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Opposing selective forces for expression of the gonococcal lactoferrin receptor.

All isolates of Neisseria gonorrhoeae express receptors that bind human transferrin (Tf). Although lactoferrin (Lf) is abundant on mucosa and in purulent exudates, many gonococci do not express an Lf receptor. The naturally occurring Lf receptor deletion mutant FA1090 (LbpB-LbpA-) is infectious, but a Tf receptor mutant of FA1090 is unable to infect male volunteers [Cornelissen, C.N., Kelley, M., Hobbs, M.M., Anderson, J.E., Cannon, J.G., Cohen, M.S., and Sparling, P.F. (1998) Mol Microbiol 27: 611-616]. Here, we report that expression of an Lf receptor in the absence of the Tf receptor was sufficient for infection, and that expression of both Lf and Tf receptors resulted in a competitive advantage over a strain that made only the Tf receptor in mixed infection of male volunteers. We confirmed that nearly 50% of clinical isolates do not make an Lf receptor. Surprisingly, about half of geographically diverse Lf - isolates representing many different auxotypes and porin serovars carried an identical lbpB lbpA deletion. Among Lf+ strains, all produced the integral outer membrane protein LbpA, but 70% did not express the lipoprotein LbpB. Thus, there are apparently selective pressures for expression of the Lf receptor in the male urethra that are balanced by others against expression of the Lf receptor in niches other than the male urethra.

Bacterial Outer Membrane Proteins↗

Entrainment of a spatially extended nonlinear structure under selective forcing.

The response of a nonlinear state to a variable forcing periodic in space is studied in an extended dynamical system consisting of a liquid crystal layer driven to convection. Both the statics and the dynamics of the entrainment and the locking effects are analyzed. The dynamics of the evolution are controlled by topological singularities that allow a diffusion of the phase. The mechanisms involved are related to the role of the defects in systems undergoing spontaneous symmetry breakings.

Journal Article↗

Forced selection of a human immunodeficiency virus type 1 variant that uses a non-self tRNA primer for reverse transcription: involvement of viral RNA sequences and the reverse transcriptase enzyme.

Human immunodeficiency virus type 1 uses the tRNA(3)(Lys) molecule as a selective primer for reverse transcription. This primer specificity is imposed by sequence complementarity between the tRNA primer and two motifs in the viral RNA genome: the primer-binding site (PBS) and the primer activation signal (PAS). In addition, there may be specific interactions between the tRNA primer and viral proteins, such as the reverse transcriptase (RT) enzyme. We constructed viruses with mutations in the PAS and PBS that were designed to employ the nonself primer tRNA(Pro) or tRNA(1,2)(Lys). These mutants exhibited a severe replication defect, indicating that additional adaptation of the mutant virus is required to accommodate the new tRNA primer. Multiple independent virus evolution experiments were performed to select for fast-replicating variants. Reversion to the wild-type PBS-lys3 sequence was the most frequent escape route. However, we identified one culture in which the virus gained replication capacity without reversion of the PBS. This revertant virus eventually optimized the PAS motif for interaction with the nonself primer. Interestingly, earlier evolution samples revealed a single amino acid change of an otherwise well-conserved residue in the RNase H domain of the RT enzyme, implicating this domain in selective primer usage. We demonstrate that both the PAS and RT mutations improve the replication capacity of the tRNA(1,2)(Lys)-using virus.

Amino Acid Substitution↗

Soluble oligovalent antigen--antibody complexes. II. The effect of various selective forces upon relative stability of isolated complexes.

Soluble oligovalent antigen--antibody complexes were isolated and analysed by ultracentrifugation to assess the effect of several forces upon the composition and stability of soluble complexes. Complexes were prepared with fluorescein (F) conjugates of rabbit serum albumin (RSA) or thyroglobulin (RTg) and high affinity rabbit anti-F antibodies. Isolated complexes containing two antigen molecules (Ag2 complexes) tended to dissociate and form an equilibrium with complexes containing one antigen molecule (Ag1 complexes). This equilibrium was thermolabile, concentration dependent and affected by the original combining ratio and the area in the gradient from which complexes were harvested. Small amounts of free antibody dissociated from soluble complexes also to form a dynamic equilibrium; this equilibrium was much less affected by the above parameters. The data support the concept that complexes grow in size by a process analogous to polymerization of simple subunits and that the driving forces for polymerization are of a lower order of magnitude and more affected by physical variables than the primary reaction between antibody and its antigen.

