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C Wills

Publications and source records attributed to C Wills.

At least 37 records · Page 2Linked to original sources

An educational intervention as decision support for menopausal women.

The purpose of this study was to develop and test a decision support intervention (DSI) to assist women to make and act on informed decisions that are consistent with their values in the area of menopause and hormone replacement therapy (HRT). Mode and intensity of intervention were tested in midlife women (N = 248), randomly assigned to one of three intervention formats: written information only, guided discussion, or personalized decision exercise. Data were collected over 12 months. Knowledge, decisional conflict, satisfaction with health care provider, and self-efficacy improved following intervention and were maintained for 12 months for all groups. Women's adherence to their own plans over 12 months was 59% (exercise), 76% (calcium intake), and 89% (HRT). Carefully written information is effective in promoting knowledge, adherence, and satisfaction among well-educated, interested women. It was concluded that women can understand complex information, including tradeoffs regarding treatment options. Women will adhere to their own plans, suggesting that consumer rather than provider plans may be the more appropriate gold standard for measuring adherence.

Adult↗

Long, polymorphic microsatellites in simple organisms.

We have examined the phylogenetic distribution of the longest, perfect microsatellites in GenBank. Despite the large contributions of model higher-eukaryotic organisms to GenBank, the selective cloning of long microsatellites from these organisms as genetic markers, and the relative lack of concentration on the microsatellites in lower eukaryotes and prokaryotes, we found that simple organisms, defined here as slime molds, fungi, protists, prokaryotes, viruses, organelles and plasmids, contributed 78 of the 375 examined sequences. These 78 simple-organism microsatellites are characterized predominantly by trinucleotide repeats, nearly half of which lie in exons, and in general show a bias towards A+T rich motifs. Simple-organism microsatellites represented more than once in GenBank displayed length polymorphisms when independent clones were compared. These facts collectively raise speculation as to the role of these 'junk' sequences in such highly economical genomes, especially when precise changes in long microsatellites are known to regulate critical virulence factors in several prokaryotes. Regardless of their biological significance, simple-organism microsatellites may provide a general source of molecular markers to track disease outbreaks and the evolution of microorganisms in unprecedented detail.

Animals↗

Significant competitive advantage conferred by meiosis and syngamy in the yeast Saccharomyces cerevisiae.

The presumed advantages of genetic recombinations are difficult to demonstrate directly. To investigate the effects of recombination and background heterozygosity on competitive ability, we have performed serial-transfer competition experiments between isogenic sexual and asexual strains of the yeast Saccharomyces cerevisiae. The members of these diploid pairs of strains differed only in being heterozygous (sexual) or homozygous (asexual) at the mating type or MAT locus. Competing pairs had either a completely homozygous or a heterozygous genetic background, the latter being heterozygous at many different loci throughout the genome. A round of meiotic recombination (automixis) conferred a large and statistically significant enhancement of competitive ability on sexual strains with a heterozygous genetic background. By contrast, in homozygous background competitions, meiosis decreased the sexual strains' initial relative competitive ability. In all cases, however, the sexual strains outcompeted their isogenic asexual counterparts, whether meiotic recombination had occurred or not. In some genetic backgrounds, this was due in part to an overdominance effect on competitive advantage of heterozygosity at the MAT locus. The advantage of the sexual strains also increased significantly during the course of the homozygous background competitions, particularly when meiosis had occurred. This latter effect either did not occur or was very weak in heterozygous background competitions. Overall, sexual strains with heterozygous genetic backgrounds had a significantly higher initial relative competitive ability than those with homozygous backgrounds. The advantage of mating type heterozygosity in this organism extends far beyond the ability to recombine meiotically.

Biological Evolution↗

Another nail in the coffin of the multiple-origins theory?

While mitochondrial sequences can be used to probe the time and place of the mitochondrial 'Eve,' nuclear genes can be used to ask a slightly different question: when did humans (members of the genus Homo) or their hominid precursors (the hominids) first leave Africa and fan out over Asia and Europe? If they did so recently, it seems likely that there was a recent African origin of our species, Homo sapiens, rather than multiple origins in various parts of the Old World. A recent paper uses minisatellite data to make the argument that the departure from Africa happened very recently indeed. An alternative explanation for the data is that there was no single and irreversible departure from Africa, but that some peoples migrated back and forth between Africa and the rest of the Old World over the last few tens of thousands of years. For this and other reasons, putting a single date on the farewell to Africa remains problematical.

Africa↗

Improving the analysis of phylogenetic data.

