Traumatic aortic rupture after blunt trauma.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
F R Jackson
Publications and source records attributed to F R Jackson.
Transthoracic vagotomy for recurrent peptic ulcers.
Explore the source record for details and available documents.
Peptic Ulcer↗
Two types of mutants affecting voltage-sensitive sodium channels in Drosophila melanogaster.
Voltage-sensitive sodium channels have a key role in the genesis of propagated action potentials. Mutations that affect these channels might be used like specific pharmacological agents in studies of channel structure and regulation. We have found that mutations which cause a reversible, temperature-induced paralysis in the fruit fly Drosophila melanogaster often affect the voltage-sensitive sodium channel. Using 3H-saxitoxin binding to membrane preparations, we have now identified two types of presumptive sodium channel mutants. One mutation, seizurets-2 (seits-2), appears to alter saxitoxin-binding sites structurally. The second, no-action-potential (napts) (refs 5, 6), reduces the number of saxitoxin-binding sites, but appears not to alter the receptor structure.
Animals↗
Restoration of circadian behavioural rhythms by gene transfer in Drosophila.
The per locus of Drosophila melanogaster has a fundamental role in the construction or maintenance of a biological clock. Three classes of per mutations have been identified: per mutants have circadian behavioural rhythms with a 29-h rather than a 24-h period, pers mutants have short-period rhythms of 19 h, and per mutants have no detectable circadian rhythms. Each of these mutations has a corresponding influence on the 55-s periodicity of male courtship song. Long- and short-period circadian rhythm phenotypes can also be obtained by altering the dosage of the wild-type gene: for example, females carrying only one dose of this X-linked gene have circadian rhythms with periodicities about 1 h longer than those carrying two doses. In a previous report, cloned DNA was used to localize several chromosomal rearrangement breakpoints that alter per locus function. The rearrangements all affected a 7-kilobase (kb) interval that encodes a 4.5-kb poly(A)+ RNA. We report here that when a 7.1-kb fragment from a per+ fly, including the sequences encoding the 4.5-kb transcript, is introduced into the genome of a per (arrhythmic) fly by P element-mediated transformation, circadian rhythmicity of behaviour such as eclosion and locomotor activity is restored. The transforming DNA complements per locus deletions and is transcribed, forming a single 4.5-kb poly(A)+ RNA comparable to that produced by wild-type flies.
Animals↗
An unusual coding sequence from a Drosophila clock gene is conserved in vertebrates.
The per locus has a fundamental involvement in the expression of biological rhythms in Drosophila. Mutations at this locus can shorten, lengthen or eliminate a variety of rhythmic activities that range from circadian behaviours, exemplified by eclosion and locomotor activities, to short-period behaviour such as the 55-s rhythm of courtship song. DNA from the per locus has been cloned, and we have used P-element-mediated DNA transformation to establish that a 7.1-kilobase(kb) HindIII fragment contains a functional copy of the gene. This transforming DNA contains a single transcription unit which gives rise to a 4.5-kb poly(A)+ RNA. Here we report the results of a search for sequences homologous to the per locus DNA in the genomic DNA of several species of vertebrates. An unusual, tandemly repeated sequence forming a portion of the 4.5-kb per transcript is homologous to DNA in chicken, mouse and man. Cloned DNAs from the mouse and Drosophila are related by long, uninterrupted tandem repetitions of the sequence ACNGGN. At the per locus, these tandem repeats are predicted to code for poly(Thr-Gly) tracts up to 48 amino acids long. These repeated sequences are also transcribed in the mouse. Several long tracts of poly(Thr-Gly) appear to be encoded by DNA cloned from the mouse.
Amino Acid Sequence↗
Product of per locus of Drosophila shares homology with proteoglycans.
Genes controlling biological rhythms have been identified in Drosophila. The best characterized of these genes is called period (per). Although wild-type flies have daily (circadian) rhythms with a periodicity of approximately 24 h, pers and per1 mutants have 19-h and 29-h rhythms, respectively, and pero mutants are arrhythmic. The pers mutation also enhances the sensitivity of the circadian clock to resetting by light stimuli, and all three types of per mutations affect a much shorter period ultradian rhythm, the 55-s rhythm of the Drosophila courtship song. A fragment of DNA of approximately 7 kilobases (kb) encoding a 4.5-kb poly(A)+ RNA restores rhythmicity when transduced into Drosophila carrying mutations or chromosomal deletions of the per locus. Here we report the sequence of this biologically active segment of DNA. The transcription unit that encodes the 4.5-kb RNA has been mapped, permitting a conceptual translation of a protein of 1,127 amino acids. Several abnormal phenotypes characterized by long-period rhythms are associated with changes in the sequence of untranslated portions of the transcription unit. The structure of some segments of the predicted protein suggests that it is a proteoglycan.
Amino Acid Sequence↗
Changes in abundance or structure of the per gene product can alter periodicity of the Drosophila clock.
The period (per) locus, which controls biological rhythms in Drosophila, was originally defined by three chemically induced mutations. Flies carrying the pero mutation were arrhythmic, whereas pers and perl mutants had circadian behavioural rhythms with 19-hour and 29-hour periodicities, respectively. Wild-type flies have 24-hour rhythms. Here we compare the per locus DNA sequences of the three mutants with the parental wild-type. The pers and perl mutations lead to amino-acid substitutions, whereas pero introduces an early translation stop (amber). The results indicate that the protein product of per controls biological rhythms. We also report that the abundance of this protein may set the pace of the Drosophila clock. Although circadian rhythms are restored when arrhythmic (per-) Drosophila are transformed with per locus DNA, flies receiving identical transforming DNA segments can produce rhythms with periods that differ by more than 12 hours. Transcription studies reveal a tenfold variation in the level of per RNA among transformed lines. Levels of per RNA are inversely correlated with period length, so that flies with lowest levels of the per product have slow-running biological clocks. On the basis of the combined studies we suggest that perl and pers mutants produce hypoactive and hyperactive per proteins, respectively.
Amino Acid Sequence↗