Antibody Affinity↗

Adaptive immunity is the primary force driving selection of equine infectious anemia virus envelope SU variants during acute infection.

Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infection in horses. The appearance of antigenically distinct viral variants during recurrent viremic episodes is thought to be due to adaptive immune selection pressure. To test this hypothesis, we evaluated envelope SU cloned sequences from five severe combined immunodeficient (SCID) foals infected with EIAV. Within the SU hypervariable V3 region, 8.5% of the clones had amino acid changes, and 6.4% had amino acid changes within the known cytotoxic T lymphocyte (CTL) epitope Env-RW12. Of all the SU clones, only 3.1% had amino acid changes affecting potential N-linked glycosylation sites. In contrast, a much higher degree of variation was evident in SU sequences obtained from four EIAV-infected immunocompetent foals. Within V3, 68.8% of the clones contained amino acid changes, and 50% of the clones had amino acid changes within the Env-RW12 CTL epitope. Notably, 31.9% of the clones had amino acid changes affecting one or more glycosylation sites. Marked amino acid variation occurred in cloned SU sequences from an immune-reconstituted EIAV-infected SCID foal. Of these clones, 100% had amino acid changes within V3, 100% had amino acid changes within Env-RW12, and 97.5% had amino acid changes affecting glycosylation sites. Analysis of synonymous and nonsynonymous nucleotide substitutions revealed statistically significant differences between SCID and immunocompetent foals and between SCID foals and the reconstituted SCID foal. Interestingly, amino acid selection at one site occurred independently of adaptive immune status. Not only do these data indicate that adaptive immunity primarily drives the selection of EIAV SU variants, but also they demonstrate that other selective forces exist during acute infection.

Acute Disease↗

Hamilton's indicators of the force of selection.

To quantify the force of selection, Hamilton [Hamilton, W. D. (1966) J. Theor. Biol. 12, 12-45] derived expressions for the change in fitness with respect to age-specific mutations. Hamilton's indicators are decreasing functions of age. He concluded that senescence is inevitable: survival and fertility decline with age. I show that alternative parameterizations of mutational effects lead to indicators that can increase with age. I then consider the case of deleterious mutations with age-specific effects. In this case, it is the balance between mutation and selection pressure that determines the equilibrium number of mutations in a population. In this balance, the effects of different parameterizations cancel out, but only to a linear approximation. I show that mutation accumulation has little impact at ages when this linear approximation holds. When mutation accumulation matters, nonlinear effects become important, and the parameterizations of mutational effects make a difference. The results also suggest that mutation accumulation may be relatively unimportant over most of the reproductive lifespan of any species.

Aging↗

U.S. Air Force pilot selection and training methods.

BACKGROUND: U.S. Air Force (USAF) pilot selection and training procedures have changed substantially in the last several years. Pilot selection procedures were augmented with the introduction of computer-based testing to assess pilot aptitude. Training procedures have changed in an effort to modernize the training fleet and provide better, more specialized training earlier in the training process. RESULTS: Despite several studies showing the utility of USAF pilot aptitude tests for predicting training performance, results of a recent policy capturing study suggest that this information is often ignored by pilot candidate selection boards. The two largest sources of USAF pilot trainees relied heavily on measures of officership when making selection decisions. Cumulative research findings suggest that USAF pilot selection decisions could be improved by making better use of currently available personnel attribute data. Further improvements could be expected from the addition of a structured selection interview and measures of personality.

Humans↗

The use of AFLP to find an informative SNP: genetic differences across a migratory divide in willow warblers.

We used the amplified fragment length polymorphism (AFLP) method to obtain genetic markers distinguishing two subspecies of willow warblers Phylloscopus trochilus that have different migratory behaviours but are not differentiated in mitochondrial DNA or at several microsatellite loci. With the inverse-polymerase chain reaction (PCR) approach we converted a dominant AFLP-marker to a codominant single nucleotide polymorphism (SNP). Across Scandinavia we typed 621 birds at the SNP locus AFLP-WW1 and we found a sigmoid change in allele frequencies centred around 62 degrees latitude. North of the latitudinal cline was a west-east cline. Both clines are narrower than one would expect from dispersal distances in willow warblers, which suggests that these are maintained by selection. The latitudinal cline at the locus AFLP-WW1 is paralleled by changes in several other traits, all of which might be maintained by a single selective force. The most plausible selection factor that we have identified is selection against hybrids because of inferior migratory behaviour. The selective force maintaining the east-west cline is less obvious. We discuss alternatives to the selection scenario, involving colonization history and asymmetric gene flow.

