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At least 937 records · Page 52Linked to original sources
PubMed2003

Sex-specific associative learning cues and inclusive fitness benefits in the Seychelles warbler.

In cooperative breeding vertebrates, indirect fitness benefits would be maximized by subordinates that accurately assess their relatedness to group offspring and preferentially help more closely related kin. In the Seychelles warbler (Acrocephalus sechellensis), we found a positive relationship between subordinate-nestling kinship (determined using microsatellite marker genotypes) and provisioning rates, but only for female subordinates. Female subordinates that helped were significantly more related to the nestlings than were nonhelpers, and the decision to help appears to be based on associative learning cues. High levels of female infidelity means that subordinates cannot trust their legitimacy through the male line, consequently they appear to use the continued presence of the primary female, but not the primary male, as a reliable cue to determine when to feed nestlings. By using effective discrimination, female subordinates are able to maximize the indirect benefits gained within a cooperative breeding system otherwise driven primarily by direct breeding benefits.

Animals↗
PubMed1993

Evolutionary games and computer simulations.

The Prisoner's Dilemma has long been considered the paradigm for studying the emergence of cooperation among selfish individuals. Because of its importance, it has been studied through computer experiments as well as in the laboratory and by analytical means. However, there are important differences between the way a system composed of many interacting elements is simulated by a digital machine and the manner in which it behaves when studied in real experiments. In some instances, these disparities can be marked enough so as to cast doubt on the implications of cellular automata-type simulations for the study of cooperation in social systems. In particular, if such a simulation imposes space-time granularity, then its ability to describe the real world may be compromised. Indeed, we show that the results of digital simulations regarding territoriality and cooperation differ greatly when time is discrete as opposed to continuous.

Animals↗
PubMed1997

Applying experimental data to protein fold prediction with the genetic algorithm.

Specific residue interactions as revealed from a few and readily available experiments can be quite important in shaping a protein's tertiary topology by complementing basic and general folding principles. This experimental information is employed in structure prediction (mainchain topology) based on sequence knowledge and the genetic algorithm with its ability to optimize simultaneously many parameters. Examples investigated include the distribution of cysteinyl S-S bonds, protein side-chain ligands to iron-sulfur cages, cofactor-ligands, crosslinks amongst side-chains, and conserved hydrophobic and catalytic residues. Such interactions yield an improvement in the predicted topology (0.4-6.6 A root mean square deviation in the positions of the backbone C alpha-atoms relative to those observed) compared with those resulting from simulations relying only on basic protein folding principles. For several examples the resultant topology depended critically on knowledge of the few and specific interactions such that the relationship between predicted and observed C alpha-positions was near random without their use. The combined methodology (experimental data and the genetic algorithm) should prove helpful in settings where experiment and theory can cooperate in successive steps to elucidate an unknown structure.

Algorithms↗
PubMed2004

The role of pharmacoepidemiology and pharmacoeconomics in promoting access and stimulating innovation.

Answering the demanding questions asked of pharmacotherapy in the 21st century will require more reliance on the disciplines of pharmacoepidemiology and pharmacoeconomics. Pharmacoepidemiology can help assess patterns and appropriateness of drug utilisation, provide explanations for poor compliance, quantify the frequency and severity of side effects, and aid in the design and evaluation of interventions to improve drug use and outcomes. Pharmacoeconomics can help determine whether a new costlier product offers sufficient clinical advantage over its predecessors to justify the increased cost. Taken together, pharmacoepidemiology and pharmacoeconomics represent the next logical step in the evolution of medication assessment; their judicious deployment can help ensure both access to new medicines and innovation.

Cooperative Behavior↗
PubMed2005

Directed evolution of a ring-cleaving dioxygenase for polychlorinated biphenyl degradation.

