Search PubMed⌕ Search

Biomedical subjects

C I Wu

Publications and source records attributed to C I Wu.

At least 55 records · Page 3Linked to original sources

Support from spouse as mediator and moderator of the disruptive influence of economic strain on parenting.

A model is presented regarding associations between economic strain, support from spouse, and quality of parenting. The model was tested using a sample of 451 2-parent families, each of which included a seventh grader (age 12-13). Parent and adolescent reports, as well as observational ratings, were used as indicators of constructs. Analysis using structural equation modeling procedures indicated that level of spouse support was positively related to supportive parenting, whereas economic strain operated to undermine parental involvement. As posited, economic strain produced its effect through a direct relation with parenting and indirectly through its association with spouse support. These findings held for mothers and fathers, regardless of the gender of the child. Spouse support moderated the impact of economic strain on supportive parenting for mothers but not fathers. Possible explanations for this gender difference are presented.

Adult↗

Inferences of species phylogeny in relation to segregation of ancient polymorphisms.

Standard formulas of gene frequency change under genetic drift are used to derive the probability of obtaining incorrect phylogenetic information for three species due to segregation of ancient polymorphisms. This probability depends upon the level of polymorphisms at the time of speciation and is generally quite high unless the two speciation events are far apart in time. If phylogenetic data from multiple loci are available, a likelihood ratio test can be used to reject the null hypothesis in favor of the best phylogeny. The appropriate null hypothesis is either a trichotomy or an alternative phylogeny, depending on the data set. The likelihood ratios required for accepting the best phylogeny are given. These ratios are obtained by exact enumeration when the number of loci is small (n less than 15) and by an asymptotic approach for larger n's. In general, more than five loci are needed to resolve the species phylogeny.

Alleles↗

Molecular analysis of the responder satellite DNA in Drosophila melanogaster: DNA bending, nucleosome structure, and Rsp-binding proteins.

The Responder (Rsp) locus of Drosophila melanogaster, the target locus of segregation distortion, is a satellite DNA array. This repeat array imparts some fitness advantage to the chromosomes bearing it. In this paper, we report the following three related molecular properties of this satellite repeat: (1) Sequence-directed curvature--On a polyacrylamide gel, Rsp-containing fragments migrate slower than would be predicted on the basis of their physical sizes. The extent of migration retardation correlates with the size and position of the Rsp sequence in a DNA fragment, suggesting that Rsp DNA is bent. The bending is shown to be affected by a DNA-binding drug (Hoechst 33258). (2) Nucleosome structure--Nucleosomes associated with Rsp repeats have an unusual spacing pattern. Instead of being spaced at approximately 190-bp intervals as is the bulk chromatin, they are separated at approximately 240-bp intervals, roughly the size of a dimeric Rsp repeat. The nucleosomal structure in the Rsp region is preferentially disrupted by Hoechst 33258, whereas the bulk chromatin appears to be insensitive to the drug. (3) Rsp-DNA binding proteins--Gel mobility-shift assays using nuclear extracts from pupae and end-labeled Rsp repeat demonstrate the presence of three distinct DNA-protein complexes. Competition assays suggest that these complexes are specific to the Rsp sequence, and two of these nucleoprotein complexes seem to be influenced by the presence of Hoechst 33258. The observed complexes are formed by nonhistone proteins of somatic origin and may be related to the normal functions of Rsp, rather than to the germ-line segregation distortion activities.

Animals↗

Fitness reduction associated with the deletion of a satellite DNA array.

Satellite DNA refers to a class of tandem repeats of very simple sequences, usually A + T or G + C rich, which form a satellite band on a CsCl gradient. Their ubiquity and abundance in higher eukaryotes have led to speculation about their functions. It has often been suggested that satellite DNAs are merely innocuous genetic parasites or comprise 'junk' DNA. The recent identification of an array of satellite DNA repeats as the Responder (Rsp) locus of Drosophila melanogaster provides a new perspective on these elements. Rsp is in the centromeric heterochromatin of most natural second chromosomes. It causes spermatids bearing it to degenerate after meiosis when the homologous second chromosome is a Segregation Distorter (SD) chromosome. That is, SD targets the Rsp locus on its homologue for destruction during spermatogenesis, causing meiotic drive. Why then does the Rsp locus, a large array of satellite repeats, exist at all? One plausible explanation is that its existence contributes to the fitness of flies bearing it, compensating for the loss through meiotic drive. A direct demonstration of the usefulness of any family of satellite DNA is to compare the fitnesses of individuals with and without it. Previously, such an experiment has been difficult because the absence of a characteristic phenotype has precluded an efficient selection of deletion mutations. In this report we attempt to demonstrate a fitness reduction associated with the deletion of Rsp satellite DNA as well as the life stages at which such a reduction occurs.