Animal Migration↗

A synthetic review of the theory of gynodioecy.

Cytoplasmic male sterility alleles (CMS) and corresponding nuclear restorer alleles (R) determine gender expression in gynodioecious populations. In this article, we combine cytonuclear epistasis theory, multilevel selection theory, and resource allocation theory to partition the many selective forces acting in gynodioecious species. This description of selective forces reveals that the notion that genomic conflict leads to the spread of restorers is erroneous. By elucidating the effect of each selective force alone and in combination with the others, our approach shows why change in a single parameter, such as the degree of restorer dominance or the cost of restoration, can result in a myriad of opposing selective effects, making it difficult to test theoretical predictions in experimental systems. In particular, our approach allows us to identify the harmonic mean resource allocation between pollen and ovules and the attendant Fisherian selection as playing a critical role in the evolution of the restorer allele and gender polymorphism. We use this conceptual framework to propose empirical methods that emphasize the role of Fisherian selection acting in gynodioecious populations. Because our approach increases the number and specificity of theoretical predictions, we argue that it provides a better framework for empirical testing.

Cytoplasm↗

Male-female performance on U.S. Air Force pilot selection tests.

BACKGROUND: Recently, the U.S. Air Force conducted several studies to examine sex differences on pilot selection tests and training performance. METHODS: Research has focused on mean score performance, the structure of ability, the predictive utility of pilot selection tests, and the causal role of ability and prior flying knowledge in the acquisition of additional flying knowledge and flying skills. DISCUSSION: Despite male-female mean score differences on pilot selection tests, confirmatory factor analyses indicated that the same factors were being measured for both groups. In studies of predictive bias, no evidence of differential validity was found for male vs. female pilot trainees. An examination of causal models of ability and prior flying knowledge on the acquisition of additional flying knowledge and flying skills showed similar structure for men and women.

Adult↗

On the nature of the forces controlling selectivity in the high performance capillary electrochromatographic separation of peptides.

In this minireview, the nature of the forces controlling selectivity in the high performance capillary electrochromatographic (HP-CEC) separation of peptides has been examined. For uncharged and charged peptides, a synergistic interplay occurs in HP-CEC systems between adsorptive/partitioning events and electrokinetically driven motion. Moreover, at high field strengths, both bulk electrophoretic migration and surface electrodiffusion occur. Thus, the migration behavior of peptides in different HP-CEC systems can be rationalized in terms of the combined consequences of these various processes. Moreover, in HP-CEC, the buffer electrolyte interacts with both the peptide analytes and the sorbent as bulk phenomena. These buffer-mediated processes control the solvational characteristics, ionization status and conformational behavior of the peptides as well as regulate the double-layer properties of the sorbent, and the ion flux and electro-osmotic flow characteristics of the HP-CEC system per se. These buffer electrolyte effects mediate mutual interactions between the peptide and the sorbent, irrespective of whether the interaction occurs at the surface of microparticles packed into a capillary, at the surface of a contiguous monolithic structure formed or inserted within the capillary or at the walls of the capillary as is the case with open tubular HP-CEC. Diverse molecular and submolecular forces thus coalesce to provide the basis for the different experimental modes under which HP-CEC can be carried out. As a consequence of this interplay, experimental parameters governing the separation of peptides in HP-CEC can be varied over a wide range of conditions, ensuring numerous options for enhanced selectivity, speed, and resolution of peptides. The focus of the peptide separation examples presented in this minireview has been deliberately restricted to the use of HP-CEC capillaries packed with n-alkyl-bonded silicas or mixed-mode strong ion exchange sorbents, although other types of sorbent chemistries can be employed. From these examples, several conclusions have been drawn related to the use of HP-CEC in the peptide sciences. These observations confirm that variation of a specific parameter, such as the pH or the content of the organic solvent modifier in the buffer electrolyte, simultaneously influences all other physicochemical aspects of the specific HP-CEC separation. Peptide selectivity in HP-CEC thus cannot be fine-tuned solely through the use of single parameter optimization methods. In this context, HP-CEC differs significantly from the analogous reverse phase high performance liquid chromatography (RP-HPLC) procedures with peptides. Rather, more sophisticated multiparameter optimization procedures, involving knowledge of (a) the field strength polarity, (b) its contour and flux characteristics, (c) effects of buffer electrolyte composition and pH, (e) the influence of the temperature, and (f) the impact of the sorbent characteristics, are required if the full capabilities offered by HP-CEC procedures are to be exploited. In this minireview, the HP-CEC migration behavior of several different sets of synthetic peptides has been examined, and general guidelines elaborated from these fundamental considerations to facilitate the interpretation and modulation of peptide selectivity in HP-CEC.