DoxG, an extradiol dioxygenase involved in the aerobic catabolism of naphthalene, possesses a weak ability to cleave 3,4-dihydroxybiphenyls (3,4-DHB), critical polychlorinated biphenyl metabolites. A directed evolution strategy combining error-prone PCR, saturation mutagenesis, and DNA shuffling was used to improve the polychlorinated biphenyl-degrading potential of DoxG. Screening was facilitated through analysis of filtered, digital imaging of plated colonies. A simple scheme, which is readily adaptable to other activities, enabled the screening of >10(5) colonies/h. The best variant, designated DoxGSMA2, cleaved 3,4-DHB with an apparent specificity constant of 2.0 +/- 0.3 x 10(6) m(-1) s(-1), which is 770 times that of wild-type (WT) DoxG. The specificities of DoxGSMA2 for 1,2-DHN and 2,3-DHB were increased by 6.7-fold and reduced by 2-fold, respectively, compared with the WT enzyme. DoxGSMA2 contained three substituted residues with respect to the WT enzyme: L190M, S191W, and L242S. Structural data indicate that the side chains of residues 190 and 242 occur on opposite walls of the substrate binding pocket and may interact directly with the distal ring of 3,4-DHB or influence contacts between this substrate and other residues. Thus, the introduction of two bulkier residues on one side of the substrate binding pocket and a smaller residue on the other may reshape the binding pocket and alter the catalytically relevant interactions of 3,4-DHB with the enzyme and dioxygen. Kinetic analyses reveal that the substitutions are anti-cooperative.

Base Sequence↗
PubMed1994

Structure-function relationships in the neurotrophin family.

The study of structure-function relationships in the neurotrophin family has in recent years increased our understanding of several important aspects of neurotrophin function. Site-directed mutagenesis studies have localized amino acid residues important for binding to the low-affinity (p75LNGFR), as well as to the members of the Trk family of tyrosine kinase receptors. A cluster of positively charged residues has been shown to form a surface for binding to p75LNGFR in all four neurotrophins. Differences in the spatial distribution of these charges among the different neurotrophins may explain some of their distinct binding properties. Elimination of these positive charges drastically reduces binding to p75LNGFR but not to the Trk family members, and it does not impair the biological properties of the neurotrophins in vitro, arguing that binding to and activation of Trk receptors is sufficient to mediate the biological responses of neurotrophins. In contrast, the binding sites to Trk receptors appear to be formed by discontinuous stretches of amino acid residues distributed throughout the primary sequence of the molecule. These include the N-terminus, some of the variable loop regions and a beta-strand. Despite their apparent distribution, when viewed in the three-dimensional structure of NGF, these residues appear grouped on one side of the neurotrophin dimer, delineating a continuous surface extending approximately parallel to the twofold symmetry axis of the molecule. Two symmetrical surfaces are formed along the axis of the neurotrophin dimer providing a model for ligand-mediated receptor dimerization. In the neurotrophin family, co-evolution of cognate ligands and Trk receptors has developed specific contacts through different residues in the same variable regions of the neurotrophins. Thus, binding specificity is determined by the cooperation of distinct active and inhibitory binding determinants that restrict ligand-receptor interactions. Binding determinants to the Trk receptors can be manipulated independently in a rational fashion to create neurotrophin analogues with novel ligand-binding properties. In this way, second-generation chimeric neurotrophins with multiple specificities (pan-neurotrophins) have been engineered which may have valuable applications in the treatment of neurodegeneration and nerve damage.

Amino Acid Sequence↗
PubMed2004

Data-based model and parameter evaluation in dynamic transcriptional regulatory networks.

Finding the causality and strength of connectivity in transcriptional regulatory networks from time-series data will provide a powerful tool for the analysis of cellular states. Presented here is the design of tools for the evaluation of the network's model structure and parameters. The most effective tools are found to be based on evolution strategies. We evaluate models of increasing complexity, from lumped, algebraic phenomenological models to Hill functions and thermodynamically derived functions. These last functions provide the free energies of binding of transcription factors to their operators, as well as cooperativity energies. Optimization results based on published experimental data from a synthetic network in Escherichia coli are presented. The free energies of binding and cooperativity found by our tools are in the same physiological ranges as those experimentally derived in the bacteriophage lambda system. We also use time-series data from high-density oligonucleotide microarrays of yeast meiotic expression patterns. The algorithm appropriately finds the parameters of pairs of regulated regulatory yeast genes, showing that for related genes an overall reasonable computation effort is sufficient to find the strength and causality of the connectivity of large numbers of them.

