ABSTRACT
The transformer (tra) gene of Drosophila melanogaster occupies an intermediate position in the regulatory pathway controlling all aspects of somatic sexual differentiation. The female-specific expression of this gene's function is regulated by the Sex lethal (Sxl) gene, through a mechanism involving sex-specific alternative splicing of tra pre-mRNA. The tra gene encodes a protein that is thought to act in conjunction with the transformer-2 (tra-2) gene product to control the sex-specific processing of doublesex (dsx) pre-mRNA. The bifunctional dsx gene carries out opposite functions in the two sexes, repressing female differentiation in males and repressing male differentiation in females. Here we report the results from an evolutionary approach to investigate tra regulation and function, by isolating the tra-homologous genes from selected Drosophila species, and then using the interspecific DNA sequence comparisons to help identify regions of functional significance. The tra-homologous genes from two Sophophoran subgenus species, Drosophila simulans and Drosophila erecta, and two Drosophila subgenus species, Drosophila hydei and Drosophila virilis, were cloned, sequenced and compared to the D. melanogaster tra gene. This comparison reveals an unusually high degree of evolutionary divergence among the tra coding sequences. These studies also highlight a highly conserved sequence within intron one that probably defines a cis-acting regulator of the sex-specific alternative splicing event.
Subject(s)
Biological Evolution , Drosophila melanogaster/genetics , Transformation, Genetic , Amino Acid Sequence , Animals , Base Sequence , Blotting, Southern , DNA/genetics , Genes, Lethal , Molecular Sequence Data , Nucleic Acid Hybridization , Phenotype , RNA Precursors/genetics , RNA Splicing , RNA, Messenger/genetics , Restriction Mapping , Sequence Homology, Nucleic Acid , Sex Differentiation/genetics , Species Specificity , Transcription, GeneticABSTRACT
Total joint arthroplasty is a common orthopedic procedure and requires prophylactic antibiotic coverage to prevent infections in the operated joint. The antibiotics routinely used for prophylaxis are the cephalosporins. This study compared bone, synovial fluid, and plasma concentrations of ceforanide with cephalothin concentrations in 30 patients undergoing elective total hip or total knee arthroplasty. Ceforanide provided significantly higher plasma concentrations for 61-110 minutes postdose than did cephalothin (p less than 0.025 and p less than 0.005). No difference was noted between the two antibiotics for the bone concentrations in the total hip arthroplasty group; however, cephalothin concentrated to a greater degree in the bone of patients undergoing total knee arthroplasty (p less than 0.05). Cephalothin achieved higher concentrations in the synovial fluid than did ceforanide (p less than 0.05). Both antibiotics were well tolerated and no postoperative infections were noted in either group.