Chromatography, Micellar Electrokinetic Capillary↗

A method for detecting positive selection at single amino acid sites.

A method was developed for detecting the selective force at single amino acid sites given a multiple alignment of protein-coding sequences. The phylogenetic tree was reconstructed using the number of synonymous substitutions. Then, the neutrality was tested for each codon site using the numbers of synonymous and nonsynonymous changes throughout the phylogenetic tree. Computer simulation showed that this method accurately estimated the numbers of synonymous and nonsynonymous substitutions per site, as long as the substitution number on each branch was relatively small. The false-positive rate for detecting the selective force was generally low. On the other hand, the true-positive rate for detecting the selective force depended on the parameter values. Within the range of parameter values used in the simulation, the true-positive rate increased as the strength of the selective force and the total branch length (namely the total number of synonymous substitutions per site) in the phylogenetic tree increased. In particular, with the relative rate of nonsynonymous substitutions to synonymous substitutions being 5.0, most of the positively selected codon sites were correctly detected when the total branch length in the phylogenetic tree was > or = 2.5. When this method was applied to the human leukocyte antigen (HLA) gene, which included antigen recognition sites (ARSs), positive selection was detected mainly on ARSs. This finding confirmed the effectiveness of the present method with actual data. Moreover, two amino acid sites were newly identified as positively selected in non-ARSs. The three-dimensional structure of the HLA molecule indicated that these sites might be involved in antigen recognition. Positively selected amino acid sites were also identified in the envelope protein of human immunodeficiency virus and the influenza virus hemagglutinin protein. This method may be helpful for predicting functions of amino acid sites in proteins, especially in the present situation, in which sequence data are accumulating at an enormous speed.

Amino Acid Substitution↗

From community to clients: the professionalisation of HIV prevention among gay men and its implications for intervention selection.

Forces at work are described which encourage professionalisation and a reliance on one on one HIV prevention interventions among gay men. Community involvement is intrinsically linked to epidemic phases; when the threat diminishes, so does the community's ability to sustain community level interventions. The area of structural and environmental interventions, which can reinforce safe behaviour when community interest in collective action wanes, provides a potential complementary solution for prevention workers, researchers, and funders alike.

Adult↗

On the homology of structures and Hox genes: the vertebral column.

Research on expression patterns of Hox genes has revealed a surprisingly high conservation among vertebrates. In agreement with this conservation, a correlation has been found between the anterior limits of expression areas of certain Hox genes and the borders between morphological regions of the vertebral axis. These similarities are striking and important, but also counterintuitive, unless there are strong selection pressures to protect this conservatism. It is important to identify the selective forces that maintain these conservative networks. These selective forces can be due to pleiotropy or to internal selection. Discussed are the selective factors that are involved in the evolutionary constraint on the number of cervical vertebral numbers in mammals. Factors involved are due to internal selection and involve susceptibility to cancer, stillbirths and neuronal problems. It is intriguing how similar genetic networks can lead to fundamentally different animals. Clearly the same genes are used for different purposes. It is therefore important to try to find these differences. The search, for homology between organisms, and the enthusiasm about similarities that come with it, at times impedes the discovery of such differences. I have searched the literature for differences within vertebrates in the functioning and expression patterns of Hox genes during the development of the vertebral axis. The ensuing implications for homology of structures and genes are discussed. The vertebral column is a promising model system for the evaluation of the relationship between homologous Hox genes and homologous structures because of the large conservation of Hox gene expression patterns along the anterior axis. However, extensive remodelling of the vertebrate column indicates that important changes in the genetic basis must have taken place. A survey of the literature indicates that the correlation between Hox gene expression areas and vertebral regions is not such that one can predict the borders between vertebral regions on the basis of Hox gene expression patterns. The involvement of Hox genes in the development of identity of vertebrae is complex and the problems regarding the value of gene expression patterns for the determination of anatomical homology are discussed.

Animals↗