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By M. Merdarion. Indiana University - Purdue University, Fort Wayne.

Mathematical models aid the controlled discount plavix 75mg, experi- mental dissection of these relations (Nowak and May 2000) discount 75 mg plavix with mastercard. Controlled analysis must be complemented by study of variation and adaptation in natural isolates. Measuring Selection with Population Samples 15 Experimental evolution provides insight into kinetic and mechanistic as- pects of parasite escape from host immunity. Suchexperimental studies clarify selective forces that inuence change at certain amino acid sites. But experimental studies provide only a hint of what actually occurs in natural populations, in which selective pressures and evolutionary dy- namics dier signicantly from those in controlled laboratory studies. It is important to combine experimental insights with analyses of vari- ation in natural populations. In this chapter, I discuss how population samples of nucleotide sequences provide information about natural se- lection of antigenic variation. Ifocuson themes directly related to the goal of this book the syn- thesis between dierent kinds of biological analyses. In particular, I show how analysis of population samples complements studies of mo- lecular structure and experimental evolution. Several books and articles review the methods to analyze population samples and the many dier- ent types of applications (Kimura 1983; Nei 1987; Nee et al. The rst section describes how dierent kinds of natural selection cause dierent patterns of nucleotide substitutions. Thus, the pattern of nucleotide substitutions observed in a population sample of sequences can sometimes be used to infer the kind of selection. The simplest pat- tern concerns the number of nucleotide changes that cause an amino acid substitution (nonsynonymous) relative to the number of nucleotide changes that do not cause an amino acid substitution (synonymous). If natural selection does not aect the relative success of amino acid vari- ants, then nonsynonymous and synonymous nucleotide substitutions occur at the same rate. An excess of nonsynonymous substitutions sug- gests that natural selection favored those changes, providing evidence for positive selection of amino acid replacements. The second section presents two examples of positive selection on parasite antigens. Asampleofnucleotide sequences showed that strong positive selection occurred in a few small regions of the Tams1 antigen, suggesting that those regions have been under strong selection for escape from host immunity. In a sample of 892 nucleotide sequences, 77 of 86 nucleotide changes caused amino acid substitutions, a large excess of nonsynonymous substitutions. Very strong natural selection by host antibodies apparently drives rapid change in Sic. The third section continues with more examplesofpositive selec- tion on parasite antigens. These examples improve on earlier studies by estimating the rates of synonymous and nonsynonymous nucleotide changes for each individual amino acid. This is important because an epitope often requires only one or two amino acid changes to escape from binding by a specic antibody or T cell. Identication of particular amino acid sites under strong selection can conrm predictions for the location of epitopes based on structural data and experimental anal- ysis of escape mutants. Positively selected sites can also suggest the location of new epitopes not found by other methods and provide clues about which amino acid variants should be included in multicomponent vaccines. The fourth section turns to recent studies of inuenza A that corre- late amino acid changes at positively selected sites with the subsequent success of the lineage. This correlation between substitutions and t- ness provides an opportunity to predictfuture evolution new variants arising at positively selected sites are predicted to be the progenitors of future lineages. Yearly inuenza A isolates from 1983 to 1997 provided sequences on which to test this prediction method retrospectively. In nine of eleven years, the changes at positively selected sites predicted which lineage would give rise to the future inuenza population. The 64 codons specify 20 dierent amino acids plus a stop signal, leading to an average of 64/21 3dierent codons for each amino acid or stop signal. This degenerate aspect of the code means that some nucleotide substitutions do not change the encoded amino acid or stop signal. Nucleotide substitutions that do not cause an amino acid change are called synonymous; those that do change the encoded amino acid are called nonsynonymous. Synonymous substitutions do not aect the amino acid sequence and therefore should not be aected by natural selection of phenotype. By contrast, nonsynonymous substitutions can be aected by selection because theydochange the encoded protein. Thus, dN >dS measured in a sam- ple of sequences implies that natural selection has favored evolutionary change. This contribution of selection to the rate of amino acid change above the background measured by dS is called positive selection. Par- asite epitopes often show signs of positiveselection as they change to escape recognition by host immunity (Yang and Bielawski 2000). By contrast, negative selection removes amino acid changes, preserv- ing the amino acid sequence against the spread of mutations.