Algorithms↗
PubMed2005

Fibrinogen and fibronectin binding cooperate for valve infection and invasion in Staphylococcus aureus experimental endocarditis.

The expression of Staphylococcus aureus adhesins in Lactococcus lactis identified clumping factor A (ClfA) and fibronectin-binding protein A (FnBPA) as critical for valve colonization in rats with experimental endocarditis. This study further analyzed their role in disease evolution. Infected animals were followed for 3 d. ClfA-positive lactococci successfully colonized damaged valves, but were spontaneously eradicated over 48 h. In contrast, FnBPA-positive lactococci progressively increased bacterial titers in vegetations and spleens. At imaging, ClfA-positive lactococci were restricted to the vegetations, whereas FnBPA-positive lactococci also invaded the adjacent endothelium. This reflected the capacity of FnBPA to trigger cell internalization in vitro. Because FnBPA carries both fibrinogen- and fibronectin-binding domains, we tested the role of these functionalities by deleting the fibrinogen-binding domain of FnBPA and supplementing it with the fibrinogen-binding domain of ClfA in cis or in trans. Deletion of the fibrinogen-binding domain of FnBPA did not alter fibronectin binding and cell internalization in vitro. However, it totally abrogated valve infectivity in vivo. This ability was restored in cis by inserting the fibrinogen-binding domain of ClfA into truncated FnBPA, and in trans by coexpressing full-length ClfA and truncated FnBPA on two separate plasmids. Thus, fibrinogen and fibronectin binding could cooperate for S. aureus valve colonization and endothelial invasion in vivo.

Adhesins, Bacterial↗
PubMed2001

An evolutionary-game model of tumour-cell interactions: possible relevance to gene therapy.

Evolutionary games have been applied as simple mathematical models of populations where interactions between individuals control the dynamics. Recently, it has been proposed to use this type of model to describe the evolution of tumour cell populations with interactions between cells. We extent the analysis to allow for synergistic effects between cells. A mathematical model of a tumour cell population is presented in which population-level synergy is assumed to originate through the interaction of triplets of cells. A threshold of two cooperating cells is assumed to be required to produce a proliferative advantage. The mathematical behaviour of this model is explored. Even this simple synergism (minor clustering effect) is sufficient to generate qualitatively different cell-population dynamics from the models published previously. The most notable feature of the model is the existence of an unstable internal equilibrium separating two stable equilibria. Thus, cells of a malignant phenotype can exist in a stable polymorphism, but may be driven to extinction by relatively modest perturbations of their relative frequency. The proposed model has some features that may be of interest to biological interpretations of gene therapy. Two prototypical strategies for gene therapy are suggested, both of them leading to extinction of the malignant phenotype: one approach would be to reduce the relative proportion of the cooperating malignant cell type below a certain critical value. Another approach would be to increase the critical threshold value without reducing the relative frequency of cells of the malignant phenotype.

Algorithms↗
PubMed1988

Physicians and the organizational evolution of medicine.

Within medicine there is growing uneasiness and debate about changes in medical care delivery. Much of this concern centers on the evolution of organizations and the role of physicians. The emergence of multi-institutional organizations, the rise of investor-owned health care corporations, and the expansion of group medical practice illustrate the increasing organizational influence in medicine. Added to these trends are new financial incentives confronting both physicians and organizations so that the environment increasingly favors conflict. This article reviews the primary strategies for resolving physician-organization conflicts, including cooperation between physicians and organizations, having physician representatives in governance and management, restructuring incentives, and restructuring organizations. Although these strategies have various merits, we suggest that every physician has a personal responsibility to become more involved in organization and management issues. Physicians can play an important role in guiding the evolution of medicine.

Conflict, Psychological↗
PubMed2001

Complete mitochondrial genome sequences of two extinct moas clarify ratite evolution.

