrier, however, can be opened in a reversible manner by the intra-arterial administration of hyperosmotic agents such as mannitol. It has been suggested that the intravenous administration of dimethyl sulfoxide (DMSO) or 5-fluorouracil (5-FU) can accomplish the same thing in a less invasive manner. We have not been able to confirm these findings. DMSO was administered to 25 rats intravenously at concentrations ranging from 25 to 90% or into the internal carotid artery at a concentration of 30%. The penetration of methotrexate, Evans blue-albumin, and hexosaminidase A was then evaluated at intervals ranging from 1.5 to 3.5 hours after administration. Significant barrier opening was not observed in animals receiving intravenous DMSO. Barrier modification, albeit generally modest, was obtained in animals receiving intracarotid DMSO, but this may have been the result of grand mal seizures, inasmuch as 5 of 6 of these animals had such seizures. Several of the animals receiving i.v. DMSO also had seizures, and all animals developed varying degrees of hematuria. Similarly, 5-FU was administered at a dose of 30 mg/kg i.v. and the permeability of the BBB to either Evans blue-albumin or methotrexate was evaluated. No increased permeability of the BBB to these two markers was observed. In summary, osmotic BBB opening in our hands remains the most consistent and reliable means available to open the BBB in a reversible fashion. Neither intravenous DMSO nor 5-FU seems to increase the delivery of chemotherapy or protein tracer to the central nervous system, and the use of DMSO can result in seizures and hematuria.

Animals↗