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E Beasley

Publications and source records attributed to E Beasley.

5 recordsLinked to original sources

The sequence of the human genome.

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Algorithms↗

Monoamniotic twins: case series and proposal for antenatal management.

OBJECTIVE: To present a case series of antenatally suspected monoamniotic twin gestations managed by a similar set of guidelines. METHODS: Eight women with antenatally suspected monoamniotic twins were identified between 1994 and 1996 in a single perinatal referral area. All were diagnosed sonographically. Management included serial ultrasound studies, frequent nonstress testing, and weekly steroid therapy. Elective cesarean delivery was recommended at 32 weeks unless obstetrically indicated at an earlier age. RESULTS: Monochorionic monoamniotic twins were confirmed at delivery in six women, and one had a pseudomonoamniotic twin. One woman was found to have a monochorionic diamniotic pregnancy at delivery. Of the eight women, three were delivered by elective cesarean at 32 weeks, including the falsely diagnosed case. Three were delivered before 32 weeks because of nonreassuring fetal testing. One was delivered at 25 weeks secondary to hemolysis, elevated liver enzymes, low platelets, and disseminated intravascular coagulation. One was delivered at 33 weeks, after declining elective delivery at 32 weeks, because of death of one twin and nonreassuring testing of the other twin. Morbidity among the live-born infants included severe bronchopulmonary dysplasia (25-week twins), large-bowel perforation (30-week infant), and respiratory distress syndrome and mild bronchopulmonary dysplasia (one 32-week pair). CONCLUSION: Monoamniotic twin pregnancies can be diagnosed reliably by ultrasound alone in most cases. Frequent antenatal testing may show signs of cord compression that may prompt delivery but will not prevent sudden fetal death. Fetal death can occur at greater than 32 weeks' gestation despite intensive fetal surveillance. Elective preterm delivery could be considered to eliminate the uncertain risk of fetal death.

Adult↗

Characterization of effects of anti-beta and anti-beta' monoclonal antibodies on the activity of the RNA polymerase from Escherichia coli.

Monoclonal antibodies directed against antigenic determinants on the beta and beta' subunits of the Escherichia coli RNA polymerase were characterized by using d(A-T)n-directed transcription assays. Antibodies were prepared by using purified subunits as immunogens, and seven anti-beta and five anti-beta' monoclonal antibodies were generated. Inhibitory anti-beta monoclonal antibodies were found to affect RNA polymerase during synthesis of r(A-U)n, abortive initiation of pApU and UpApU, and elongation by preformed ternary complexes. A comparative enzyme study of r(A-U)n synthesis showed the core polymerase to be more sensitive to inhibition by the anti-beta monoclonal antibody than was the holoenzyme. In contrast, the inhibition effected by the anti-beta' monoclonal antibody was found to be 90% or greater for each of the d(A-T)n-directed assays used. The different inhibitory patterns exhibited by the anti-beta and anti-beta' monoclonal antibodies suggest that the beta and beta' subunits engage in different roles during transcription. Kinetic analysis of the abortive initiation reaction in the presence and absence of the inhibitory antibodies resulted in distinctive but complex modes of inhibition. Inhibition by the anti-beta monoclonal antibody 210E8 was noncompetitive with regard to UTP and competitive for UpA incorporation; at increased UpA concentration, the inhibition was completely reversed. Inhibition of the abortive synthesis of UpApU by the anti-beta' monoclonal antibody 311G2 was noncompetitive with regard to both UpA and UTP incorporation. When the preformed ternary elongation complex was used, inhibition by the anti-beta monoclonal antibody was mixed with regard to the ribonucleoside triphosphate substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