Screening for mutations in exon 4 of the LDL receptor gene in a German population with severe hypercholesterolemia.

A group of 218 patients with severe hypercholesterolemia (LDL cholesterol > 260 mg/dl) living in the Cologne area were screened for mutations in the 3 half of exon 4 of the low density lipoprotein (LDL) receptor gene by the single-strand conformation polymorphism (SSCP) method. The analysed fragment was 242 bp in length and comprised approximately 6% of the coding region. In 11 patients an abnormal SSCP pattern was observed. Two of the abnormal fragment patterns were identical. The results of the SSCP screening could be confirmed by direct DNA sequencing. Three of the ten different mutations were previously described (3 bp deletion: codon 197; Asp200-->Gly; Glu207-->stop). Of the newly identified mutations there were two deletions, two insertions, one combined insertion and deletion mutation and two single base pair substitutions [1 bp deletion: G in codon 197; 37 bp deletion: T in codon 196-208 or AT in 196-207 and GA in codon 208; 18 bp insertion: codon 201-206; 8 bp insertion: codon 155-156 and GA in codon 157; 6 bp insertion (codon 196-197) and 5 bp deletion (codon 199, C in codon 198 and G in codon 198 or 200); Asp200-->Tyr; Asp203-->Val]. The 8-bp insertion was detected in a second unrelated individual. The analysis of the functional consequences of the mutations indicates that all mutations were causative of the LDL cholesterol elevation.

Effect of photoperiod on metabolic rate in a subtropical population of Drosophila melanogaster.

1. Descendents of a Florida, U.S.A. population of Drosophila melanogaster were reared under short (8 hr light: 16 hr dark) and long (16 hr light: 8 hr dark) photoperiods. 2. Flies reared under short photoperiods had higher rates of metabolism at 21 degrees C. 3. Because genetic background (iso-female line) affects metabolic rates, statistical control through analysis of covariance was necessary to isolate the effects of photoperiod on metabolic rates. 4. These results on a subtropical population of D. melanogaster are similar to those found on a temperate population of the same species.

Seasonal change in metabolic rate of Drosophila simulans.

1. Second-generation descendents of wild-caught female Drosophila simulans Sturtevant collected at different seasons from Gainesville, Florida, USA, were reared under a constant temperature and food level but with seasonally variable photoperiods. 2. Body weight and metabolic rate, after adjustment to a common body weight, were higher in descendents of flies collected in fall and winter. 3. Temperature sensitivity (Q10) of metabolic rate was also related to season: higher Q10 values were associated with seasons of increasing temperatures and lower Q10 values were associated with seasons of decreasing temperatures. 4. These metabolic characteristics may be adaptive in enhancing activity at lower temperatures and conserving energy at higher temperatures.

Effects of exposing Drosophila melanogaster parents to ethanol on expression of vestigial in their progeny.

When parental Drosophila melanogaster were chronically exposed at 28 degrees C or 24 degrees C to ethanol during their larval and pupal stages of development, their progeny, produced when parents were 5-16-day-old adults, showed modified expression of vestigial alleles in heterozygous and homozygous combinations. Parental alcohol effects were dependent on parental rearing temperature. We conclude that parental environment (alcohol, temperature) causes heritable but transitory changes in progeny phenotype that are elicited by exposure of germ cells to alcohol.

Apnoeic diving safety - experimental approaches to oxygen augmentation.

Oxygen augmentation during ascent for distressed apnoeic divers has recently been both advocated and criticized. Experiments involving 111 apnoeic divers have been conducted, shedding light on diving safety when oxygen augmentation is used at the onset of the apnoeic black-out, and are summarized in this report. It is maintained that black-out sets in gradually during ascent, taking the form of progressive tunnel vision, leaving scope for rational action by a distressed diver before complete loss of consciousness. By triggering a device (e.g. a 50 - 100 ml syringe) loaded with oxygen by means of pressure or otherwise at the onset of symptoms of hypoxic black-out during a 10 m dive, unconsciousness is believed to be delayed. This is because it takes a diver 12 seconds to rise to the surface from 10 m, while the lung-brain circulation time, inferred from textbook lung-ear circulation times for oxyhaemoglobin, is approximately 5.2 seconds. Since the oxygen is injected into the trachea by force and because of simulated involuntary ventilatory activity which dynamically mixes mouth and alveolar gas during apnoeic diving stress, the injected oxygen is believed to be quickly delivered at the alveoli. Such gas injection was shown to raise the amount of oxygen available to the diver by 25 - 50%. Intrathoracic pressure increases could ensure delivery of enough oxygen to the capillaries to delay unconsciousness. Recommendations for using the syringe at present apply only to 10 m dives and do not exclude use of other safety devices currently in use by divers or envisaged for their safety.

A model of functional epistasis and linkage disequilibrium in populations with overlapping generations.

A model of functional epistasis is proposed in which it is assumed that coupling and repulsion genotypes differ in metabolic efficiency and thus in development time and net fecundity. The implications of this model are investigated for iteroparous populations with fluctuating rates of increase. It is found that the fluctuations in rate of increase can lead to large fluctuations in gamete frequency and D, the coefficient of linkage disequilibrium, but that D will almost always have a value of zero at some point during the populations' demographic cycle. Some of the model populations would be expected to be in a state of linkage disequilibrium only fleetingly: others would exhibit D-cycles interpretable as random fluctuation. Implications of the model for interpretations of existing data on linkage disequilibrium among enzyme loci in Drosophila are discussed.

Biology of a duplicate gene system with glucose 6-phosphate dehydrogenase activity in Drosophila melanogaster: genetic analysis and differences in fitness components and reaction to environmental parameters among Zw genotypes.

There are two structural forms of glucose 6-phosphate dehydrogenase activity in Drosophila melanogaster. Whether one or the other or both show in vitro (and probably in vivo) activity depends on the genotype of a sex-linked locus (Zw). In this article, the relative fittnesses of heterozygotes (with both electromorphs active) and homozygotes (with activity demonstrable for only one or the other electromorph) for the Zw locus are described. It is shown that the relative fitness of heterozygotes increases with increase in population density, or degree of crowding and trophic stress, and that the mean development times of Zw heterozygotes are lower than those of the Zw homozygotes. In addition, and perhaps accounting for the fitness and viability excess of the heterozygotes, one set of evidence strongly suggests that they are better buffered against trophic stress than the homozygotes.