Animals↗

[Effect of increasing amounts of clonidine during hyperbaric tetracaine spinal anesthesia].

The effect of adding clonidine to hyperbaric tetracaine spinal anesthesia was investigated in 60 ASA class I-II patients scheduled for orthopedic and lower abdominal surgery. The subjects were randomly allocated into 4 groups. All patients received tetracaine 10 mg in 10% glucose solution 2 mL. Patients in group 1 received above medication and were the control group, patients in the other groups received tetracaine plus increasing dosages of clonidine: 15 microgram (Gr.2), 30 microgram (Gr.3), and 45 microgram (Gr.4). The segmental level of sensory loss was tested by the pinprick method using a 23 G needle. The three clonidine groups had significantly increased in the sensory regression time to L1 level (by 42, 47, 60% respectively), and also had significantly increased motor complete recovery time (by 48, 70, 74% respectively), but the incidence of hypotension and bradycardia was increased in the clonidine 0.045 mg group. It is concluded that addition of 15 or 30 microgram clonidine may be useful as a means of increasing the duration of hyperbaric tetracaine spinal anesthesia.

Adult↗

Association between a satellite DNA sequence and the Responder of Segregation Distorter in D. melanogaster.

A large array of satellite DNA sequences are always associated with the Responder (Rsp) element of Segregation Distorter in D. melanogaster. In the appropriate genetic backgrounds, Rsp causes aberrant chromatin condensation in spermiogenesis, leading to dysfunction of sperm carrying Rsp, and meiotic drive. The repeat array is deleted or translocated to the Y chromosome whenever Rsp is. Moreover, the translocation of part of Rsp to Y is associated with the translocation of an incomplete repeat array. The number of repeats among 35 independently derived chromosomes correlates nearly perfectly with sensitivity to distortion. We hypothesize that this satellite repeat array represents Responder itself. Finally, the molecular structure of this locus is extremely variable, indicating a very active process of change.

Animals↗

Molecular evolution of intergenic DNA in higher primates: pattern of DNA changes, molecular clock, and evolution of repetitive sequences.

A 3.1-kb intergenic DNA fragment located between the psi beta-globin and delta-globin genes in the beta-globin gene cluster was cloned from gorilla, orangutan, rhesus monkey, and spider monkey, and the nucleotide sequence of each fragment was determined. The phylogeny of these four sequences, together with two previously published allelic sequences from humans and one from chimpanzee, was constructed, and the accumulation of mutations in the region was analyzed. The sites of base substitutions are not evenly distributed within the region: two Alu repeats have accumulated 0.21 + 0.02 substitutions/site with 0.15 + 0.008 substitutions/site in the remainder of the fragment. The occurrence of substitutions at neighboring sites is more frequent than would be expected if they were independent. The observed excesses disappear when ancestral -CG- dinucleotide sites are excluded. The phylogenetic relationships of the sequences indicate that the human sequence shares a most recent coancestor with the chimpanzee sequence. The data also show that great apes have accumulated fewer mutations in this part of the genome than has the rhesus monkey. The relative rates of accumulation of 12 kinds of nucleotide substitution in the region during primate evolution are asymmetric in the DNA strands. From these rates of accumulation, the origin of a simple stretch of sequence near the 3' end of the 3.1-kb fragment was deduced to be a sequence comprising 50% T and 50% C on one strand. The two oppositely oriented Alu sequences in the 3.1-kb region were inserted at their present positions before the divergence of the New-World monkeys from other lineages. Our analysis shows that the nucleotide sequences of the two Alu repeats in spider monkey are unexpectedly similar both to each other and to the deduced ancestral sequence of Alu repeats. The data suggest that there has been some type of recombinational event between the spider monkey Alu repeats but that it was not a simple gene conversion.

Animals↗

Evolution of cytochrome c genes and pseudogenes.

A statistical analysis of the nucleotide sequences of cytochrome c genes from four species of animals and two of yeast and of cytochrome c pseudogenes from rat, mouse, and human was conducted. It was estimated that animals and yeast diverged 1.2 billion years ago, that the two duplicated genes DC3 and DC4 in Drosophila diverged 520 million years ago, and that the two duplicated genes Iso-1 and Iso-2 in the yeast Saccharomyces cerevisiae diverged 200 million years ago. DC3 is expressed at a low level and has evolved 3 times faster than DC4. This observation supports the neutralist view that relaxation of functional constraints is a more likely cause of accelerated evolution following gene duplication than is advantageous mutation. All the rodent pseudogenes examined appear to be processed pseudogenes derived directly from the functional genes, and most of them apparently arose after the mouse-rat split. No event of gene conversion could be detected between any pair of the rodent pseudogenes. Our analysis suggests that the human cytochrome c gene has evolved at a rate comparable to the average rate for pseudogenes, whereas some human cytochrome c pseudogenes have evolved at an exceptionally low rate.