The origin of the ratites, large flightless birds from the Southern Hemisphere, along with their flighted sister taxa, the South American tinamous, is central to understanding the role of plate tectonics in the distributions of modern birds and mammals. Defining the dates of ratite divergences is also critical for determining the age of modern avian orders. To resolve the ratite phylogeny and provide biogeographical data to examine these issues, we have here determined the first complete mitochondrial genome sequences of any extinct taxa--two New Zealand moa genera--along with a 1,000-base-pair sequence from an extinct Madagascan elephant-bird. For comparative data, we also generated 12 kilobases of contiguous sequence from the kiwi, cassowary, emu and two tinamou genera. This large dataset allows statistically precise estimates of molecular divergence dates and these support a Late Cretaceous vicariant speciation of ratite taxa, followed by the subsequent dispersal of the kiwi to New Zealand. This first molecular view of the break-up of Gondwana provides a new temporal framework for speciation events within other Gondwanan biota and can be used to evaluate competing biogeographical hypotheses.

Animals↗
PubMed2000

Maximal indirect development, set-aside cells, and levels of selection.

The evolution of metazoan development as described by Davidson et al. (1995. Science 270:1319-1325) is readily interpretable in terms of levels-of-selection conflicts, for instance, as recently modeled by Michod (1999. Darwinian Dynamics, Princeton, NJ: Princeton University Press). Davidson et al. propose certain features of early bilaterians including small size, a small and fixed number of cell divisions during and subsequent to cleavage, and specification of cell fates prior to cell movement. These features suggest constraints on certain parameters of Michod's model, specifically t (the time available for cell division) and b (the benefit to cells of not cooperating in terms of their rate of replication). Such constraints clearly enhance between-cell cooperation and allow multicellularity to more easily evolve and be maintained. Nevertheless, these constraints are completely abrogated by the phenomenon of "set-aside cells," that is, undifferentiated cells that retain indefinite division potential. Levels-of-selection theory predicts that the evolution of these set-aside cells must be accompanied by features which alleviate cell-cell competition, and indeed the results of Ransick et al. (1996. Proc Natl Acad Sci USA 93:6759-6763) support this prediction: the evolution of "set-aside cells" in metazoans was accompanied by the evolution of the sequestration of the germ line.

Animals↗
PubMed2005

Cooperation, social networks, and the emergence of leadership in a prisoner's dilemma with adaptive local interactions.

Cooperative behavior among a group of agents is studied assuming adaptive interactions. Each agent plays a Prisoner's Dilemma game with its local neighbors, collects an aggregate payoff, and imitates the strategy of its best neighbor. Agents may punish or reward their neighbors by removing or sustaining the interactions, according to their satisfaction level and strategy played. An agent may dismiss an interaction, and the corresponding neighbor is replaced by another randomly chosen agent, introducing diversity and evolution to the network structure. We perform an extensive numerical and analytical study, extending results in M. G. Zimmermann, V. M. Eguíluz, and M. San Miguel, Phys. Rev. E 69, 065102(R) (2004). We show that the system typically reaches either a full-defective state or a highly cooperative steady state. The latter equilibrium solution is composed mostly by cooperative agents, with a minor population of defectors that exploit the cooperators. It is shown how the network adaptation dynamics favors the emergence of cooperators with the highest payoff. These "leaders" are shown to sustain the global cooperative steady state. Also we find that the average payoff of defectors is larger than the average payoff of cooperators. Whenever "leaders" are perturbed (e.g., by addition of noise), an unstable situation arises and global cascades with oscillations between the nearly full defection network and the fully cooperative outcome are observed.

Journal Article↗
PubMed1999

Systematic relationships within the dasyurid marsupial tribe Sminthopsini--a multigene approach.

