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D S Wilson

Publications and source records attributed to D S Wilson.

At least 19 recordsLinked to original sources

Replica Ornstein-Zernike self-consistent theory for mixtures in random pores.

We present a self-consistent integral equation theory for a binary liquid in equilibrium with a disordered medium, based on the formalism of the replica Ornstein-Zernike (ROZ) equations. Specifically, we derive direct formulas for the chemical potentials and the zero-separation theorems (the latter provide a connection between the chemical potentials and the fluid cavity distribution functions). Next we solve a modified-Verlet closure to ROZ equations, which has built-in parameters that can be adjusted to satisfy the zero-separation theorems. The degree of thermodynamic consistency of the theory is also kept under control. We model the binary fluid in random pores as a symmetrical binary mixture of nonadditive hard spheres in a disordered hard-sphere matrix and consider two different values of the nonadditivity parameter and of the quenched matrix packing fraction, at different mixture concentrations. We compare the theoretical structural properties as obtained through the present approach with Percus-Yevick and Martinov-Sarkisov integral equation theories, and assess both structural and thermodynamic properties by performing canonical standard and biased grand canonical Monte Carlo simulations. Our theory appears superior to the other integral equation schemes here examined and provides reliable estimates of the chemical potentials. This feature should be useful in studying the fluid phase behavior of model adsorbates in random pores in general.

Journal Article↗

The use of mRNA display to select high-affinity protein-binding peptides.

We report the use of "mRNA display," an in vitro selection technique, to identify peptide aptamers to a protein target. mRNA display allows for the preparation of polypeptide libraries with far greater complexity than is possible with phage display. Starting with a library of approximately 10(13) random peptides, 20 different aptamers to streptavidin were obtained, with dissociation constants as low as 5 nM. These aptamers function without the aid of disulfide bridges or engineered scaffolds, yet possess affinities comparable to those for monoclonal antibody-antigen complexes. The aptamers bind streptavidin with three to four orders of magnitude higher affinity than those isolated previously by phage display from lower complexity libraries of shorter random peptides. Like previously isolated peptides, they contain an HPQ consensus motif. This study shows that, given sufficient length and diversity, high-affinity aptamers can be obtained even from random nonconstrained peptide libraries. By engineering structural constraints into these ultrahigh complexity peptide libraries, it may be possible to produce binding agents with subnanomolar binding constants.

Amino Acid Sequence↗

One-step purification of recombinant proteins using a nanomolar-affinity streptavidin-binding peptide, the SBP-Tag.

We describe the use of the SBP-tag, a new streptavidin-binding peptide, for both the one-step purification and the detection of recombinant proteins. The SBP-tag sequence is 38 amino acids long and binds to streptavidin with an equilibrium dissociation constant of 2.5 nM. We demonstrate that a single-step purification of SBP-tagged proteins from bacterial extract yields samples that are more pure than those purified using maltose-binding protein or the His-tag. The capacity of the immobilized streptavidin used to purify SBP-tagged proteins is about 0.5 mg per milliliter of matrix, which is high enough to isolate large quantities of proteins for further study. Also, the elution conditions from the streptavidin column are very mild and specific, consisting of the wash buffer plus biotin. This combination of high-affinity, high-yield, mild elution conditions, and simplicity of use makes the SBP-tag suitable for high-throughput protein expression/purification procedures, including robotically manipulated protocols with microtiter plates. Additionally, the SBP-tag can be used for detection since a wide variety of streptavidin-conjugated fluorescent and enzymatic systems are commercially available. We also present a new, rapid, method for the measurement of protein-protein, protein-peptide, or protein-small molecule equilibrium dissociation constants that require as little as 1 fmol of labeled protein. We call this method the spin-filter binding inhibition assay.

Affinity Labels↗

Religious groups as adaptive units.

This essay provides a sketch of religion as a set of biologically and culturally evolved adaptations that enable human groups to function as adaptive units. Recent developments in evolutionary biology make such a group-level interpretation of religion more plausible than in the past. A brief survey of relevant concepts is followed by a relatively detailed interpretation of Calvinism as a religious system in which explicit behavioral prescriptions, beliefs about God and his relationship with people, and numerous social control mechanisms combined to change the city of Geneva from a collection of warring factions to a unified population.

Cultural Evolution↗

Artificial ecosystem selection.

Artificial selection has been practiced for centuries to shape the properties of individual organisms, providing Darwin with a powerful argument for his theory of natural selection. We show that the properties of whole ecosystems can also be shaped by artificial selection procedures. Ecosystems initiated in the laboratory vary phenotypically and a proportion of the variation is heritable, despite the fact that the ecosystems initially are composed of thousands of species and millions of individuals. Artificial ecosystem selection can be used for practical purposes, illustrates an important role for complex interactions in evolution, and challenges a widespread belief that selection is most effective at lower levels of the biological hierarchy.

Biological Evolution↗

Population viscosity and the evolution of altruism.