Methods of phylogenetic analysis are presented that result in corrections of highly biased data sets, particularly those in which there are great differences between mutation and/or substitution rates from one nucleotide site to another along a DNA sequence. Two approaches are discussed. In the first, pairwise comparisons of a set of sequences are used to determine whether the most recent substitutions take place at the sites that are most polymorphic--that is, where the mutational "hot spots" are located. In the second, a "topiary pruning" method is used to remove selectively the bases in the data set that are most likely to occupy these hot spots and therefore to result in homoplastic substitutions. The two methods combined yield new and substantially older estimates of the time at which the mitochondrial Eve lived, and increase the likelihood that she lived in Africa. In these data, transversions provide a more satisfactory yardstick for phylogenetic analysis than transitions, because there is no detectable tendency for transversions to occur at mutational hot spots.

Africa↗

Use of polymorphic short and clustered coding-region microsatellites to distinguish strains of Candida albicans.

We describe the identification of polymorphic microsatellite loci in the pathogenic yeast, Candida albicans. A search for all coding-region microsatellites with more than four repeats that can be found in Candida sequences in GenBank was conducted. Nine such microsatellite sequences consisting of trinucleotide motifs were found. Three of these were perfect microsatellites while the remaining six sequences were found in one imperfect microsatellite and two compound microsatellites. Because of the close proximity of some of these repeats, all could be assayed with six PCR primer pairs. All of these microsatellite sequences were found in five nuclear genes, ZNF1, CCN1, CPH1, EFG1, and MNT2. Except for a single (CTT)5 serine tract, all coded for polyglutamine tracts. Another locus with seven alleles, a region of the ERK1 protein kinase gene, was also examined, and may be a representative of a new class of highly polymorphic "clustered' microsatellites. Such loci, in which several non-contiguous but closely linked microsatellites are clustered together, may be a useful source of DNA polymorphisms in microorganisms in which long microsatellite sequences are unavailable. All seven regions amplified were polymorphic, having between two and seven variable length alleles in the 11 strains of Candida albicans examined. The results of this and similar searches will facilitate epidemiological and evolutionary studies of Candida and other microorganisms.

Alleles↗

Use of denaturing gradient electrophoresis to determine the distributions of polymorphisms in entire genes in natural populations.

We show here that the method of genomic denaturing gradient electrophoresis (gDGGE) can be used to examine any gene that has been previously cloned and sequenced, and to detect and approximately localize within the gene the majority of its polymorphisms. By using pooled-DNA gDGGE, many different samples can be scanned on a single gel. Further, the patterns on the gels and results from sequencing of some of the alleles shows that a variety of different kinds of polymorphism, ranging from single base changes to more substantial allelic differences, can be distinguished. The extramacrochaetae (emc) gene of Drosophila melanogaster exhibits no polymorphism in its ORF that can be detected by this method, although a rearrangement polymorphism was detected in the 3' downstream region of the gene. The suppressor-of-hairless (Su(H)) gene of D. melanogaster, however, exhibits a variety of polymorphisms in its ORF. Some are small deletions or insertions in a glutamine-rich part of the gene product that would not have been detectable by ordinary screening methods. Many of the polymorphisms detected in this preliminary survey are likely to have an impact on the function of the Su(H) gene product.

Animals↗

Similarity landscapes: a way to detect many structural and sequence motifs in both introns and exons.

When investigators undertake searches of DNA databases, they normally discard large numbers of alignments that demonstrate very weak resemblances to each other, retaining only those that show statistically significant levels of resemblance. We show here that a great deal of information can be extracted from these weak alignments by examining them en masse. This is done by building three-dimensional similarity landscapes from the alignments, landscapes that reveal whether an unusual number of individually nonsignificant alignments tend to match up to a particular region of the query sequence being searched. The power of the search is increased by the use of libraries consisting entirely of introns or of exons. We show that (1) similarity landscapes with a variety of features can be generated from both intron and exon libraries, using introns or exons as query sequences; (2) the landscape features are real and not a statistical artifact; (3) well-known protein motifs used as query sequences can generate various landscape features; and (4) there is some evidence for resemblances between short regions of sequence carried by introns and exons. One possible interpretation of these results is that both introns and exons may have been built up during their evolution from short regions of sequence that as a result are now widely distributed throughout eukaryotic genomes. Such an interpretation would imply that these short regions have common ancestry. Alternatively, the wide sharing of short pieces of DNA may reflect regions with particular structural properties that have arisen through convergent evolution. The similarity-landscape approach can be used to detect such widespread structural motifs and sequence motifs in the genome that might be missed by less-global searches. It can also be used in conjunction with algorithms developed for detecting significant multiple alignments by isolating promising subsets of the databases that can be examined in more detail.