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Frequent shampooing with excessive sebum removal created the need for a synthetic sebum-like substance able to minimize static electricity buy plavix 75mg, increase hair shine cheap 75mg plavix otc, improve hair manageability, and aid in hair styling (10). Thus, hair conditioners were developed to mimic the positive attributes of sebum while avoiding the greasy appearance indicative of dirty hair (Table 2). Conditioners do not damage the hair shaft and can provide protective qualities against heat, combing friction, and trauma. Conditioners also attempt to recondition hair that has been damaged by chemical or mechanical trauma (11). The conditioner effect is temporary, lasting only until it is removed with shampooing, and it requires reapplication. The primary goal of a hair conditioner is to improve manageability by decreasing static electricity. Static electricity is generated following combing or brushing as the hair shafts become negatively charged. These negatively charged shafts repel one another, preventing the hair from remaining in the desired style. Conditioners deposit positively charged ions on the hair shaft and neutralize the electrical charge and minimize frizzy hair. Conditioners also improve hair manageability by decreasing friction between hair shafts through a smoother cuti- cle surface. This is accomplished by lling in the gaps around and between the cuticular scales. A quality hair conditioner can reduce friction between hair shafts by as much as 50% (14). This reduction in friction also aids disentangling of the hair following shampooing. Con- ditioners increase hair gloss primarily by increasing adherence of the cuticular scale to the hair shaft. The conditioner can also coat each individual hair shaft with a shiny material, which also increases light reection (20). Thus, shiny hair, which is equated with healthy hair, is a combina- tion of the physical structure of the hair shaft and surface-modifying conditioning ingredients. Split ends, medically known as trichooptilosis, occur when the cuticle has been removed from the hair shaft and the soft keratin cortex and medulla are exposed to weathering and grooming trauma. The proteins of these structures are unable to withstand the damage and split or fray, much like a damaged textile ber (21). Conditioners temporarily reapproximate the frayed remnants of remaining medulla and cortex until subsequent shampooing. This prevents a frizzy appearance to the distal hair shaft and minimizes hair breakage. Many years ago there was concern that conditioners could create a lm on the hair shafts that was poorly removed with shampoo. Indeed this condition can still occur with insufcient shampooing, however the introduction of silicones into hair conditioners to replace waxes and oils has remedied the situation. Conditioner Formulation Conditioners are available for many different hair types and needs. Typically, a variety of dif- ferent hair-modifying ingredients are combined to yield the nal characteristics of the con- ditioner. The most common conditioning agents and their functions are listed in Table 3 and include quaternaries, lm-formers, proteins, and silicones (22). Quaternary Conditioners The quaternary conditioning agents, also known as quaternaries or quaternary ammonium compounds or quats, are cationic detergents as discussed previously under hair shampoo deter- gents (23). These ingredients are found in both conditioning shampoos and hair conditioners (24). They function to neutralize the negative charge found on the hair shafts thus minimizing static electricity (25). It is the attraction of the positively charged conditioner to the negatively charged hair shafts that allows quat conditioners to resist water rinsing (26). This allows the conditioning agent to remain behind on the hair shafts until subsequent shampooing, provid- ing long-lasting hair beautication. Film-forming Conditioners The second category of conditioning agents is known as lm-formers. This improves hair luster by lling in the protein voids within the hair shafts and reduces static electricity by neutralizing any charges present on the hair shafts. Film-forming conditioners are traditionally used following towel drying of the hair and are sometimes incorporated into conditioning hair styling agents. These areas of the hair shaft devoid of the cuticle create sites for deposition of conditioner protein, which is hydrolyzed to a molecular weight 1000 to 10,000 Daltons (30). Voids may also be present in the cuticle due to hair dyeing, which disrupts the cuticle through exposure to hydrogen peroxide and/or ammonia, or hair permanent waving, which disrupts the cuticle due to ammonium thio- glycolate exposure. The small molecular weight proteins can penetrate the hair shaft through these voids and increase hair fracture strength by 10%. Nonmedicated Grooming Products and Beauty Treatments 63 the proteins diffuse out with subsequent shampooing.