The term population viscosity refers to limited dispersal, which increases the genetic relatedness of neighbors. This effect both supports the evolution of altruism by focusing the altruists' gifts on relatives of the altruist, and also limits the extent to which altruism may emerge by exposing clusters of altruists to stiffer local competition. Previous analyses have emphasized the way in which these two effects can cancel, limiting the viability of altruism. These papers were based on models in which total population density was held fixed. We present here a class of models in which population density is permitted to fluctuate, so that patches of altruists are supported at a higher density than patches of non-altruists. Under these conditions, population viscosity can support the selection of both weak and strong altruism.

Altruism↗

Constructing high complexity synthetic libraries of long ORFs using in vitro selection.

We present a method that can significantly increase the complexity of protein libraries used for in vitro or in vivo protein selection experiments. Protein libraries are often encoded by chemically synthesized DNA, in which part of the open reading frame is randomized. There are, however, major obstacles associated with the chemical synthesis of long open reading frames, especially those containing random segments. Insertions and deletions that occur during chemical synthesis cause frameshifts, and stop codons in the random region will cause premature termination. These problems can together greatly reduce the number of full-length synthetic genes in the library. We describe a strategy in which smaller segments of the synthetic open reading frame are selected in vitro using mRNA display for the absence of frameshifts and stop codons. These smaller segments are then ligated together to form combinatorial libraries of long uninterrupted open reading frames. This process can increase the number of full-length open reading frames in libraries by up to two orders of magnitude, resulting in protein libraries with complexities of greater than 10(13). We have used this methodology to generate three types of displayed protein library: a completely random sequence library, a library of concatemerized oligopeptide cassettes with a propensity for forming amphipathic alpha-helical or beta-strand structures, and a library based on one of the most common enzymatic scaffolds, the alpha/beta (TIM) barrel.

Amino Acid Sequence↗

Artificial selection of microbial ecosystems for 3-chloroaniline biodegradation.

We present a method for selecting entire microbial ecosystems for bioremediation and other practical purposes. A population of ecosystems is established in the laboratory, each ecosystem is measured for a desired property (in our case, degradation of the environmental pollutant 3-chloroaniline), and the best ecosystems are used as 'parents' to inoculate a new generation of 'offspring' ecosystems. Over many generations of variation and selection, the ecosystems become increasingly well adapted to produce the desired property. The procedure is similar to standard artificial selection experiments except that whole ecosystems, rather than single individuals, are the units of selection. The procedure can also be understood in terms of complex system theory as a way of searching a vast combinatorial space (many thousands of microbial species and many thousands of genes within species) for combinations that are especially good at producing the desired property. Ecosystem-level selection can be performed without any specific knowledge of the species that comprise the ecosystems and can select ensembles of species that would be difficult to discover with more reductionistic methods. Once a 'designer ecosystem' has been created by ecosystem-level selection, reductionistic methods can be used to identify the component species and to discover how they interact to produce the desired effect.

Aniline Compounds↗

In vitro selection of functional nucleic acids.

In vitro selection allows rare functional RNA or DNA molecules to be isolated from pools of over 10(15) different sequences. This approach has been used to identify RNA and DNA ligands for numerous small molecules, and recent three-dimensional structure solutions have revealed the basis for ligand recognition in several cases. By selecting high-affinity and -specificity nucleic acid ligands for proteins, promising new therapeutic and diagnostic reagents have been identified. Selection experiments have also been carried out to identify ribozymes that catalyze a variety of chemical transformations, including RNA cleavage, ligation, and synthesis, as well as alkylation and acyl-transfer reactions and N-glycosidic and peptide bond formation. The existence of such RNA enzymes supports the notion that ribozymes could have directed a primitive metabolism before the evolution of protein synthesis. New in vitro protein selection techniques should allow for a direct comparison of the frequency of ligand binding and catalytic structures in pools of random sequence polynucleotides versus polypeptides.

Nucleic Acids↗

Kinetics of selenium incorporation into tissues of female mallard ducks.

Selenium is essential for both mammalian and avian species, although its metabolism in birds has been less thoroughly studied. Little information has been available on the kinetics of selenium in birds, especially as it relates to the teratogenicity seen in waterfowl consuming excessive amounts. This study describes the pharmacokinetics of small amounts of 75Se as selenious acid injected into female mallard ducks. Labeled selenium was injected into a wing vein of restrained animals and tissues taken at five different time points up to 24 h post-injection. Selenium levels as percent of injected dose were determined in liver, kidney, heart, lung, adrenals, thyroid, spleen, pancreas, ovaries, intestine, muscle and plasma. Estimates of kinetic parameters (uptake and elimination rates, time of maximum concentration and maximum concentration) were obtained with a non-linear kinetics computer program (PCNONLIN, SCI Software, Lexington, KY). Results showed four basic patterns of distribution, uptake and elimination. Visceral tissues exhibited a triphasic pattern with a rapid rise, a decline followed by a distinctive increase in levels between the last two time points. Brain uptake was continuous over the 24 h. Plasma rose rapidly and then declined to a constant level. The ovaries as a tissue of interest relating to the teratogenic effects of selenium showed the greatest relative increase at 24 h, suggesting kinetic mechanisms consistent with a pathway that might lead to accumulation of toxic levels and teratogenic effects during embryo development.