Animals↗

Pleiotropic effects of heterozygosity at the mating-type locus of the yeast Saccharomyces cerevisiae on repair, recombination and transformation.

Sexual (MAT a/alpha) and asexual (MAT a/a) strains of the yeast Saccharomyces cerevisiae, which are completely isogenic except at the MAT locus, were compared in their response to ultraviolet radiation. The effects of UV on survival, mitotic intragenic recombination, photoreactivation, and transformation efficiency with UV-irradiated plasmid DNA were examined. The sexual strain had enhanced survival and higher rates of mitotic intragenic recombination compared with the asexual strain. Exposure to visible light subsequent to irradiation increased the survival of both sexual and asexual strains, and decreased their rates of mitotic intragenic recombination. Similar results were obtained by Haladus and Zuk (1980) in their examination of sexual strains homozygous for rad6-1, and wild-type sexuals. Our sexual strain was also consistently more proficient at transforming plasmid DNA, whether that DNA had been irradiated or not. When pre-irradiated with 25 J/m2 of UV, MAT a/alpha cells transformed more efficiently than MAT a/a cells. When subsequently exposed to light, the ability of these pre-irradiated cells to transform decreased for both strains with increasing irradiation of the plasmid. A smaller decrease in transformation efficiency occurred when cells of both strains were kept in the dark. When pre-irradiated with 100 J/m2, the MAT a/alpha cells showed a 2-fold increase in their transformation efficiency of both irradiated and unirradiated plasmids by up to 2-fold, a phenomenon not seen in the MAT a/a cells even when pre-irradiated with much higher doses of UV. This increase in transformation efficiency was not, however, seen in the MAT a/alpha cells when they were exposed to visible light after UV irradiation. These results suggest that cells with the MAT a/alpha genotype have a UV-inducible system that increases the efficiency of transformation in the absence of visible light. This increase in transformation is not an induced increase in the repair of plasmid DNA, but rather an increase in the ability of pre-irradiated MAT a/alpha cells to take up exogenous DNA. MAT a/a cells do not appear to have a similarly inducible system. To the best of our knowledge, this phenomenon has not been previously reported.

DNA Damage↗

Perinatal outcome and antenatal care in a black South African population.

The relationship between perinatal outcome and antenatal care was investigated at King Edward VIII Hospital, Durban, by a case control retrospective study of pregnancy records in 165 perinatal deaths and 156 infants surviving the perinatal period. 82% of the mothers of live infants had booked for antenatal care compared with only 60% of those who experienced a perinatal death. Hospital booking was associated with a higher infant birthweight. For those who booked earlier there was no reduction in total perinatal mortality or the stillbirth:neonatal death ratio, and many of the mothers of highest risk failed to book. This suggests that the better perinatal outcome in booked mothers may have been secondary to the type of mother who chose to book, rather than the actual antenatal care. To help reduce perinatal mortality, methods must be employed which reach those mothers who are most likely to fail to book.

Birth Weight↗

Human origins.

Explore the source record for details and available documents.

Africa↗

Maintenance of multiallelic polymorphism at the MHC region.

Models that purport to explain the maintenance of MHC polymorphism must be able to explain a variety of phenomena. (1) The range of MHC allele frequencies at some of the loci is very large, with some alleles quite common and many others rare, while at others the range of allele frequencies is far narrower. (2) MHC alleles and their frequencies often have long persistence times, in some cases tens of millions of years. (3) Random-mating populations appear to be in Hardy-Weinberg equilibrium for MHC. (4) There is no obvious, strong and consistent selection pressure yet detected that acts differentially on different MHC genotypes. (5) Because the allelic composition of the MHC polymorphism does change over evolutionary time, the MHC system must be capable of accommodating new alleles with similar properties without destruction of the equilibria that permit the maintenance of the older alleles. In this review I examined the degree to which a large number of models that have been proposed fit these criteria. These include heterosis, marginal overdominance, conditional heterosis, assortative mating, maternal-fetal incompatibility, molecular mimicry, minority advantage, pathogen adaptation, and optimum allele frequency models. Most of the models do poorly at accounting for a number of the above phenomena. The last class, optimum allele frequency models, have the most satisfactory set of properties. However, optimum allele frequency models require mechanisms that somehow "feed back" from the frequency of an allele in the population to the fitness of an organism carrying that allele. Thus, these models require that MHC polymorphisms be maintained by some type of group selection. Evidence for an against optimum allele frequency selection, and ways in which this type of selection might be detected experimentally, are presented.

Alleles↗