We report analyses of complete DNA sequences of the mitochondrial cytochrome b (1146 bp), 12S rRNA (974 bp), partial control region (371 bp) loci, and the nuclear protamine P1 (616 bp) gene from all but one species (Sminthopsis butleri) of the dasyurid marsupial tribe Sminthopsini, as well as several outgroups. Parsimony analyses of combined nuclear and mitochondrial data suggest that Antechinomys is sister to a clade consisting of Sminthopsis and Ningaui. Parsimony, maximum-likelihood, and mixed-model distance analyses consistently resolve several species groups within Sminthopsis. The Macroura group includes S. macroura, S. virginiae, S. douglasi, and S. bindi; S. butleri is also included here on the basis of partial 12S rRNA sequences. S. crassicaudata is resolved as sister to the Macroura clade. The Murina group includes S. murina, S. leucopus, S. gilberti, S. dolichura, and S. archeri. S. griseoventer and S. aitkeni are resolved as a clade, and there is moderate support for a group consisting of the genetically divergent species S. psammophila, S. hirtipes, S. youngsoni, and S. ooldea (possibly along with S. longicaudata and S. granulipes). Compositions of species groups are partially congruent with clades previously proposed on the basis of morphological data. Radiations within Sminthopsini appear to be coincident with major environmental changes since the mid-Miocene.

Animals↗
PubMed1995

Binding of adenine and adenine-related compounds to the clay montmorillonite and the mineral hydroxylapatite.

The first living things may have consisted of no more than RNA or RNA-like molecules bound to the surfaces of mineral particles. A key aspect of this theory is that these mineral particles have binding sites for RNA and its prebiotic precursors. The object of this study is to explore the binding properties of two of the best studied minerals, montmorillonite and hydroxylapatite, for possible precursors of RNA. The list of compounds investigated includes purines, pyrimidines, nucleosides, nucleotides, nucleotide coenzymes, diaminomaleonitrile and aminoimidazole carboxamide. Affinities for hydroxylapatite are dominated by ionic interactions between negatively charged small molecules and positively charged sites in the mineral. Binding to montmorillonite presents a more complex picture. These clay particles have a high affinity for organic ring structures which is augmented if they are positively charged. This binding probably takes place on the negatively charged faces of these sheet-like clay particles. Additional binding sites on the edges of these sheets have a moderate affinity for negatively charged molecules. Small molecules that bind to these minerals sometimes bind independently to sites on the minerals and sometimes bind cooperatively with favorable interactions between the bound molecules.

Adenine↗
PubMed1979

The reversal immune surveillance hypothesis.

The proposed reveral immune surveillance hypothesis is based on the identification primarily of self and secondarily of foreignness, unlike the original hypothesis that is based on the identification of foreignness per se. The proposed system is considered to have evolved from the invertebrates through to the vertebrates to become more complex in the mammals, and involves the identification of cell types by lymphocytes through the cell type surface pattern and major histocompatibility antigens. The identification of self and associated foreignness by the immune system is required for the regulation of cell differentiation and replication, and because of this design, the ability of the immune system to destroy foreignness can be regarded as a natural consequence. The reversal immune surveillance hypothesis explains why spontaneously occurring tumours may not be antigenic, in the sense of eliciting their own destruction, and is consistent with the destruction of tumour cells that display significant amounts of viral antigens or gross antigenic changes induced by carcinogenic agents. It is also able to explain the stimulation and inhibition of tumour development.

Animals↗
PubMed1989

The detection in human sera of antisperm antibodies reactive with FA-1, an evolutionarily conserved antigen, and with murine spermatozoa.

Evolutionarily conserved antigens are present on spermatozoa of several mammalian species. We tested sera from infertile men and women containing antisperm antibodies (ASAs) for their reactivity with FA-1, an antigen known to be present on murine and human spermatozoa. Fifty percent of male sera and 63% of female sera contained anti-FA-1 antibodies, as judged by enzyme linked immunosorbent assay (ELISA). Fourteen percent of male sera and 50% of female sera were also shown to possess ASAs reactive with living mouse spermatozoa, and murine in vitro fertilization was inhibited by human antibodies. These results suggest that the transfer of immunoglobulins from human sera to spermatozoa of other species may provide a model to study how ASAs effect sperm function.

Absorption↗