Techniques for Manipulating Chromosomal Rearrangements and Their Application to DROSOPHILA MELANOGASTER. I. Pericentric Inversions

Techniques have been developed for manipulating pericentric inversions in Drosophila that are based on the lethality of grossly aneuploid zygotes and the existence of recombinationally interconvertible genotypes for any heterozygous inversion complex: males of some of these genotypes will produce only aneuploid sperm, which can be used to rescue complementary aneuploid ova and selectively recover recombinational derivatives of inversions. Markers can be recombined into inversions through a sequence of selected single exchanges, and a novel type of duplication can be synthesized from overlapping inversions that has the characteristics of both insertional and tandem duplications; there are also applications to half-tetrad analyses.——Two cytogenetic screens are developed: (1) the dominant lethality of a large insertional-tandem duplication can be reverted by deletional events that give rise to net deficiencies or duplications, and (2) deficiencies and tandem duplications in proximal regions can be selectively recovered as the results of unequal exchanges within an inversion loop. Recombinants have been recovered between breakpoints separated by distances of as little as fifty bands, arguing against the existence of some small number of sites necessary for the initiation of recombinational pairing. In several instances, hyperploids for four to six numbered divisions were observed to be fertile in both sexes.     

Rib cage distortion during voluntary and involuntary breathing acts

We examined chest wall and rib cage configuration in seven normal subjects during a variety of breathing maneuvers. Magnetometers were used to measure lower rib cage anteroposterior, lower rib cage transverse, upper rib cage anteroposterior, and abdomen anteroposterior diameters. Changes of these diameters were recorded during voluntary maneuvers, rebreathing, reading, and "natural" breathing. Relative motion of the rib cage and abdomen was displayed with the rib cage represented by the product of its lower anteroposterior and transverse diameters. During spontaneous breathing the rib cage and chest wall are near their relaxation configuration. During chemically driven ventilation the chest wall and rib cage progressively depart from this configuration. Much greater distortions of the chest wall and rib cage occurred during some voluntary maneuvers. Additionally, esophageal pressure and gastric pressure were measured during voluntary distortion of the rib cage. Substantial changes in lower rib cage shape occurred during voluntary maneuvers when compared with spontaneous breaths at the same transmural pressure. We conclude that the unitary behavior of the rib cage in normal subjects requires muscle coordination.     

Salutary effects of androstenediol on cardiac function and splanchnic perfusion after trauma-hemorrhage

Recent studies have shown that dehydroepiandrosterone (DHEA) administration after trauma-hemorrhage (T-H) improves cardiovascular function and decreases cytokine production in male animals. Although androstenediol, one of the metabolites of DHEA, is reported to have estrogen-like activity, it remains unknown whether androstenediol per se has any salutary effects on cytokines and cardiovascular function after T-H. To examine this effect, male Sprague-Dawley rats underwent laparotomy and were bled to and maintained at a mean arterial blood pressure of 35-40 mmHg for approximately 90 min. The animals were resuscitated with four times the volume of maximal bleedout volume in the form of Ringer lactate. Androstenediol (1 mg/kg body wt i.v.) or vehicle was administered at the end of resuscitation. Twenty-four hours after resuscitation, cardiac function and organ blood flow were measured by using (85)Sr-microspheres. Circulating levels of nitrate/nitrite and IL-6 were also determined. Cardiovascular function and organ blood flow were significantly depressed after T-H. However, these parameters were restored by androstenediol treatment. The elevated plasma IL-6 levels after T-H were also lowered by androstenediol treatment. In contrast, plasma levels of nitrate/nitrite were the highest in the androstenediol-treated T-H animals. Because androstenediol administration after T-H decreases cytokine production and improves cardiovascular function, this agent appears to be a novel and useful adjunct for restoring the depressed cardiovascular function and for cytokine production in males after adverse circulatory conditions.     