Animals↗

Evidence for higher rates of nucleotide substitution in rodents than in man.

When the coding regions of 11 genes from rodents (mouse or rat) and man are compared with those from another mammalian species (usually bovine), it is found that rodents evolve significantly faster than man. The ratio of the number of nucleotide substitutions in the rodent lineage to that in the human lineage since their divergence is 2.0 for synonymous substitutions and 1.3 for nonsynonymous substitutions. Rodents also evolve faster in the 5' and 3' untranslated regions of five different mRNAs; the ratios are 2.6 and 3.1, respectively. The numbers of nucleotide substitutions between members of the beta-globin gene family that were duplicated before the man-mouse split are also higher in mouse than in man. The difference is, again, greater for synonymous substitutions than for nonsynonymous substitutions. This tendency is more consistent with the neutralist view of molecular evolution than with the selectionist view. A simple explanation for the higher rates in rodents is that rodents have shorter generation times and, thus, higher mutation rates. The implication of our findings for the study of molecular phylogeny is discussed.

Animals↗

A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes.

A new method is proposed for estimating the number of synonymous and nonsynonymous nucleotide substitutions between homologous genes. In this method, a nucleotide site is classified as nondegenerate, twofold degenerate, or fourfold degenerate, depending on how often nucleotide substitutions will result in amino acid replacement; nucleotide changes are classified as either transitional or transversional, and changes between codons are assumed to occur with different probabilities, which are determined by their relative frequencies among more than 3,000 changes in mammalian genes. The method is applied to a large number of mammalian genes. The rate of nonsynonymous substitution is extremely variable among genes; it ranges from 0.004 X 10(-9) (histone H4) to 2.80 X 10(-9) (interferon gamma), with a mean of 0.88 X 10(-9) substitutions per nonsynonymous site per year. The rate of synonymous substitution is also variable among genes; the highest rate is three to four times higher than the lowest one, with a mean of 4.7 X 10(-9) substitutions per synonymous site per year. The rate of nucleotide substitution is lowest at nondegenerate sites (the average being 0.94 X 10(-9), intermediate at twofold degenerate sites (2.26 X 10(-9)). and highest at fourfold degenerate sites (4.2 X 10(-9)). The implication of our results for the mechanisms of DNA evolution and that of the relative likelihood of codon interchanges in parsimonious phylogenetic reconstruction are discussed.

Amino Acid Sequence↗

Nonrandomness of point mutation as reflected in nucleotide substitutions in pseudogenes and its evolutionary implications.

We have obtained a revised estimate of the pattern of point mutation by considering more pseudogene sequences. Compared with our previous estimate, it agrees better with expectations based on the double-strand structure of DNA. The revised pattern, like the previous one, indicates that mutation occurs nonrandomly among the four nucleotides. In particular, the proportion of transitional mutations (59%) is almost twice as high as the value (33%) expected under random mutation. The same high proportion of transitions is observed in synonymous substitutions in genes. The proportion of transitional changes observed among electrophoretic variants of human hemoglobin is about the same as that predicted by the revised pattern of mutation. We also show that nonrandom mutation increases, by about 15%, the proportion of synonymous mutations due to single-nucleotide changes in the codon table, and increases, from 10% to 50%, the rate of synonymous mutation in the seven genes studied. However, nonrandom mutation reduces (by about 10%) the proportion of polar changes among nonsynonymous mutations in a gene. As far as single-nucleotide changes (in the codon table) are concerned, nonrandom mutation only slightly favors relatively conservative amino acid interchanges, and has virtually no effect on the proportions of radical changes and nonsense mutations.

Amino Acid Sequence↗

The fate of autosomal modifiers of the sex-ratio trait in drosophila and other sex-linked meiotic drive systems.

A model is proposed to analyze the behavior of autosomal suppressor modifiers of "Sex-Ratio" meiotic drive in drosophila. These modifiers, if neutral in fitness, are expected to increase because they tend to be associated with the rare sex (males). However, selection operating on the sex-linked drive locus will sometimes act against autosomal modifiers as well because the two loci are always in gametic phase disequilibrium. Conditions under which modifiers will not increase are presented in terms of the relative fitness of the sex-linked drive locus. To prevent the increase of modifiers, the fitness of Sex-Ratio males relative to Standard males has to be no greater than 0.3 and there has to be overdominance in females. This model integrates findings from the search for modifiers and results from the measurement of fitness.

Animals↗