Animals↗

Direct regulation of rhodopsin 1 by Pax-6/eyeless in Drosophila: evidence for a conserved function in photoreceptors.

Pax-6 is a transcription factor containing both a homeodomain (HD) and a Paired domain (PD). It functions as an essential regulator of eye development in both Drosophila and vertebrates, suggesting an evolutionarily conserved origin for different types of metazoan eyes. Classical morphological and phylogenetic studies, however, have concluded that metazoan eyes have evolved many times independently. These apparently contradictory findings may be reconciled if the evolutionarily ancient role of Pax-6 was to regulate structural genes (e.g., rhodopsin) in primitive photoreceptors, and only later did it expand its function to regulate the morphogenesis of divergent and complex eye structures. In support of this, we present evidence that eyeless (ey), which encodes the Drosophila homolog of Pax-6, directly regulates rhodopsin 1 (rh1) expression in the photoreceptor cells. We detect ey expression in both larval and adult terminally differentiated photoreceptor cells. We show that the HD of Ey binds to a palindromic HD binding site P3/RCS1 in the rh1 promoter, which is essential for rh1 expression. We further demonstrate that, in vivo, P3/RCS1 can be replaced by binding sites specific for the PD of Ey. P3/RCS1 is conserved in the promoters of all Drosophila rhodopsin genes as well as in many opsin genes in vertebrates. Mutimerized P3 sites in front of a basal promoter are able to drive the expression of a reporter gene in all photoreceptors. These results suggest that Pax-6/Ey directly regulates rhodopsin 1 gene expression by binding to the conserved P3/RCS1 element in the promoter.

Animals↗

Conservation and diversification in homeodomain-DNA interactions: a comparative genetic analysis.

Nearly all metazoan homeodomains (HDs) possess DNA binding targets that are related by the presence of a TAAT sequence. We use an in vitro genetic DNA binding site selection assay to refine our understanding of the amino acid determinants for the recognition of the TAAT site. Superimposed upon the conserved ability of metazoan HDs to recognize a TAAT core is a difference in their preference for the bases that lie immediately 3' to it. Amino acid position 50 of the HD has been shown to discriminate among these base pairs, and structural studies have suggested that water-mediated hydrogen bonds and van der Waals contacts underlie for this ability. Here, we show that each of six amino acids tested at position 50 can confer a distinct DNA binding specificity.

Amino Acid Sequence↗

CD18 antibody treatment limits early myocardial reperfusion injury after initial leukocyte deposition.

Following myocardial ischemia, initial reperfusion with whole blood impairs the recovery of ventricular function. The exact mechanisms underlying early myocardial reperfusion injury are not clear, but leukocytes play an important role. In this study, we tested if treating the initial blood reperfusate with a monoclonal antibody (CL26) against the leukocyte adhesion protein (CD18 would reduce the leukocyte contribution to early reperfusion injury. We reasoned that blocking CD18 would reduce the initial retention of leukocytes in the heart and thereby limit the inflammatory response. Rat hearts were isolated and perfused at constant flow with a red cell-rich solution (K2RBC). The perfusate was not recirculated. Baseline measures were made of coronary flow, perfusion pressure, and ventricular pump function. No-flow, normothermic ischemia was induced for 30 min, followed immediately by reperfusion, at the preischemic flowrate, with diluted whole blood (DWB, treated with either vehicle or CL26). Reperfusion was continued with K2RBC for 40 min more, during which postischemic measures were made. We found that the cardiac retention of leukocytes was not significantly different for the two groups, nor were the recoveries of ventricular function. Later in reperfusion (R35), the coronary blood flowrate and the coronary vascular resistances were not different; however, the recoveries of ventricular pump function were significantly different (+dP/dt @ R35 (%Pre-I): Vehicle: 27 +/- 9% (n = 8); CL26: 51 +/- 6% (n = 7); P < 0.05). Also, at R35, the voltage required to capture and pace the vehicle-treated hearts was significantly greater than the voltage required to pace the CL26 hearts (P < 0.05). Because the coronary flowrate and leukocyte retention were similar for both groups, the improved recovery observed in the CL26-treated group was not due to either improved flow or to reduced leukocyte retention. Rather, the findings suggest that the beneficial effect of antibody treatment was to attenuate step(s) in the acute inflammatory response that occurred after the initial deposition of leukocytes in the heart.

Animals↗

Machiavellianism: a synthesis of the evolutionary and psychological literatures.

Manipulative strategies of social conduct (Machiavellianism) have been studied by both psychologists and evolutionary biologists. The authors use the psychological literature as a database to test evolutionary hypotheses about the adaptive advantages of manipulative social behavior. Machiavellianism does not correlate with general intelligence and does not consistently lead to real-world success. It is best regarded as 1 of several social strategies, broadly similar to the "defect" strategy of evolutionary game theory, which is successful in some situations but not others. In general, human evolutionary psychology and evolutionary game theory provide useful frameworks for thinking about behavioral strategies, such as Machiavellianism, and identify a large number of specific hypotheses that have not yet been tested by personality and social psychologists.

Animals↗