Loss of phylogenetic information in chorion gene families of Bombyx mori gene conversion

The silkmoth chorion has provided a stimulating model for the study of evolution and developmental regulation of gene families. Previous attempts at inferring relationships among chorion sequences have been based on pairwise comparisons of overall similarity, a potentially problematic approach. To remedy this, we identified the alignable regions of low sequence variability and then analyzed this restricted database by parsimony and neighbor-joining methods. At the deepest level, the chorion sequence tree is split into two branches, called "alpha" and "beta." Within each branch, early- and late-expressing genes each constitute monophyletic groups, while the situation with middle-expressing genes remains uncertain. The HcB gene family appears to be the most basal beta-branch group, but this conclusion is qualified because the effect of gene conversion on branching order is unknown. Previous studies by Eickbush and colleagues have strongly suggested that ErA, HcA, and HcB families undergo gene conversion within a gene family, whereas the ErB family does not. The occurrence of conversion correlates with a particular tree structure; namely, branch lengths are much greater at the base of the family than at higher internodes and terminal branches. These observations raise the possibility that chorion gene families are defined by gene conversion events (reticulate evolution) rather than by descent with modification (synapomorphy).      

Total and local impedances of the chest wall up to 10 Hz

To understand how bical mechanical chest wall (CW) properties are related to those of the CW as a whole, we measured esophageal and gastric pressures, CW volume changes (measured with a head-out body plethysmograph), and anteroposterior and transverse CW diameter changes (measured with magnetometers attached to the surface) during sinusoidal forcing at the mouth (2.5% vital capacity, 0.5-10 Hz) in four healthy subjects. Total CW resistance decreased sharply as frequency rose to 3-4 Hz and remained relatively constant at higher frequencies. Total CW reactance became less negative with increasing frequency but showed no tendency to change sign. Above 2 Hz, diameters measured at different locations changed asynchronously between and within the rib cage and abdomen. "Local pathway impedances" (ratios of esophageal or gastric pressure to a rate of diameter change) showed frequency dependence similar to that of the total CW less than 3 Hz. Local pathway impedances increased during contraction of respiratory muscles acting on the pathway. We conclude that 1) total CW behavior is mainly a reflection of its individual local properties at less than or equal to 3 Hz, 2) local impedances within the rib cage or within the abdomen can change independently in some situations, and 3) asynchronies that develop within the CW during forcing greater than 3 Hz suggest that two compartments may be insufficient to describe CW properties from impedance measurements.     

Chest wall motion of infants during spinal anesthesia

To test the extent to which diaphragmatic contraction moves the rib cage in awake supine infants during quiet breathing, we studied chest wall motion in seven prematurely born infants before and during spinal anesthesia for inguinal hernia repair. Infants were studied at or around term (postconceptional age 43 +/- 8 wk). Spinal anesthesia produced a sensory block at the T2-T4 level, with concomitant motor block at a slightly lower level. This resulted in the loss of most intercostal muscle activity, whereas diaphragmatic function was preserved. Rib cage and abdominal displacements were measured with respiratory inductance plethysmography before and during spinal anesthesia. During the anesthetic, outward inspiratory rib cage motion decreased in six infants (P less than 0.02, paired t test); four of these developed paradoxical inward movement of the rib cage during inspiration. One infant, the most immature in the group, had inward movement of the rib cage both before and during the anesthetic. Abdominal displacements increased during spinal anesthesia in six of seven infants (P less than 0.05), suggesting an increase in diaphragmatic motion. We conclude that, in the group of infants studied, outward rib cage movement during awake tidal breathing requires active, coordinated intercostal muscle activity that is suppressed by spinal anesthesia.     

Chest wall impedance partitioned into rib cage and diaphragm-abdominal pathways

We measured chest wall "pathway impedances" (ratios of pressure changes to rates of volume displacement at the surface) with esophageal and gastric balloons and inductance plethysmographic belts around the rib cage and abdomen during forced volume oscillations (5% vital capacity, 0.5-4 Hz) at the mouth of five relaxed, seated subjects. Volume displacements of the total chest wall surface, measured by summing the rib cage and abdominal signals, approximated measurements using volume-displacement, body plethysmography over the entire frequency range. Resistance (R) and elastance (E) of the diaphragm-abdomen pathway were several times greater than those of the rib cage pathway, except at the highest frequencies where diaphragm-abdominal E was small. R and E of the diaphragm-abdomen pathway and of the rib cage pathway showed the same frequency dependencies as that of the total chest wall: R decreased markedly as frequency increased, and E (especially in the diaphragm-abdomen) decreased at the highest frequencies. These results suggest that the chest wall can be reasonably modeled, over the frequency range studied, as a system with two major pathways for displacement. Each pathway seems to exhibit behavior that reflects nonlinear, rate-independent dissipation as well as viscoelastic properties. Impedances of these pathways are useful indexes of changes in chest wall mechanical behavior in different situations.