An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region.

A contiguous sequence of nearly 3 Mb from the genome of Drosophila melanogaster has been sequenced from a series of overlapping P1 and BAC clones. This region covers 69 chromosome polytene bands on chromosome arm 2L, including the genetically well-characterized "Adh region." A computational analysis of the sequence predicts 218 protein-coding genes, 11 tRNAs, and 17 transposable element sequences. At least 38 of the protein-coding genes are arranged in clusters of from 2 to 6 closely related genes, suggesting extensive tandem duplication. The gene density is one protein-coding gene every 13 kb; the transposable element density is one element every 171 kb. Of 73 genes in this region identified by genetic analysis, 49 have been located on the sequence; P-element insertions have been mapped to 43 genes. Ninety-five (44%) of the known and predicted genes match a Drosophila EST, and 144 (66%) have clear similarities to proteins in other organisms. Genes known to have mutant phenotypes are more likely to be represented in cDNA libraries, and far more likely to have products similar to proteins of other organisms, than are genes with no known mutant phenotype. Over 650 chromosome aberration breakpoints map to this chromosome region, and their nonrandom distribution on the genetic map reflects variation in gene spacing on the DNA. This is the first large-scale analysis of the genome of D. melanogaster at the sequence level. In addition to the direct results obtained, this analysis has allowed us to develop and test methods that will be needed to interpret the complete sequence of the genome of this species. Before beginning a Hunt, it is wise to ask someone what you are looking for before you begin looking for it. Milne 1926

Changes in conduction within the diffuse sinoatrial node of the chicken following premature atrial stimulation.

Premature atrial stimulation was used to estimate sinoatrial conduction within the diffuse sinoatrial node of the bird (chicken), and compare its conduction with that reported for mammals. While sinoatrial conduction could not be determined in the chicken because reset did not occur, the premature wavefront did have an effect on the sinoatrial node because the recovery interval following the premature stimulus became less than compensatory with shortening of the premature stimulus interval. This less than compensatory non-reset recovery interval is interpreted as a conduction dependent response in which the intrinsic wavefront leading to the first recovery atrial activation conducts out of the node faster than normal. This conduction dependent recovery interval is seen infrequently in mammals (rabbit, dog and man). The absence of reset and the presence of a less than compensatory non-reset response in the chicken suggests that while the general organization of the sinoatrial node of the chicken is similar to that in mammals, a larger transitional cell network in the chicken prevents a premature wavefront from reaching the pacemaker cells and resetting them.

Effect of cervical vagal stimulation on chicken heart rate and atrioventricular conduction.

The effects of supramaximal stimulation of the right and left cervical vagi on heart rate, pacemaker localization, and atrioventricular (AV) conduction were investigated in 15 anesthetized open-chest chickens before and after atropine sulfate. Epicardial bipolar electrograms were recorded from selected atrial sites and right ventricle. A back lead electrocardiogram was also recorded. The effect of stimulation on atrioventricular conduction was evaluated during pacing from one of the right atrial recording sites. Supramaximal stimulation of either cervical vagus produced bradycardia but not cardiac arrest. Heart rate was reduced from an average spontaneous rate of 282 +/- 13 (SE)/min to 161 +/- 13/min with stimulation of the right and left cervical vagus. Pacemaker shifts occurred in over 50% of the vagal stimulations. The most frequent shift occurred to the lower AV node or ventricles. Pacemaker shifts to the AV junctional region producing almost simultaneous activation of the atria and ventricles were not observed. Vagal stimulation during atrial pacing produced minimal prolongation in AV conduction time [right vagus, 13 +/- 3 (SE) ms; left vagus, 8 +/- 2 ms]. Second and third degree heart blocks were not observed during pacing. Vagal stimulation after atropine indicates that the cervical vagi do not contain sympathetic fibers going to pacemaker or AV conduction tissues.

Real-time analysis of hippocampal neural activity in the intervals between interictal spikes.

Previously the electroencephalogram (EEG) was modeled as consisting of faster, smaller waves superimposed on larger, slower waves. The intent of this study is to modify the program to sample neural activity over specific intervals of time following detection of a distinct wave pattern. The use of conditional sampling is illustrated by considering wave detection following epileptic interictal spikes in the rabbit hippocampus. To create an epileptic focus, small pellets of sodium penicillin suspended in agar were placed on the rabbit hippocampus. This produced regularly recurring, spontaneous, large amplitude discharges, or interictal spikes, at the site of application. Following detection of an interictal spike, the program delayed the onset of a sample period for either 1.0 s or 6.0 s. The neural activity was then sampled for 5.1 s, and fast and slow waves were detected over the sample period. The frequency distribution of waves in four of these 5.1 s intervals was calculated. Comparison of the frequency distributions following the 1.0 s and 6.0 s delays showed no discernible differences. The data illustrate that not all types of neural activity are markedly modified by interictal spikes and suggest that hippocampal cellular populations generate similar waves 1.0 s and 6.0 s after such a spike. Moreover, this experiment illustrates adaptation of the program to sample activity over a limited period of time following detection of a specific cortical waveform.